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Chlamydia infections associated with more than a doubling of ovarian cancer risk
Pelvic inflammatory disease caused by chlamydia appears to significantly increase the risk of ovarian cancer, according to research to be presented at the annual meeting of the American Association for Cancer Research.
The finding, replicated in two large databases, suggests that promptly treating the infection might reduce the lifetime risk of developing ovarian cancer, Britton Trabert, PhD, said during a press briefing held in advance of the meeting.
The study portends both promise and challenge, according to Elaine R. Mardis, PhD, who comoderated the session.
“Ovarian cancer is typically diagnosed at a late stage and therefore has a poor prognosis,” said Dr. Mardis of The Nationwide Hospital, Columbus, Ohio. “Chlamydia will be an important point of study here, both because of the frequency of this infection, and because it is quite difficult to detect, due to its asymptomatic nature. But the most important take-home point is that we might be able to go a long way in terms of preventing ovarian cancer by routinely screening for infective agents.”
Pelvic inflammatory disease is known to be associated with ovarian cancer, and chlamydia is a leading cause of the disease, noted Dr. Trabert. “But chlamydia infections can be asymptomatic and persist for months or even years, so ascertainment of past chlamydia infections is challenging.”
To investigate the potential link between these infections and ovarian cancer, Dr. Trabert and her colleagues examined associations between antibodies to several infectious agents, including chlamydia, in two large ovarian cancer databases: a population-based case/control study in Poland and a case-control study nested into the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
The researchers screened for antibodies to chlamydia, Mycoplasma genitalium, Epstein-Barre virus, human papillomavirus, herpes simplex virus-1 and -2, polyomavirus, hepatitis B and C, and cytomegalovirus. The chlamydia antibody selected was plasmid-encoded Pgp3 protein, considered the gold standard measurement for prior or existing chlamydia infections.
The patient cohorts comprised 278 cases vs. 556 controls from the Polish study, and 160 cases vs. 159 controls from the PLCO study. Serum samples were collected at the time of ovarian cancer diagnosis in the Polish cohort, and before diagnosis in the PLCO cohort.
Dr. Trabert presented odds ratios for a Pgp3 antibody titer cut point indicative of past chlamydia infection, and a “more stringent” higher cut point indicative of current or chronic infection. She and her colleagues found statistically significant associations for each cut point in both studies.
In the Polish cohort, the lower Pgp3 cut point was associated with a 63% increased risk of ovarian cancer (odds ratio, 1.63). The higher cut point was associated with a doubling of risk (OR, 2.0).
In the PLCO cohort, the lower cut point was associated with a 43% increased risk (OR, 1.43). The higher cut point more than doubled the risk of ovarian cancer (OR, 2.25).
Neither cohort showed any significant association of ovarian cancer with any of the other antibodies, Dr. Trabert said.
The NCI Intramural Research Program supported the study. Dr. Trabert and her colleagues declared no conflicts of interest.
SOURCE: Trabert et al. Abstract 4942.
Pelvic inflammatory disease caused by chlamydia appears to significantly increase the risk of ovarian cancer, according to research to be presented at the annual meeting of the American Association for Cancer Research.
The finding, replicated in two large databases, suggests that promptly treating the infection might reduce the lifetime risk of developing ovarian cancer, Britton Trabert, PhD, said during a press briefing held in advance of the meeting.
The study portends both promise and challenge, according to Elaine R. Mardis, PhD, who comoderated the session.
“Ovarian cancer is typically diagnosed at a late stage and therefore has a poor prognosis,” said Dr. Mardis of The Nationwide Hospital, Columbus, Ohio. “Chlamydia will be an important point of study here, both because of the frequency of this infection, and because it is quite difficult to detect, due to its asymptomatic nature. But the most important take-home point is that we might be able to go a long way in terms of preventing ovarian cancer by routinely screening for infective agents.”
Pelvic inflammatory disease is known to be associated with ovarian cancer, and chlamydia is a leading cause of the disease, noted Dr. Trabert. “But chlamydia infections can be asymptomatic and persist for months or even years, so ascertainment of past chlamydia infections is challenging.”
To investigate the potential link between these infections and ovarian cancer, Dr. Trabert and her colleagues examined associations between antibodies to several infectious agents, including chlamydia, in two large ovarian cancer databases: a population-based case/control study in Poland and a case-control study nested into the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
The researchers screened for antibodies to chlamydia, Mycoplasma genitalium, Epstein-Barre virus, human papillomavirus, herpes simplex virus-1 and -2, polyomavirus, hepatitis B and C, and cytomegalovirus. The chlamydia antibody selected was plasmid-encoded Pgp3 protein, considered the gold standard measurement for prior or existing chlamydia infections.
The patient cohorts comprised 278 cases vs. 556 controls from the Polish study, and 160 cases vs. 159 controls from the PLCO study. Serum samples were collected at the time of ovarian cancer diagnosis in the Polish cohort, and before diagnosis in the PLCO cohort.
Dr. Trabert presented odds ratios for a Pgp3 antibody titer cut point indicative of past chlamydia infection, and a “more stringent” higher cut point indicative of current or chronic infection. She and her colleagues found statistically significant associations for each cut point in both studies.
In the Polish cohort, the lower Pgp3 cut point was associated with a 63% increased risk of ovarian cancer (odds ratio, 1.63). The higher cut point was associated with a doubling of risk (OR, 2.0).
In the PLCO cohort, the lower cut point was associated with a 43% increased risk (OR, 1.43). The higher cut point more than doubled the risk of ovarian cancer (OR, 2.25).
Neither cohort showed any significant association of ovarian cancer with any of the other antibodies, Dr. Trabert said.
The NCI Intramural Research Program supported the study. Dr. Trabert and her colleagues declared no conflicts of interest.
SOURCE: Trabert et al. Abstract 4942.
Pelvic inflammatory disease caused by chlamydia appears to significantly increase the risk of ovarian cancer, according to research to be presented at the annual meeting of the American Association for Cancer Research.
The finding, replicated in two large databases, suggests that promptly treating the infection might reduce the lifetime risk of developing ovarian cancer, Britton Trabert, PhD, said during a press briefing held in advance of the meeting.
The study portends both promise and challenge, according to Elaine R. Mardis, PhD, who comoderated the session.
“Ovarian cancer is typically diagnosed at a late stage and therefore has a poor prognosis,” said Dr. Mardis of The Nationwide Hospital, Columbus, Ohio. “Chlamydia will be an important point of study here, both because of the frequency of this infection, and because it is quite difficult to detect, due to its asymptomatic nature. But the most important take-home point is that we might be able to go a long way in terms of preventing ovarian cancer by routinely screening for infective agents.”
Pelvic inflammatory disease is known to be associated with ovarian cancer, and chlamydia is a leading cause of the disease, noted Dr. Trabert. “But chlamydia infections can be asymptomatic and persist for months or even years, so ascertainment of past chlamydia infections is challenging.”
To investigate the potential link between these infections and ovarian cancer, Dr. Trabert and her colleagues examined associations between antibodies to several infectious agents, including chlamydia, in two large ovarian cancer databases: a population-based case/control study in Poland and a case-control study nested into the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial.
The researchers screened for antibodies to chlamydia, Mycoplasma genitalium, Epstein-Barre virus, human papillomavirus, herpes simplex virus-1 and -2, polyomavirus, hepatitis B and C, and cytomegalovirus. The chlamydia antibody selected was plasmid-encoded Pgp3 protein, considered the gold standard measurement for prior or existing chlamydia infections.
The patient cohorts comprised 278 cases vs. 556 controls from the Polish study, and 160 cases vs. 159 controls from the PLCO study. Serum samples were collected at the time of ovarian cancer diagnosis in the Polish cohort, and before diagnosis in the PLCO cohort.
Dr. Trabert presented odds ratios for a Pgp3 antibody titer cut point indicative of past chlamydia infection, and a “more stringent” higher cut point indicative of current or chronic infection. She and her colleagues found statistically significant associations for each cut point in both studies.
In the Polish cohort, the lower Pgp3 cut point was associated with a 63% increased risk of ovarian cancer (odds ratio, 1.63). The higher cut point was associated with a doubling of risk (OR, 2.0).
In the PLCO cohort, the lower cut point was associated with a 43% increased risk (OR, 1.43). The higher cut point more than doubled the risk of ovarian cancer (OR, 2.25).
Neither cohort showed any significant association of ovarian cancer with any of the other antibodies, Dr. Trabert said.
The NCI Intramural Research Program supported the study. Dr. Trabert and her colleagues declared no conflicts of interest.
SOURCE: Trabert et al. Abstract 4942.
FROM THE AACR ANNUAL MEETING
Key clinical point: Chlamydia infections appear to increase the risk of ovarian cancer.
Major finding: The presence of an antibody to chlamydia increased the chance of ovarian cancer by up to 2.25-fold (OR 2.25).
Study details: The cohorts comprised 278 cases vs. 556 controls from a Polish study, and 160 cases vs. 159 controls from a U.S. study.
Disclosures: The NCI Intramural Research Program supported the study. The researchers declared no conflicts of interest.
Source: Trabet et al. Abstract 4942.
Variants in one gene account for 7% of juvenile myoclonic epilepsy cases
An extremely rare genetic variant that affects the maturation, migration, and death of neurons appears to be responsible for about 7% of cases of juvenile myoclonic epilepsy.
Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD, of the University of California, Los Angeles, and her colleagues reported in the March 15 issue of the New England Journal of Medicine.
“We report striking variation with respect to epilepsy phenotypes both within and among families,” the team wrote. “Of 34 affected nonproband family members, 5 (15%) had juvenile myoclonic epilepsy, 10 (29%) had myoclonic-tonic-clonic seizures, 4 (12%) had pyknoleptic petit mal seizures alone or with myoclonic-tonic-clonic seizures, 4 (12%) had febrile seizures alone or with absence seizures or myoclonias, and 11 (32%) were clinically asymptomatic but had polyspikes or focal spikes on EEG. These results strongly suggest that ICK is pleiotropic ... and that epistatic loci with different genes are present in affected family members and interact with ICK and contribute to pleiotropism and clinical heterogeneity.”
Despite the misnomer of intestinal-cell kinase, ICK “is ubiquitous and is expressed in all tissues,” senior study author Antonio Delgado-Escueta, MD, professor of neurology at UCLA, noted in an interview. He said the brain dysplasia, or microdysgenesis, that occurs in patients with juvenile myoclonic epilepsy (JME) “is very subtle, diagnosed mainly microscopically, and has neuronal cells that migrated from periventricular zones to the wrong places in wrong layers of the cortical gray matter and even the white matter of the brain. The cells can also be abnormally large and bunch up as a thicker gray matter. On voxel-based brain MRI ... focal thickenings of these abnormally migrated cells can also be partly explained by decreased pruning of cells and circuits (apoptosis).”
The gene encoding for ICK is located close to EFHC1 on chromosome 6p12. EFHC1, which encodes for a calcium-binging protein, has been implicated in JME. Dr. Bailey and her colleagues examined whether several genes in close proximity to EFHC1 also influenced that risk.
The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study from the databank analyzed information from 334 families with genetic generalized epilepsies. Among these, 310 patients had adolescent-onset myoclonic seizures and polyspike waves, or had a diagnosis of JME.
The team first performed an exome-wide analysis of four affected members of a large family with genetic JME. They observed the same variants in all four patients, then ran the screen in all 37 family members. Next, they screened these candidate genes in all 334 of the GENESS families and calculated risk scores for JME.
A linkage analysis confirmed two candidate genes on chromosome 6p12.1. Further analyses pinpointed a single variant: K305T on the ICK gene. This was present in each of the 12 affected members and 3 unaffected members of the initial family examined. Of those affected, three had JME, two had myoclonic-tonic-clonic convulsions only, two had febrile convulsions plus childhood absence seizures or neonatal myoclonus, one had febrile convulsions only, and four had polyspikes on EEG and were clinically asymptomatic.
“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.
ICK variants were also present in 24 of the 310 database patients who had JME (8%). Of these, nine belonged to families with other affected members. The team tested 24 ICK variants for pathogenicity and determined that 13 exerted significant JME risk, with odds ratios exceeding 5.0.
When the team looked for these 24 variants in the Genome Aggregation Database (gnomAD), the found that 12 were present but extremely rare, and 8 were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. Interestingly, that variant was a benign polymorphism in Africans.
Dr. Bailey and her colleagues thus concluded that 21 ICK variants accounted for 7% of the JME among the 310 cases examined.
The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice under light sedation displayed muscle movements similar to human myoclonic seizures that occur upon awakening. These mice also displayed diffuse polyspike brain waves on EEG recordings.
“The data we obtained through the use of electroporated slices of mouse brain support the conclusion that those pathogenic variants in ICK cause 7% of cases of juvenile myoclonic epilepsy by disrupting mitosis, neuroblast migration, and apoptosis,” they concluded.
The study was funded by a number of private and public grants from within the United States and other countries. Several authors are coholders of patents on EFHC1-based diagnostic and therapeutics that have been licensed to Athena Diagnostics. Several authors also reported receiving honoraria from various pharmaceutical companies.
SOURCE: Bailey J et al. N Engl J Med. 2018;378:1018-28
An extremely rare genetic variant that affects the maturation, migration, and death of neurons appears to be responsible for about 7% of cases of juvenile myoclonic epilepsy.
Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD, of the University of California, Los Angeles, and her colleagues reported in the March 15 issue of the New England Journal of Medicine.
“We report striking variation with respect to epilepsy phenotypes both within and among families,” the team wrote. “Of 34 affected nonproband family members, 5 (15%) had juvenile myoclonic epilepsy, 10 (29%) had myoclonic-tonic-clonic seizures, 4 (12%) had pyknoleptic petit mal seizures alone or with myoclonic-tonic-clonic seizures, 4 (12%) had febrile seizures alone or with absence seizures or myoclonias, and 11 (32%) were clinically asymptomatic but had polyspikes or focal spikes on EEG. These results strongly suggest that ICK is pleiotropic ... and that epistatic loci with different genes are present in affected family members and interact with ICK and contribute to pleiotropism and clinical heterogeneity.”
Despite the misnomer of intestinal-cell kinase, ICK “is ubiquitous and is expressed in all tissues,” senior study author Antonio Delgado-Escueta, MD, professor of neurology at UCLA, noted in an interview. He said the brain dysplasia, or microdysgenesis, that occurs in patients with juvenile myoclonic epilepsy (JME) “is very subtle, diagnosed mainly microscopically, and has neuronal cells that migrated from periventricular zones to the wrong places in wrong layers of the cortical gray matter and even the white matter of the brain. The cells can also be abnormally large and bunch up as a thicker gray matter. On voxel-based brain MRI ... focal thickenings of these abnormally migrated cells can also be partly explained by decreased pruning of cells and circuits (apoptosis).”
The gene encoding for ICK is located close to EFHC1 on chromosome 6p12. EFHC1, which encodes for a calcium-binging protein, has been implicated in JME. Dr. Bailey and her colleagues examined whether several genes in close proximity to EFHC1 also influenced that risk.
The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study from the databank analyzed information from 334 families with genetic generalized epilepsies. Among these, 310 patients had adolescent-onset myoclonic seizures and polyspike waves, or had a diagnosis of JME.
The team first performed an exome-wide analysis of four affected members of a large family with genetic JME. They observed the same variants in all four patients, then ran the screen in all 37 family members. Next, they screened these candidate genes in all 334 of the GENESS families and calculated risk scores for JME.
A linkage analysis confirmed two candidate genes on chromosome 6p12.1. Further analyses pinpointed a single variant: K305T on the ICK gene. This was present in each of the 12 affected members and 3 unaffected members of the initial family examined. Of those affected, three had JME, two had myoclonic-tonic-clonic convulsions only, two had febrile convulsions plus childhood absence seizures or neonatal myoclonus, one had febrile convulsions only, and four had polyspikes on EEG and were clinically asymptomatic.
“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.
ICK variants were also present in 24 of the 310 database patients who had JME (8%). Of these, nine belonged to families with other affected members. The team tested 24 ICK variants for pathogenicity and determined that 13 exerted significant JME risk, with odds ratios exceeding 5.0.
When the team looked for these 24 variants in the Genome Aggregation Database (gnomAD), the found that 12 were present but extremely rare, and 8 were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. Interestingly, that variant was a benign polymorphism in Africans.
Dr. Bailey and her colleagues thus concluded that 21 ICK variants accounted for 7% of the JME among the 310 cases examined.
The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice under light sedation displayed muscle movements similar to human myoclonic seizures that occur upon awakening. These mice also displayed diffuse polyspike brain waves on EEG recordings.
“The data we obtained through the use of electroporated slices of mouse brain support the conclusion that those pathogenic variants in ICK cause 7% of cases of juvenile myoclonic epilepsy by disrupting mitosis, neuroblast migration, and apoptosis,” they concluded.
The study was funded by a number of private and public grants from within the United States and other countries. Several authors are coholders of patents on EFHC1-based diagnostic and therapeutics that have been licensed to Athena Diagnostics. Several authors also reported receiving honoraria from various pharmaceutical companies.
SOURCE: Bailey J et al. N Engl J Med. 2018;378:1018-28
An extremely rare genetic variant that affects the maturation, migration, and death of neurons appears to be responsible for about 7% of cases of juvenile myoclonic epilepsy.
Variants of the intestinal-cell kinase gene (ICK) occurred in 12 members of a family affected by the disorder and were confirmed in 22 of 310 additional patients, Julia N. Bailey, PhD, of the University of California, Los Angeles, and her colleagues reported in the March 15 issue of the New England Journal of Medicine.
“We report striking variation with respect to epilepsy phenotypes both within and among families,” the team wrote. “Of 34 affected nonproband family members, 5 (15%) had juvenile myoclonic epilepsy, 10 (29%) had myoclonic-tonic-clonic seizures, 4 (12%) had pyknoleptic petit mal seizures alone or with myoclonic-tonic-clonic seizures, 4 (12%) had febrile seizures alone or with absence seizures or myoclonias, and 11 (32%) were clinically asymptomatic but had polyspikes or focal spikes on EEG. These results strongly suggest that ICK is pleiotropic ... and that epistatic loci with different genes are present in affected family members and interact with ICK and contribute to pleiotropism and clinical heterogeneity.”
Despite the misnomer of intestinal-cell kinase, ICK “is ubiquitous and is expressed in all tissues,” senior study author Antonio Delgado-Escueta, MD, professor of neurology at UCLA, noted in an interview. He said the brain dysplasia, or microdysgenesis, that occurs in patients with juvenile myoclonic epilepsy (JME) “is very subtle, diagnosed mainly microscopically, and has neuronal cells that migrated from periventricular zones to the wrong places in wrong layers of the cortical gray matter and even the white matter of the brain. The cells can also be abnormally large and bunch up as a thicker gray matter. On voxel-based brain MRI ... focal thickenings of these abnormally migrated cells can also be partly explained by decreased pruning of cells and circuits (apoptosis).”
The gene encoding for ICK is located close to EFHC1 on chromosome 6p12. EFHC1, which encodes for a calcium-binging protein, has been implicated in JME. Dr. Bailey and her colleagues examined whether several genes in close proximity to EFHC1 also influenced that risk.
The investigators drew data from the GENESS (Genetic Epilepsies Studies) consortium, which has study sites in the United States, Mexico, Honduras, Brazil, and Japan. The current study from the databank analyzed information from 334 families with genetic generalized epilepsies. Among these, 310 patients had adolescent-onset myoclonic seizures and polyspike waves, or had a diagnosis of JME.
The team first performed an exome-wide analysis of four affected members of a large family with genetic JME. They observed the same variants in all four patients, then ran the screen in all 37 family members. Next, they screened these candidate genes in all 334 of the GENESS families and calculated risk scores for JME.
A linkage analysis confirmed two candidate genes on chromosome 6p12.1. Further analyses pinpointed a single variant: K305T on the ICK gene. This was present in each of the 12 affected members and 3 unaffected members of the initial family examined. Of those affected, three had JME, two had myoclonic-tonic-clonic convulsions only, two had febrile convulsions plus childhood absence seizures or neonatal myoclonus, one had febrile convulsions only, and four had polyspikes on EEG and were clinically asymptomatic.
“These results genetically implicated K305T as an autosomal dominant, possibly disease-causing trait,” the authors noted.
ICK variants were also present in 24 of the 310 database patients who had JME (8%). Of these, nine belonged to families with other affected members. The team tested 24 ICK variants for pathogenicity and determined that 13 exerted significant JME risk, with odds ratios exceeding 5.0.
When the team looked for these 24 variants in the Genome Aggregation Database (gnomAD), the found that 12 were present but extremely rare, and 8 were absent. They also found an additional ICK variant in a Mexican patient who was in gnomAD. Interestingly, that variant was a benign polymorphism in Africans.
Dr. Bailey and her colleagues thus concluded that 21 ICK variants accounted for 7% of the JME among the 310 cases examined.
The team also conducted a series of in vitro and in vivo mouse experiments. They determined that ICK variants impaired the migration of neuronal progenitor cells and lowered their mitotic index. ICK transgenic mice under light sedation displayed muscle movements similar to human myoclonic seizures that occur upon awakening. These mice also displayed diffuse polyspike brain waves on EEG recordings.
“The data we obtained through the use of electroporated slices of mouse brain support the conclusion that those pathogenic variants in ICK cause 7% of cases of juvenile myoclonic epilepsy by disrupting mitosis, neuroblast migration, and apoptosis,” they concluded.
The study was funded by a number of private and public grants from within the United States and other countries. Several authors are coholders of patents on EFHC1-based diagnostic and therapeutics that have been licensed to Athena Diagnostics. Several authors also reported receiving honoraria from various pharmaceutical companies.
SOURCE: Bailey J et al. N Engl J Med. 2018;378:1018-28
FROM NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point:
Major finding: ICK variants account for 7% of JME cases.
Study details: Genetic studies comprising one family and 310 epilepsy cases in a database.
Disclosures: The study was funded by a number of private and public grants from within the United States and other countries. Several authors are coholders of patents on EFHC1-based diagnostic and therapeutics that have been licensed to Athena Diagnostics. Several authors also reported receiving honoraria from various pharmaceutical companies.
Source: Bailey J et al. N Engl J Med. 2018;378:1018-28.
Tenofovir didn’t prevent hepatitis B transmission to newborns
Prenatal tenofovir didn’t reduce the rate of hepatitis B among infants born to women infected with the virus.
Among 322 6-month-olds, the rate of HBV transmission was 0 in those whose mothers received the antiviral during pregnancy and 2% among those whose mothers received placebo – not a statistically significant difference, Gonzague Jourdain, MD, and his colleagues reported in the New England Journal of Medicine.
The study randomized 331 pregnant women with proven HBV infections to either tenofovir or placebo from 28 weeks’ gestation to 2 months post partum. All infants received HBV immune globulin at birth, and HBV vaccine at birth and at 1, 2, 4, and 6 months. The primary endpoint was confirmed HBV infection in the infant at 6 months.
Women were a mean of 28 weeks pregnant at baseline, with a mean viral load of 8.0 log10 IU/mL. Most women (about 90% of each group) had an HBV DNA of more than 200,000 IU/mL – a level associated with an increased risk of perinatal HBV infection despite vaccination.
There were 322 deliveries, resulting in 319 singletons, two pairs of twins, and one stillbirth. Postpartum infant treatment was quick, with a median of 1.3 hours from birth to administration of immune globulin and a median of 1.2 hours to administration of the first dose of the vaccine.
At 6 months, there were no HBV infections in the tenofovir-exposed group and 3 (2%) in the placebo group – a nonsignificant difference (P = .12).
Tenofovir was safe for both mother and fetus, with no significant adverse events in either group. The incidence of elevated maternal alanine aminotransferase level (more than 300 IU/L) was 6% in the tenofovir group and 3% in the placebo group, also a nonsignificant finding.
Dr. Jourdain and his colleagues noted that the 2% transmission rate in the placebo group is considerably lower than the 7% seen in similar studies and could be related to the rapid postpartum administration of HBV immune globulin and vaccine. If this is the case, prenatal antivirals could be more effective in countries where postpartum treatment is delayed or inconsistent.
“Maternal use of tenofovir may prevent transmissions that would occur when the birth dose is delayed, but its exact timing has not been reported consistently in previous perinatal studies,” the team said.
Another question is whether the stringent, 5-dose infant HBV vaccine series required in Thailand is simply more effective than schedules that have fewer doses or are combined with other vaccines and delivered later.
“It remains unclear whether the administration of more vaccine doses is more efficacious than the administration of the three vaccine doses that is recommended in the United States and by the World Health Organization.”
Dr. Jourdain had no financial disclosures relevant to the study, which was sponsored by the National Institute of Child Health and Human Development.
SOURCE: Jourdain G et al. N Engl J Med. 2018;378:911-23.
The trial by Jourdain et al. – although described by the authors as negative – “puts down an intriguing marker attesting to the possibility that rapidly phasing in the timely administration of a safe monovalent HBV vaccine within a few hours after birth could contribute to the interruption of mother-to-child transmission and avert preventable HBV infections in childhood,” Geoffrey Dusheiko, MD, wrote in an accompanying editorial (N Engl J Med. 2018;378:952-3).
The World Health Organization supports HBV vaccine schedules of three or four doses, which are usually given as part of a combination immunization protocol beginning at 6 weeks of age. “Currently, HBV vaccination is most frequently administered as a pentavalent or hexavalent vaccine as part of the Expanded Program on Immunization, typically in combination with vaccines against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type B,” wrote Dr. Dusheiko. “Paradoxically, support for combination vaccines within an integrated EPI schedule has unwittingly but undesirably shifted thinking and policy away from HBV vaccination at birth. This gap in vaccine strategy is disadvantageous.”
While the study doesn’t support tenofovir for maternal prophylaxis, it does imply value for treating the infant with immune globulin and HBV vaccination soon after birth. Delivering this kind of care globally will be challenging, but it’s entirely feasible, Dr. Dusheiko said.
“It is necessary to analyze regional data to assess the requirements for implementing vaccination at birth, including ... the training of otherwise unskilled birth attendants to deliver monovalent HBV vaccine at the same time as the vaccines against polio and bacille Calmette–Guérin. Importantly, the use of monovalent HBV vaccine would also require governmental or nongovernmental support. HBV vaccination at birth, despite the challenges for poverty-affected countries to deliver vaccination in rural and isolated locales, is feasible.”
Dr. Dusheiko is a hepatologist at the University College London School of Medicine and King’s College Hospital, London.
The trial by Jourdain et al. – although described by the authors as negative – “puts down an intriguing marker attesting to the possibility that rapidly phasing in the timely administration of a safe monovalent HBV vaccine within a few hours after birth could contribute to the interruption of mother-to-child transmission and avert preventable HBV infections in childhood,” Geoffrey Dusheiko, MD, wrote in an accompanying editorial (N Engl J Med. 2018;378:952-3).
The World Health Organization supports HBV vaccine schedules of three or four doses, which are usually given as part of a combination immunization protocol beginning at 6 weeks of age. “Currently, HBV vaccination is most frequently administered as a pentavalent or hexavalent vaccine as part of the Expanded Program on Immunization, typically in combination with vaccines against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type B,” wrote Dr. Dusheiko. “Paradoxically, support for combination vaccines within an integrated EPI schedule has unwittingly but undesirably shifted thinking and policy away from HBV vaccination at birth. This gap in vaccine strategy is disadvantageous.”
While the study doesn’t support tenofovir for maternal prophylaxis, it does imply value for treating the infant with immune globulin and HBV vaccination soon after birth. Delivering this kind of care globally will be challenging, but it’s entirely feasible, Dr. Dusheiko said.
“It is necessary to analyze regional data to assess the requirements for implementing vaccination at birth, including ... the training of otherwise unskilled birth attendants to deliver monovalent HBV vaccine at the same time as the vaccines against polio and bacille Calmette–Guérin. Importantly, the use of monovalent HBV vaccine would also require governmental or nongovernmental support. HBV vaccination at birth, despite the challenges for poverty-affected countries to deliver vaccination in rural and isolated locales, is feasible.”
Dr. Dusheiko is a hepatologist at the University College London School of Medicine and King’s College Hospital, London.
The trial by Jourdain et al. – although described by the authors as negative – “puts down an intriguing marker attesting to the possibility that rapidly phasing in the timely administration of a safe monovalent HBV vaccine within a few hours after birth could contribute to the interruption of mother-to-child transmission and avert preventable HBV infections in childhood,” Geoffrey Dusheiko, MD, wrote in an accompanying editorial (N Engl J Med. 2018;378:952-3).
The World Health Organization supports HBV vaccine schedules of three or four doses, which are usually given as part of a combination immunization protocol beginning at 6 weeks of age. “Currently, HBV vaccination is most frequently administered as a pentavalent or hexavalent vaccine as part of the Expanded Program on Immunization, typically in combination with vaccines against diphtheria, tetanus, pertussis, polio, and Haemophilus influenzae type B,” wrote Dr. Dusheiko. “Paradoxically, support for combination vaccines within an integrated EPI schedule has unwittingly but undesirably shifted thinking and policy away from HBV vaccination at birth. This gap in vaccine strategy is disadvantageous.”
While the study doesn’t support tenofovir for maternal prophylaxis, it does imply value for treating the infant with immune globulin and HBV vaccination soon after birth. Delivering this kind of care globally will be challenging, but it’s entirely feasible, Dr. Dusheiko said.
“It is necessary to analyze regional data to assess the requirements for implementing vaccination at birth, including ... the training of otherwise unskilled birth attendants to deliver monovalent HBV vaccine at the same time as the vaccines against polio and bacille Calmette–Guérin. Importantly, the use of monovalent HBV vaccine would also require governmental or nongovernmental support. HBV vaccination at birth, despite the challenges for poverty-affected countries to deliver vaccination in rural and isolated locales, is feasible.”
Dr. Dusheiko is a hepatologist at the University College London School of Medicine and King’s College Hospital, London.
Prenatal tenofovir didn’t reduce the rate of hepatitis B among infants born to women infected with the virus.
Among 322 6-month-olds, the rate of HBV transmission was 0 in those whose mothers received the antiviral during pregnancy and 2% among those whose mothers received placebo – not a statistically significant difference, Gonzague Jourdain, MD, and his colleagues reported in the New England Journal of Medicine.
The study randomized 331 pregnant women with proven HBV infections to either tenofovir or placebo from 28 weeks’ gestation to 2 months post partum. All infants received HBV immune globulin at birth, and HBV vaccine at birth and at 1, 2, 4, and 6 months. The primary endpoint was confirmed HBV infection in the infant at 6 months.
Women were a mean of 28 weeks pregnant at baseline, with a mean viral load of 8.0 log10 IU/mL. Most women (about 90% of each group) had an HBV DNA of more than 200,000 IU/mL – a level associated with an increased risk of perinatal HBV infection despite vaccination.
There were 322 deliveries, resulting in 319 singletons, two pairs of twins, and one stillbirth. Postpartum infant treatment was quick, with a median of 1.3 hours from birth to administration of immune globulin and a median of 1.2 hours to administration of the first dose of the vaccine.
At 6 months, there were no HBV infections in the tenofovir-exposed group and 3 (2%) in the placebo group – a nonsignificant difference (P = .12).
Tenofovir was safe for both mother and fetus, with no significant adverse events in either group. The incidence of elevated maternal alanine aminotransferase level (more than 300 IU/L) was 6% in the tenofovir group and 3% in the placebo group, also a nonsignificant finding.
Dr. Jourdain and his colleagues noted that the 2% transmission rate in the placebo group is considerably lower than the 7% seen in similar studies and could be related to the rapid postpartum administration of HBV immune globulin and vaccine. If this is the case, prenatal antivirals could be more effective in countries where postpartum treatment is delayed or inconsistent.
“Maternal use of tenofovir may prevent transmissions that would occur when the birth dose is delayed, but its exact timing has not been reported consistently in previous perinatal studies,” the team said.
Another question is whether the stringent, 5-dose infant HBV vaccine series required in Thailand is simply more effective than schedules that have fewer doses or are combined with other vaccines and delivered later.
“It remains unclear whether the administration of more vaccine doses is more efficacious than the administration of the three vaccine doses that is recommended in the United States and by the World Health Organization.”
Dr. Jourdain had no financial disclosures relevant to the study, which was sponsored by the National Institute of Child Health and Human Development.
SOURCE: Jourdain G et al. N Engl J Med. 2018;378:911-23.
Prenatal tenofovir didn’t reduce the rate of hepatitis B among infants born to women infected with the virus.
Among 322 6-month-olds, the rate of HBV transmission was 0 in those whose mothers received the antiviral during pregnancy and 2% among those whose mothers received placebo – not a statistically significant difference, Gonzague Jourdain, MD, and his colleagues reported in the New England Journal of Medicine.
The study randomized 331 pregnant women with proven HBV infections to either tenofovir or placebo from 28 weeks’ gestation to 2 months post partum. All infants received HBV immune globulin at birth, and HBV vaccine at birth and at 1, 2, 4, and 6 months. The primary endpoint was confirmed HBV infection in the infant at 6 months.
Women were a mean of 28 weeks pregnant at baseline, with a mean viral load of 8.0 log10 IU/mL. Most women (about 90% of each group) had an HBV DNA of more than 200,000 IU/mL – a level associated with an increased risk of perinatal HBV infection despite vaccination.
There were 322 deliveries, resulting in 319 singletons, two pairs of twins, and one stillbirth. Postpartum infant treatment was quick, with a median of 1.3 hours from birth to administration of immune globulin and a median of 1.2 hours to administration of the first dose of the vaccine.
At 6 months, there were no HBV infections in the tenofovir-exposed group and 3 (2%) in the placebo group – a nonsignificant difference (P = .12).
Tenofovir was safe for both mother and fetus, with no significant adverse events in either group. The incidence of elevated maternal alanine aminotransferase level (more than 300 IU/L) was 6% in the tenofovir group and 3% in the placebo group, also a nonsignificant finding.
Dr. Jourdain and his colleagues noted that the 2% transmission rate in the placebo group is considerably lower than the 7% seen in similar studies and could be related to the rapid postpartum administration of HBV immune globulin and vaccine. If this is the case, prenatal antivirals could be more effective in countries where postpartum treatment is delayed or inconsistent.
“Maternal use of tenofovir may prevent transmissions that would occur when the birth dose is delayed, but its exact timing has not been reported consistently in previous perinatal studies,” the team said.
Another question is whether the stringent, 5-dose infant HBV vaccine series required in Thailand is simply more effective than schedules that have fewer doses or are combined with other vaccines and delivered later.
“It remains unclear whether the administration of more vaccine doses is more efficacious than the administration of the three vaccine doses that is recommended in the United States and by the World Health Organization.”
Dr. Jourdain had no financial disclosures relevant to the study, which was sponsored by the National Institute of Child Health and Human Development.
SOURCE: Jourdain G et al. N Engl J Med. 2018;378:911-23.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Key clinical point: Tenofovir was no different than placebo in preventing HBV transmission to newborns.
Major finding: The transmission rate was 0% in the tenofovir group and 2% in the placebo group (P = .12).
Study details: The study randomized 331 pregnant women to tenofovir or placebo from gestational week 28 to 2 months postpartum.
Disclosures: Dr. Jourdain had no financial disclosures; the National Institute of Child Health and Development sponsored the study.
Source: Jourdain G et al. N Engl J Med. 2018;378:911-23.
Treat to target in RA: Finding the right path forward
It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.
That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.
So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.
But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.
“There are patient reasons. There are doctor reasons. And there are extrinsic reasons. But I would say the number one reason it’s had limited adoption is that it simply hasn’t been made easy enough.”
The ABCs of TTT
In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.
Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.
Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.
It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA1c [hemoglobin A1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”
Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.
The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.
Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.
Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.
But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.
Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.
In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).
The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.
Slow on the uptake
Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.
Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.
Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.
“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”
The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”
He and his colleagues investigated whether a 9-month group-based learning collaborative could improve TTT numbers among 46 rheumatologists at 11 practices. The endpoint was a combination of four TTT principles: recording a disease target, recording a disease activity measure, engaging in shared decision-making, and changing treatment if disease target hasn’t been reached.
At baseline, 64% of visits to these rheumatologists had none of the TTT components present, 33% had one component, and 2.3% had two components; just 3% of the visits included all of the components (Arthritis Care Res. 2017 Aug 22. doi: 10.1002/acr.23343).
The project consisted of nine sessions, most conducted by webinar. The entire practice team took part, learning the principles and practices of TTT, identifying their unique barriers to implementing it, and coming up with their unique way of integrating TTT into their practice. It was fairly successful, Dr. Solomon said in an interview. After the intervention, 57% of the exposed practices had incorporated TTT.
In January, Dr. Solomon published a follow-up study of the stability of those changes (Arthritis Care Res. 2018 Jan 5. doi: 10.1002/acr.23508). He was impressed with the results. Most sites from the first cohort had sustained the improvement during the second training period (52%).
“We found that people could implement it effectively when we gave them the tools to do it,” he said. “It’s definitely achievable, but it takes some commitment and guidance, and the realization that everyone can contribute to success in a collaborative manner.”
Technology, or the lack of it
Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.
But at the same time, he freely admits that the time spent ticking boxes on a paper form or a computer, and being forced to report those to a federal agency, could be the camel-breaking straw for many.
“It’s going down the path of what makes medicine sucky,” he said in an interview. “Bean counters telling me how to practice medicine, who think they can use this TTT to manage what I do. I don’t need more people trying to regulate my life.”
Dr. Cush has conducted surveys on physician burnout and depression. “Administrative tasks and electronic records are a large part why 24% of people are burning out in medicine.”
Right now, there’s no easy way for many rheumatologists to incorporate regular DAM measures into their EHR system. The extra steps needed to get them there impede physician compliance with the strategy, he and Dr. Curtis agreed. But, Dr. Curtis said, there’s an app for that.
He is the developer of the Rheumatic Disease Activity (READY) measure. The iPad/iPhone app, which is free to download in the app store, is an electronic measurement tool that efficiently captures patient-reported outcomes in RA and other rheumatic conditions.
“This tool really makes it much easier to collect DAM from patients,” Dr. Curtis said. “It is designed for the doc who says, ‘I would take data from patients, just make it easy for me to do that.’ It takes 5-10 minutes to complete, and you get information about pain, fatigue, anxiety, and social interactions and, he said, can be easily integrated into work flow.
On a practice-provided device, the patient answers questions validated on the National Institutes of Health Patient-Reported Outcomes Measurement Information System. It includes a number of electronically scored and validated DAMs and provides trend charts to visualize longitudinal score data and track patient health status over multiple encounters. There are also places to record data about current and past medications.
“The docs input no data, which is the usual deal-killer. All they have to do is figure out how to integrate it into the work flow.”
“ACR has been communicating with the major EMR providers out there to make this easier. We are seeing some tools for iPads and smartphones, as well as paper tools.”
The ACR RISE Registry is another option, said Evan Leibowitz, MD, a rheumatologist in Midland Park, N.J.
“RISE is open to all rheumatologists in this country, and ACR has tried to make it as easy as possible. It can interface with most EMRs. All the physician does is collect the data, and it gets transferred to a HIPAA-protected database where it’s analyzed and presented back to the doctors so they can look at all their metrics. It’s currently the least painful way to get involved in a registry, I think.”
But just as techies are rolling out ways to interface DAMs and EHRs, medicine is marching forward. A new blood test called VECTRA DA measures 12 inflammatory biomarkers and may provide all the information needed to make treatment escalation decisions, Dr. Leibowitz said.
“The least painful option will probably be the VECTRA DA score. It’s a single blood test, which we can do easily since we already draw blood. Rather than filling out a RAPID3 [Routine Assessment of Patient Index Data 3] or a CDAI [Clinical Disease Activity Index], we draw the blood, send it to the company, [and] they return us a score that indicates low, moderate, or high disease activity.”
Studies have found that not only is the VECTRA DA score a good clinical management tool, predicting responses, it can also predict impending relapse.
TTT challenges patients, too
Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.
“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”
Researchers have explored these questions.
Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).
“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”
The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”
Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”
“As a physician, I’m worried about the rare and extremely rare adverse events – things that are really dreaded, that can be fatal. However, these happen in only a couple out of tens of thousands of patients. On the other hand, there are common side effects that occur in up to 20% of our patients. They’re not a serious threat to health, but they impact quality of life every day with nausea, dizziness, diarrhea, headache, and brain fog. As rheumatologists, we really undervalue these, and guess what? When we ask patients, it turns out that nausea and dizziness and diarrhea are not things that they want in their daily lives.”
Dr. Fraenkel of Yale University, New Haven, Conn., explored this topic in a recently published survey of 1,273 RA patients that sought their concerns about taking triple therapy, biologics, and Janus kinase inhibitors (Ann Rheum Dis. 2017 Dec 15. doi: 10.1136/annrheumdis-2017-212407). The survey included seven medication attributes – administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information, and cost – and sought to determine the relative effect of each attribute on patient preference for different treatment options.
“We found five distinct clusters” of patients, Dr. Fraenkel said in an interview. “I will admit I was surprised when I saw the largest group (38%) was most concerned about the cost of their medications. Our assumption is always that the rare and dreaded side effects are the most concerning, but for these patients, cost was the dominant issue. It’s the No. 1 reason patients are noncompliant with their initial treatment recommendations. And with the cost of our biologics, it is a very big deal.”
Her reaction pinpoints an important obstacle in shared decision making: physician bias. “I’d say the vast majority of us argue that the benefit of TTT outweighs the harms. We minimize inflammation, so patients will live longer with less disease impact. But how we get there should be up to the patient. My biases shouldn’t come into play. The decision to intensify is different than the decision about how to intensify. This is where the back-and-forth comes in, making sure the patient understands the pros and cons of escalating or not. If she decided no, she doesn’t incur the risk of a new medication, but she does incur the risk of progressing. The bottom line is that physicians should not bring their biases to the table but describe the facts, the importance of which will be different to different patients who have different goals.”
A patient’s story: Overcoming fear and self-image
Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.
As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.
But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.
“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”
“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.
The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.
Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.
“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”
She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.
“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”
As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”
With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.
“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”
Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.
Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.
“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”
She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.
“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”
The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”
Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.
“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”
It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.
That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.
So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.
But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.
“There are patient reasons. There are doctor reasons. And there are extrinsic reasons. But I would say the number one reason it’s had limited adoption is that it simply hasn’t been made easy enough.”
The ABCs of TTT
In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.
Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.
Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.
It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA1c [hemoglobin A1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”
Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.
The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.
Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.
Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.
But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.
Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.
In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).
The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.
Slow on the uptake
Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.
Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.
Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.
“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”
The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”
He and his colleagues investigated whether a 9-month group-based learning collaborative could improve TTT numbers among 46 rheumatologists at 11 practices. The endpoint was a combination of four TTT principles: recording a disease target, recording a disease activity measure, engaging in shared decision-making, and changing treatment if disease target hasn’t been reached.
At baseline, 64% of visits to these rheumatologists had none of the TTT components present, 33% had one component, and 2.3% had two components; just 3% of the visits included all of the components (Arthritis Care Res. 2017 Aug 22. doi: 10.1002/acr.23343).
The project consisted of nine sessions, most conducted by webinar. The entire practice team took part, learning the principles and practices of TTT, identifying their unique barriers to implementing it, and coming up with their unique way of integrating TTT into their practice. It was fairly successful, Dr. Solomon said in an interview. After the intervention, 57% of the exposed practices had incorporated TTT.
In January, Dr. Solomon published a follow-up study of the stability of those changes (Arthritis Care Res. 2018 Jan 5. doi: 10.1002/acr.23508). He was impressed with the results. Most sites from the first cohort had sustained the improvement during the second training period (52%).
“We found that people could implement it effectively when we gave them the tools to do it,” he said. “It’s definitely achievable, but it takes some commitment and guidance, and the realization that everyone can contribute to success in a collaborative manner.”
Technology, or the lack of it
Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.
But at the same time, he freely admits that the time spent ticking boxes on a paper form or a computer, and being forced to report those to a federal agency, could be the camel-breaking straw for many.
“It’s going down the path of what makes medicine sucky,” he said in an interview. “Bean counters telling me how to practice medicine, who think they can use this TTT to manage what I do. I don’t need more people trying to regulate my life.”
Dr. Cush has conducted surveys on physician burnout and depression. “Administrative tasks and electronic records are a large part why 24% of people are burning out in medicine.”
Right now, there’s no easy way for many rheumatologists to incorporate regular DAM measures into their EHR system. The extra steps needed to get them there impede physician compliance with the strategy, he and Dr. Curtis agreed. But, Dr. Curtis said, there’s an app for that.
He is the developer of the Rheumatic Disease Activity (READY) measure. The iPad/iPhone app, which is free to download in the app store, is an electronic measurement tool that efficiently captures patient-reported outcomes in RA and other rheumatic conditions.
“This tool really makes it much easier to collect DAM from patients,” Dr. Curtis said. “It is designed for the doc who says, ‘I would take data from patients, just make it easy for me to do that.’ It takes 5-10 minutes to complete, and you get information about pain, fatigue, anxiety, and social interactions and, he said, can be easily integrated into work flow.
On a practice-provided device, the patient answers questions validated on the National Institutes of Health Patient-Reported Outcomes Measurement Information System. It includes a number of electronically scored and validated DAMs and provides trend charts to visualize longitudinal score data and track patient health status over multiple encounters. There are also places to record data about current and past medications.
“The docs input no data, which is the usual deal-killer. All they have to do is figure out how to integrate it into the work flow.”
“ACR has been communicating with the major EMR providers out there to make this easier. We are seeing some tools for iPads and smartphones, as well as paper tools.”
The ACR RISE Registry is another option, said Evan Leibowitz, MD, a rheumatologist in Midland Park, N.J.
“RISE is open to all rheumatologists in this country, and ACR has tried to make it as easy as possible. It can interface with most EMRs. All the physician does is collect the data, and it gets transferred to a HIPAA-protected database where it’s analyzed and presented back to the doctors so they can look at all their metrics. It’s currently the least painful way to get involved in a registry, I think.”
But just as techies are rolling out ways to interface DAMs and EHRs, medicine is marching forward. A new blood test called VECTRA DA measures 12 inflammatory biomarkers and may provide all the information needed to make treatment escalation decisions, Dr. Leibowitz said.
“The least painful option will probably be the VECTRA DA score. It’s a single blood test, which we can do easily since we already draw blood. Rather than filling out a RAPID3 [Routine Assessment of Patient Index Data 3] or a CDAI [Clinical Disease Activity Index], we draw the blood, send it to the company, [and] they return us a score that indicates low, moderate, or high disease activity.”
Studies have found that not only is the VECTRA DA score a good clinical management tool, predicting responses, it can also predict impending relapse.
TTT challenges patients, too
Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.
“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”
Researchers have explored these questions.
Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).
“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”
The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”
Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”
“As a physician, I’m worried about the rare and extremely rare adverse events – things that are really dreaded, that can be fatal. However, these happen in only a couple out of tens of thousands of patients. On the other hand, there are common side effects that occur in up to 20% of our patients. They’re not a serious threat to health, but they impact quality of life every day with nausea, dizziness, diarrhea, headache, and brain fog. As rheumatologists, we really undervalue these, and guess what? When we ask patients, it turns out that nausea and dizziness and diarrhea are not things that they want in their daily lives.”
Dr. Fraenkel of Yale University, New Haven, Conn., explored this topic in a recently published survey of 1,273 RA patients that sought their concerns about taking triple therapy, biologics, and Janus kinase inhibitors (Ann Rheum Dis. 2017 Dec 15. doi: 10.1136/annrheumdis-2017-212407). The survey included seven medication attributes – administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information, and cost – and sought to determine the relative effect of each attribute on patient preference for different treatment options.
“We found five distinct clusters” of patients, Dr. Fraenkel said in an interview. “I will admit I was surprised when I saw the largest group (38%) was most concerned about the cost of their medications. Our assumption is always that the rare and dreaded side effects are the most concerning, but for these patients, cost was the dominant issue. It’s the No. 1 reason patients are noncompliant with their initial treatment recommendations. And with the cost of our biologics, it is a very big deal.”
Her reaction pinpoints an important obstacle in shared decision making: physician bias. “I’d say the vast majority of us argue that the benefit of TTT outweighs the harms. We minimize inflammation, so patients will live longer with less disease impact. But how we get there should be up to the patient. My biases shouldn’t come into play. The decision to intensify is different than the decision about how to intensify. This is where the back-and-forth comes in, making sure the patient understands the pros and cons of escalating or not. If she decided no, she doesn’t incur the risk of a new medication, but she does incur the risk of progressing. The bottom line is that physicians should not bring their biases to the table but describe the facts, the importance of which will be different to different patients who have different goals.”
A patient’s story: Overcoming fear and self-image
Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.
As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.
But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.
“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”
“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.
The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.
Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.
“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”
She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.
“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”
As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”
With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.
“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”
Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.
Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.
“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”
She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.
“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”
The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”
Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.
“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”
It makes intuitive sense: Setting a specific goal and working quickly and systematically toward it should bring better results than slowly floundering toward an amorphous endpoint.
That’s the basic idea behind treat-to-target (TTT) strategies in rheumatoid arthritis, and since 2010, data seem to support it: Rheumatologists who pick a therapeutic goal and a related disease activity measure and work in partnership with cooperative patients to achieve it, get better clinical responses.
So important has this concept become that it’s now being tied to reimbursement. Rheumatologists who submit proof that they record disease activity measures in their patients will get points toward fulfilling quality reporting requirements for the Merit-Based Incentive Payment System (MIPS) option in the Quality Payment Program established by the Medicare Access and CHIP Reauthorization Act of 2015. Those points go toward achieving a bonus in Medicare reimbursement; those who can’t show it will edge toward a financial ding.
But despite the twin carrots of better patient outcomes and bonus payments from the Centers for Medicare & Medicaid Services and the stick of a 4%-9% Medicare payment penalty during the years 2019-2022 (and 9% thereafter) for quality outcome measures reported in 2017 and beyond, studies show that up to 60% of U.S. rheumatologists don’t regularly incorporate TTT strategies into how they treat their RA patients.
“There are patient reasons. There are doctor reasons. And there are extrinsic reasons. But I would say the number one reason it’s had limited adoption is that it simply hasn’t been made easy enough.”
The ABCs of TTT
In 2010, Austrian rheumatologist Josef Smolen, MD, leading an international task force, proposed 10 recommendations for improving the care of patients with RA. These were based on the concept that choosing a therapeutic target – low disease activity or remission – and aggressively pursuing it with frequent medication changes accompanied by frequent disease activity measurements would result in improved short- and long-term outcomes.
Disease activity measures (DAMs) were crucial to the concept. In order to treat to a target, one must not only choose a target but also have a validated means to regularly measure progress. The task force didn’t say which DAM would be most appropriate, and research since then suggests that the tool used to measure progress doesn’t matter nearly as much as the target itself.
Shared decision making is also a core tenet of the technique. Physicians work with patients to identify the best treatment target for each individual and decide together how to reach it.
It is not a new concept, Dr. Smolen and his colleagues explained in their landmark paper (Ann Rheum Dis. 2010 Apr;69[4]:631-7). “In many other areas of medicine, treatment targets have been defined to improve outcomes, leading to a reduction in the risk of organ damage. In the care of patients with diabetes, hyperlipidemia, and hypertension, these aspects have been adopted widely in practice; doctors order laboratory tests for cholesterol and triglycerides, blood glucose and HbA1c [hemoglobin A1c] levels, check blood pressure, and adapt therapy accordingly, and patients know these values and are aware of the treatment targets.”
Yet rheumatologists had not adopted a similar paradigm, despite the surge in availability of effective disease-modifying antirheumatic drugs (DMARDs). Although clinical studies of these new drugs clearly showed that remission was possible for many patients and that achieving remission quickly could prevent irreversible joint damage, few patients were getting those drugs even if they had long-standing disease.
The task force suggested setting a treatment aim of remission or low disease activity, seeing patients every 1-3 months, and switching therapy as often as necessary to reach that goal. Tracking improvement required consistent measurements and recording of a DAM. The recommendations, which were updated in 2014, didn’t specify a certain DAM, saying that the patient’s individual clinical picture should guide that choice (Ann Rheum Dis. 2016 Jan;75[1]:3-15). Shared decision making between the patient and rheumatologist was at the foundation of this concept.
Fast-forward to 2015. As TTT was increasingly embraced in Europe, data began to emerge supporting its clinical validity. A study presented at the American College of Rheumatology (ACR) annual meeting in San Francisco that year showed that treating RA patients toward a target of remission or low disease activity worked immediately and resulted in higher remission rates.
Sofia Ramiro, MD, of Leiden (Netherlands) University Medical Center found that employing a TTT strategy increased the likelihood that a patient would achieve remission by 52%. She also found that TTT strategies lowered disease activity and even improved remission rates for patients who had never received DMARDs.
But in 2017, a meta-analysis found conflicting results among the 16 published randomized, controlled trials comparing TTT against usual care (Health Technol Assess 2017. doi: 10.3310/hta21710). The authors concluded that TTT was more effective for newly diagnosed patients, in whom it increased the chance of remission by about 50%. For those with longstanding disease, TTT was not significantly different from usual care.
Despite limited, and somewhat contradictory, clinical evidence, TTT is becoming increasingly accepted, especially in Europe. In 2016, the European League Against Rheumatism updated its recommendations for RA management (Ann Rheum Dis. 2017 Jun;76[6]:960-77). The document contained a recommendation to use low disease activity or sustained remission as the treatment target for every patient, to monitor disease activity with a validated measure every 1-3 months, and to change therapy as often as every 3 months in the case of no improvement or by 6 months if the target hasn’t been reached.
In its most recent 2015 RA treatment guidelines, the ACR also endorsed the strategy, though somewhat obliquely, and did not require rheumatologists to conform to it (Arthritis Care Res. 2016 Jan;68[1]:1-25).
The concept of TTT, if not the explicit demand to practice it, now appears in the list of quality indicators rheumatologists can choose from in order to fulfill quality performance reporting requirements in Merit-Based Incentive Payment System. Periodic assessment of disease activity in RA patients with a validated DAM is one of the acceptable quality measures for rheumatology. It’s not designated as a high-priority measure, but there it is, item No. 177, tying clinicians at least indirectly to a TTT approach for their Medicare patients: The percentage of patients aged 18 years and older with a diagnosis of RA who have an assessment and classification of disease activity within 12 months.
Slow on the uptake
Despite the data and the dictum, however, TTT remains an outlier in the United States. The most recent studies suggest that most U.S. rheumatologists do not employ it.
Dr. Curtis is the primary author on one of the newest studies, which employed a 26-question survey about the use of a quantitative measurement in RA patients and attitudes about using it (J Rheumatol. 2018 Jan;45[1]:40-4). The survey went out to almost 2,000 rheumatologists; 439 returned it.
Overall, just 44% said they “always practice in a treat-to-target manner, regularly using a scoring metric.” Younger physicians, those in group practices, and those who made regular use of TNF inhibitors were more likely to practice this way. A total of 35% said they never used a quantitative metric for their RA patients.
“The No. 1 reason given about not using them is that it’s too time-consuming and not easy enough,” Dr. Curtis said in an interview. “Logistics is a key barrier.” Busy clinicians don’t want to spend time entering data into an electronic medical record, and there aren’t easy ways to merge a specific DAM with a practice’s chosen EHR. “There’s a hassle factor, for sure.”
The age gap was interesting but not unexpected, he said. “Older rheumatologists say they like to go by their gut, by a clinical gestalt,” Dr. Curtis said, while younger physicians without decades of experience are more comfortable with such clinical tools. For some, age contributes to a kind of clinical inertia. “Doctors trained in an earlier era might be more tolerant of patients not doing as well. I’m a younger physician, and I have never known the era of not having biologics. They lived and practiced in that era, so their spectrum of what’s ‘normal’ and acceptable for patient progress may be wider.”
He and his colleagues investigated whether a 9-month group-based learning collaborative could improve TTT numbers among 46 rheumatologists at 11 practices. The endpoint was a combination of four TTT principles: recording a disease target, recording a disease activity measure, engaging in shared decision-making, and changing treatment if disease target hasn’t been reached.
At baseline, 64% of visits to these rheumatologists had none of the TTT components present, 33% had one component, and 2.3% had two components; just 3% of the visits included all of the components (Arthritis Care Res. 2017 Aug 22. doi: 10.1002/acr.23343).
The project consisted of nine sessions, most conducted by webinar. The entire practice team took part, learning the principles and practices of TTT, identifying their unique barriers to implementing it, and coming up with their unique way of integrating TTT into their practice. It was fairly successful, Dr. Solomon said in an interview. After the intervention, 57% of the exposed practices had incorporated TTT.
In January, Dr. Solomon published a follow-up study of the stability of those changes (Arthritis Care Res. 2018 Jan 5. doi: 10.1002/acr.23508). He was impressed with the results. Most sites from the first cohort had sustained the improvement during the second training period (52%).
“We found that people could implement it effectively when we gave them the tools to do it,” he said. “It’s definitely achievable, but it takes some commitment and guidance, and the realization that everyone can contribute to success in a collaborative manner.”
Technology, or the lack of it
Many rheumatologists view TTT and the consistent measuring it involves as just one more headache-inducing time suck, said John Cush, MD.
But at the same time, he freely admits that the time spent ticking boxes on a paper form or a computer, and being forced to report those to a federal agency, could be the camel-breaking straw for many.
“It’s going down the path of what makes medicine sucky,” he said in an interview. “Bean counters telling me how to practice medicine, who think they can use this TTT to manage what I do. I don’t need more people trying to regulate my life.”
Dr. Cush has conducted surveys on physician burnout and depression. “Administrative tasks and electronic records are a large part why 24% of people are burning out in medicine.”
Right now, there’s no easy way for many rheumatologists to incorporate regular DAM measures into their EHR system. The extra steps needed to get them there impede physician compliance with the strategy, he and Dr. Curtis agreed. But, Dr. Curtis said, there’s an app for that.
He is the developer of the Rheumatic Disease Activity (READY) measure. The iPad/iPhone app, which is free to download in the app store, is an electronic measurement tool that efficiently captures patient-reported outcomes in RA and other rheumatic conditions.
“This tool really makes it much easier to collect DAM from patients,” Dr. Curtis said. “It is designed for the doc who says, ‘I would take data from patients, just make it easy for me to do that.’ It takes 5-10 minutes to complete, and you get information about pain, fatigue, anxiety, and social interactions and, he said, can be easily integrated into work flow.
On a practice-provided device, the patient answers questions validated on the National Institutes of Health Patient-Reported Outcomes Measurement Information System. It includes a number of electronically scored and validated DAMs and provides trend charts to visualize longitudinal score data and track patient health status over multiple encounters. There are also places to record data about current and past medications.
“The docs input no data, which is the usual deal-killer. All they have to do is figure out how to integrate it into the work flow.”
“ACR has been communicating with the major EMR providers out there to make this easier. We are seeing some tools for iPads and smartphones, as well as paper tools.”
The ACR RISE Registry is another option, said Evan Leibowitz, MD, a rheumatologist in Midland Park, N.J.
“RISE is open to all rheumatologists in this country, and ACR has tried to make it as easy as possible. It can interface with most EMRs. All the physician does is collect the data, and it gets transferred to a HIPAA-protected database where it’s analyzed and presented back to the doctors so they can look at all their metrics. It’s currently the least painful way to get involved in a registry, I think.”
But just as techies are rolling out ways to interface DAMs and EHRs, medicine is marching forward. A new blood test called VECTRA DA measures 12 inflammatory biomarkers and may provide all the information needed to make treatment escalation decisions, Dr. Leibowitz said.
“The least painful option will probably be the VECTRA DA score. It’s a single blood test, which we can do easily since we already draw blood. Rather than filling out a RAPID3 [Routine Assessment of Patient Index Data 3] or a CDAI [Clinical Disease Activity Index], we draw the blood, send it to the company, [and] they return us a score that indicates low, moderate, or high disease activity.”
Studies have found that not only is the VECTRA DA score a good clinical management tool, predicting responses, it can also predict impending relapse.
TTT challenges patients, too
Rheumatologists are not the only ones reluctant to embrace TTT. It challenges patients as well, in a number of ways.
“Patients have to be willing to change treatments as often as you need them to, and that can be every 3-6 months, or even more quickly,” Dr. Curtis said. “The cost can be a factor. And a lot of patients are risk averse. They feel there may be more of a downside to switching than a benefit to be gained, especially if they’ve had RA for a while. Maybe they’re feeling a lot better than they were; their disease is still active, but they don’t feel bad enough to want to change medications.”
Researchers have explored these questions.
Last year, Dr. Michaud published a survey of 48 RA patients who were interviewed about their experiences with DMARDs and the feelings that would prompt them to comply with a treatment regimen – or resist one (Arthritis Care Res. 2017 June 2. doi: 10.1002/acr.23301).
“For patients’ motivations to accept treatment regimens, two themes emerged,” said Dr. Michaud, who is also codirector of the National Data Bank for Rheumatic Diseases. “One, the desire to return to a ‘normal’ life and, two, the fear of future disability due to RA. For motivations to resist treatment regimens, five themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.”
The findings confirm one of TTT’s core tenets: involving patients in treatment decisions, Dr. Michaud said in an interview. “A lot of patients in my studies have reached a place of ‘OK-ness’ with their RA. The don’t want to change what they feel is working. They’re afraid of getting worse because they’ve been there and know what that can be.”
Rapid change-ups to new medications are especially intimidating to long-term patients, he said. “This is a very important aspect of resistance to change. The side effects of these medications, both major and minor, are not something that people want to experience.”
“As a physician, I’m worried about the rare and extremely rare adverse events – things that are really dreaded, that can be fatal. However, these happen in only a couple out of tens of thousands of patients. On the other hand, there are common side effects that occur in up to 20% of our patients. They’re not a serious threat to health, but they impact quality of life every day with nausea, dizziness, diarrhea, headache, and brain fog. As rheumatologists, we really undervalue these, and guess what? When we ask patients, it turns out that nausea and dizziness and diarrhea are not things that they want in their daily lives.”
Dr. Fraenkel of Yale University, New Haven, Conn., explored this topic in a recently published survey of 1,273 RA patients that sought their concerns about taking triple therapy, biologics, and Janus kinase inhibitors (Ann Rheum Dis. 2017 Dec 15. doi: 10.1136/annrheumdis-2017-212407). The survey included seven medication attributes – administration, onset, bothersome side effects, serious infection, very rare side effects, amount of information, and cost – and sought to determine the relative effect of each attribute on patient preference for different treatment options.
“We found five distinct clusters” of patients, Dr. Fraenkel said in an interview. “I will admit I was surprised when I saw the largest group (38%) was most concerned about the cost of their medications. Our assumption is always that the rare and dreaded side effects are the most concerning, but for these patients, cost was the dominant issue. It’s the No. 1 reason patients are noncompliant with their initial treatment recommendations. And with the cost of our biologics, it is a very big deal.”
Her reaction pinpoints an important obstacle in shared decision making: physician bias. “I’d say the vast majority of us argue that the benefit of TTT outweighs the harms. We minimize inflammation, so patients will live longer with less disease impact. But how we get there should be up to the patient. My biases shouldn’t come into play. The decision to intensify is different than the decision about how to intensify. This is where the back-and-forth comes in, making sure the patient understands the pros and cons of escalating or not. If she decided no, she doesn’t incur the risk of a new medication, but she does incur the risk of progressing. The bottom line is that physicians should not bring their biases to the table but describe the facts, the importance of which will be different to different patients who have different goals.”
A patient’s story: Overcoming fear and self-image
Prisha Acharya, PhD, knows a thing or two about rheumatoid arthritis.
As an RA researcher in New York, Dr. Acharya has a vast store of knowledge at her fingertips – everything from long-term treatment outcomes to medication side effects.
But when she was diagnosed with RA last year, at age 38 years, she was overwhelmed. And when she connected with a rheumatologist who wanted to aggressively treat her to a target of low disease activity or even remission, she balked. She became the patient who refuses a treat-to-target strategy.
“He was very clear in communicating the urgency of needing to get the disease under control, and I agreed that was a good thing. But even with all this experience in research, I still felt this resistance. I knew I needed to go aggressive. But I was also worried – worried about the side effects, the long-term effects, the costs. Committing to it was going to make my diagnosis real. I wasn’t ready to do it.”
“Prisha Acharya” is not this patient’s real name. She spoke in an interview on the condition of anonymity because she hasn’t yet discussed her diagnosis with some of her family and friends. In fact, she’s still coming to grips with it herself.
The story of Dr. Acharya’s journey to an RA clinic is one she hears every day in her work. About a year ago, she had some aching and stiffness in her knee, and it spread to her wrists and fingers. Digestive issues arose. She shuffled from doctor to doctor, had knee surgery, visited a gastroenterologist, went on a fibromyalgia medication. She finally broached the topic of a possible autoimmune disorder. By the time she received an RA diagnosis, she could only think of one thing: feeling better.
Her rheumatologist got that. But he also let her know at the first visit that he wanted more for her.
“He said, ‘We’re going to get you feeling better, reduce your pain, and make it so you can get out of bed in the morning,’ but our very first conversation was also about a goal of low disease activity and remission. He explained that we had a brief window of opportunity to make a difference in preventing long-term joint damage and that we had to go for it.”
She was on board with the goal, intellectually at least. However, her gut said something different, especially when they discussed methotrexate.
“There was an association in my head between methotrexate and chemotherapy. I knew it could cause fatigue, nausea, and hair thinning. And the idea of an injection, like I was getting chemo for cancer ... it felt very scary.”
As a compromise, she started hydroxychloroquine and shortly after, added sulfasalazine. She was feeling better, but her disease activity scores were still elevated. “My inflammation scores were climbing, and all this time he was saying ‘You have to start methotrexate. You’re going against my advice,’ but I was not emotionally ready. Despite my experience with RA research, I wouldn’t start it.”
With every visit, her rheumatologist patiently built his case for treatment. With every visit, her relationship and trust of him grew.
“Finally, just recently, I did start methotrexate, first with the pill and now the self-injector. I’m on that and the sulfasalazine, but we are reassessing again soon because I still have pain and my disease still isn’t under control. Now we’re going to talk about increasing the methotrexate and adding a new therapy.”
Dr. Acharya’s experience points to the dichotomy between what patients and physicians see as the most important goals and provides a good lesson about how trust and communication can bring those into clinical alignment.
Her rheumatologist set a very clear goal at the beginning of her treatment – one that came with a price tag she wasn’t yet willing to pay. But he also heard and accepted her goal: She wanted to feel better and give herself time to adjust to a new way of life and a new understanding of who she was.
“His language really helped,” Dr. Archaya said. “He acknowledged what I needed – to get the pain and stiffness under control. And as we built our relationship, I was able to hear his side about the urgency of treatment much better. When I was willing to go aggressive, I was also willing to say ‘I have RA.’ It takes a while to get there.”
She had some words of advice to help rheumatologists bridge the gap between what they want for a patient and what that patient wants for herself.
“An open dialogue is really going to help. When patients are voicing their fears, the rheumatologist can reassure them that, if this medicine doesn’t help or if it gives you terrible side effects, we can work together to find another option. Also, it’s so important for the patient to understand the treat-to-target framework from the very beginning. Everything indicates that the earlier we start treatment and set a goal, the better we can control our disease and the better the rest of our life can be.”
The second thing, Dr. Acharya said, is shared decision making. “I want him to tell me the options but also to work with me at arriving at the decision I eventually make.”
Finally, she said, patients need other resources, and rheumatologists can help direct them to find those.
“It’s so important to connect with like-minded patients in patient advocacy groups. The tips that they have given me about medications and dealing with my disease, no doctor could ever give me because patients are the ones that know those things inside-out.”
Here are the ‘must-see’ sessions at HM18
Welcome to Hospital Medicine 2018, the second-happiest place in Orlando – at least for hospitalists who want to be in the know.
The 2018 education program is a ride through the diverse world of hospital medicine, with sessions ranging from clinical updates to cutting-edge techniques, communication tools, building a satisfying career, and finding your way through tangles of red tape and policy.
Two tracks new for 2018 hone in on managing alternative providers and palliative care.
The half-day NP/PA track (beginning April 11 at 7:30 a.m.) recognizes these practitioners for their crucial roles in hospital medicine care delivery. Among the discussions aimed at hospitalists: Best practices in provider utilization and collaboration; supervision vs. collaboration; and challenging situations when working with mid-level providers.
The palliative care track (also a half day, starting April 11 at 10 a.m.) recognizes the crucial role hospitalists play in optimizing end-of-life care. Sessions will help hospitalists understand that role, and guide them in managing pain and other symptoms commonly encountered during this transitional time.
As for the rest of the meeting, picking favorites is as tough as picking between Disney’s Big Thunder Railroad and Splash Mountain, said HM18 course director Dustin Smith, MD, SFHM, of Emory University, Atlanta. “We feel strongly that all offerings at the conference are ‘must-sees,’ and it’s why we offer repeat sessions of what we predict will be the most popular talks overall. Since there are so many good sessions competing for attendees at the same time, we wanted to make sure we offered these repeat sessions of common, high-yield clinical topics.”
The Repeated Sessions track is set for April 10, and runs a full day. The track includes these dynamic sessions:
- Updates in congestive heart failure: Pablo Quintero, MD; 11-11:40 a.m.
- He-who-shall-not-be-named: Updates in sepsis and critical care: Patricia Kritek, MD, EdM; 11:50 a.m.-12:30 p.m.
- Not true love’s kiss? Updates in infectious disease: John Sanders, MD, MPHTM; 2:50-3:30 p.m.
- Updates in acute coronary syndrome: Jeff Trost, MD; 3:40-4:20 p.m.
- Waiting in line for ‘It’s a Small World’ and other things we do for no reason: Tony Breu, MD, FHM; 4:30-5:10 p.m.
- “The Mad Hatter”: Updates in delirium: Ethan Cumbler, MD, FHM; 5:20-6:00 p.m.
In addition to the sepsis update in the Repeated Sessions track, Dr. Smith noted that sepsis will also be the topic of a pre-course offering (April 8, 8:15 a.m.-4:50 p.m.). “The topic of sepsis remains a hot item in hospital medicine,” he said.
“I’d also like to highlight a new pre-course offering this year – ‘Keep your finger on the pulse: Cardiology update for the hospitalist’ (April 8, 8:30 a.m.-4:50 p.m.),” he said. “Many of our pre-course offerings are carry-overs from previous years due to ongoing great success with the individual pre-courses themselves. Although we have had a cardiology pre-course in our lineup of offerings in the past, we chose to offer a freshly redesigned pre-course in cardiology this year to round out the lineup of pre-course offerings and to keep things fresh.”
The “Stump the attentive (not absent-minded) professor” sessions on clinical unknowns in the Diagnostics Reasoning track are also must-sees, Dr. Smith said. So much so, that SHM is offering two of them this year (April 9, 2:00-2:40 p.m.; 3:45-4:25 p.m.).
Dr. Smith’s codirector Kathleen Finn, MD, MPhil, SFHM, also has a few personal favorites on the education program.
“I know the talks in the ‘Seasoning your career track’ will be great,” said Dr. Finn, a hospitalist at Massachusetts General Hospital, Boston. “This new track provides mid-career hospitalists (and new hospitalists) ideas in how to continue to make their career enjoyable and stimulating. It includes talks on how to advance in a leadership position, use emotional intelligence to achieve success, prevent burnout or design your groups schedule so it doesn’t rule your life.”
The board weighs in
The 2018 HM18 line-up garnered an enthusiastic thumbs-up from The Hospitalist’s editorial advisory board. We polled these experts for their 2018 “must-see” sessions, and they responded with a selection that spans the meeting’s wide-ranging offerings.
1. Leadership essentials for success in hospital medicine (April 9, 10:35 a.m.-12:05 p.m.)
Amit Vashist, MD, MBA, FHM, system chair, hospitalist division, Mountain State Health Alliance, Virginia/Tennessee, is especially excited about this session, intended to help hospitalists assume leadership roles.
“Given the ever-expanding footprint of hospitalists inside the hospitals and beyond, and the way they are being called upon to be the drivers of an increasingly value-based care, I believe it is imperative for every hospitalist provider – regardless of being in a leadership role or not – to have a fundamental understanding of the leadership nuances pertaining specifically to hospital medicine in order to optimally leverage their skill set to drive transformational changes in the health care arena,” he said. “This primer on leadership essentials should pique the interest of the hospitalists further towards developing a deeper appreciation of some of the leadership dimensions must-haves in the realm of hospital medicine.”
Raj Sehgal, MD, FHM, clinical associate professor of medicine, University of Texas Health Sciences Center at San Antonio, pegged communication and behavioral medicine as two top picks.
2. Do you have a minute to talk? Peer-to-peer feedback (April 9, 2:50-4:20 p.m.)
“Those of us in academic settings spend a lot of time thinking about giving feedback to – and receiving feedback from – students and residents, but some of the most valuable feedback we can get is from our coworkers,” he said. “Many hospitalist groups are actively working on ways for their providers to learn from each other, such as peer observations, and this session should help in guiding some of those programs.”
3. Through the looking glass: A psychiatrist’s tricks for inpatient acute behavioral emergencies (April 10, 2:50-3:50 p.m.)
“Even for a seasoned hospitalist who never breaks a sweat treating the most acutely medically ill patients, the acutely psychotic (or agitated, or suicidal) patient can provoke significant anxiety,” Dr. Sehgal said. “The opportunity to gain another couple of ‘tools’ to add to our kit for these patients should help alleviate that feeling.”
No need for an academic meeting to be boring, said Weijen Chang, MD, SFHM, chief of pediatric hospital medicine at Baystate Children’s Hospital, Springfield, Mass.
4. Can we just stick to the “Bare Necessities”? – Things we do for no reason (April 9, 10:35-11:35 a.m.)
5. “Mirror, Mirror on the Wall”: Which articles are the fairest of them all? Top pediatric updates (April 10, 5:45-6:45 p.m.)
“I’d say Dr. Lenny Feldman’s [SFHM] ‘Things we do for no reason’ is a must-see. Lenny is a master at simplifying complex issues and communicating them in an easily understood manner, and he’s quite entertaining,” Dr. Chang said. “And of course, another must-see is Top Pediatric Updates. It is entertaining, educational, and we almost got thrown out last year for bringing beer!”
Sarah Stella, MD, FHM, a hospitalist at Denver Health, had a hard time choosing between the many interesting offerings. “There are quite a few great sessions this year that I’m interested in, but these are my top picks:”
6. Convert your everyday work into scholarship (and get it funded) (April 9, 1:35-2:35 p.m.)
“By virtue of their daily clinical and quality improvement/committee work, many hospitalists are well on their way to generating scholarship and funding, but are unsure how to make this conversion,” she said. “This workshop is a must for academic hospitalists working toward promotion who want a framework and tangible steps on how to get credit for what they are already doing.”
7. “Heigh ho, heigh ho,” it’s off to changing roles mid-career we go (April 11, 8:20-9:00 a.m.)
“Part of what attracts many of us to hospital medicine in the first place is the versatility of what we do and the ability to diversify based on our interests. I think this is a must-see for mid-career hospitalists like myself, or really any hospitalist dreaming of reinventing oneself.”
8. Winning hearts and minds at the bedside: Battling unconscious bias through cultural humility (April 11, 9:10-9:50 a.m.)
“Recognizing and confronting our implicit biases and how they affect patient-physician interactions is hard but incredibly important work,” Dr. Stella said. “I’ll definitely be attending this session by Aziz Ansari, DO, SFHM, to learn how to improve my relationship (and hence outcomes) with my patients.”
Harry (Hyung) Cho, MD, FHM, assistant professor of medicine and director of quality, safety, and value, division of hospital medicine, Mount Sinai Hospital, New York, had some diverse choices.
9. Being female in hospital medicine: Overcoming individual and institutional barriers in the workplace (April 9, 12:40-2:15 p.m.)
“This is a very timely, very important topic in the news and I think it will draw a lot of people,” he said.
10. Every patient tells a story and the art of diagnosis (April 9, 2:55-3:35 p.m.)
“The presenter is Dr. Lisa Sanders, who writes the ‘Diagnosis’ column for the New York Times and is a Yale University faculty member. She’s a great speaker and, incidentally, was a consultant on the TV show, ‘House, MD.’ ”
Raman Palabindala, MD, FHM, a hospitalist at the University of Mississippi Medical Center, Jackson, thinks the most important session at HM18 is the annual update.
11. Update in hospital medicine (April 10, 1:40-2:40 p.m.)“Almost every year, this is the most high energy presentation, and I don’t think I ever missed this session, no matter who is the presenter is,” he said. “As physicians, I think we need this update every year, and this is the best single hour where we can learn a lot as a hospitalist related to hospital medicine. This is the most concentrated extract of the entire meeting. What I learned about the behind scenes efforts up to 50-100 hours of work – why not we take advantage of this session.”
Lonika Sood, MD, FHM of the department of hospital medicine, Aurora BayCare Medical Center, Green Bay, Wis., has a passion for both leadership and scholarship, and her choices reflect that interest.
12. How to write a winning abstract (April 11, 7:30-8:30 a.m.)
13. Leadership positions in medical education: How to break into the field (April 11, 11:40 a.m.-12:20 p.m.)
14. Serious illness communication: A skills-based workshop (April 11, 8:00-9:30 a.m.)
“I would recommend all of those, especially for early-career hospitalists. And, having enjoyed and learned a lot from the workshops at HM17, I would highly recommend checking out a few that will help polish your communications – a much-needed skill in hospital medicine,” she said.
Finally, don’t just pick up another embroidered mouse ear hat on your way out. The best HM18 souvenir is taking back the knowledge you gained and – as Dr. Sood said – there’s a session for that.
15. How to bring the things you learn at SHM back to your institution: Advocating for high value care on hospital committees (April 11, 8:00-9:30 a.m.).
For more information on the HM18 education sessions, check the latest version of the conference schedule at http://shmannualconference.org/conference-schedule.
Welcome to Hospital Medicine 2018, the second-happiest place in Orlando – at least for hospitalists who want to be in the know.
The 2018 education program is a ride through the diverse world of hospital medicine, with sessions ranging from clinical updates to cutting-edge techniques, communication tools, building a satisfying career, and finding your way through tangles of red tape and policy.
Two tracks new for 2018 hone in on managing alternative providers and palliative care.
The half-day NP/PA track (beginning April 11 at 7:30 a.m.) recognizes these practitioners for their crucial roles in hospital medicine care delivery. Among the discussions aimed at hospitalists: Best practices in provider utilization and collaboration; supervision vs. collaboration; and challenging situations when working with mid-level providers.
The palliative care track (also a half day, starting April 11 at 10 a.m.) recognizes the crucial role hospitalists play in optimizing end-of-life care. Sessions will help hospitalists understand that role, and guide them in managing pain and other symptoms commonly encountered during this transitional time.
As for the rest of the meeting, picking favorites is as tough as picking between Disney’s Big Thunder Railroad and Splash Mountain, said HM18 course director Dustin Smith, MD, SFHM, of Emory University, Atlanta. “We feel strongly that all offerings at the conference are ‘must-sees,’ and it’s why we offer repeat sessions of what we predict will be the most popular talks overall. Since there are so many good sessions competing for attendees at the same time, we wanted to make sure we offered these repeat sessions of common, high-yield clinical topics.”
The Repeated Sessions track is set for April 10, and runs a full day. The track includes these dynamic sessions:
- Updates in congestive heart failure: Pablo Quintero, MD; 11-11:40 a.m.
- He-who-shall-not-be-named: Updates in sepsis and critical care: Patricia Kritek, MD, EdM; 11:50 a.m.-12:30 p.m.
- Not true love’s kiss? Updates in infectious disease: John Sanders, MD, MPHTM; 2:50-3:30 p.m.
- Updates in acute coronary syndrome: Jeff Trost, MD; 3:40-4:20 p.m.
- Waiting in line for ‘It’s a Small World’ and other things we do for no reason: Tony Breu, MD, FHM; 4:30-5:10 p.m.
- “The Mad Hatter”: Updates in delirium: Ethan Cumbler, MD, FHM; 5:20-6:00 p.m.
In addition to the sepsis update in the Repeated Sessions track, Dr. Smith noted that sepsis will also be the topic of a pre-course offering (April 8, 8:15 a.m.-4:50 p.m.). “The topic of sepsis remains a hot item in hospital medicine,” he said.
“I’d also like to highlight a new pre-course offering this year – ‘Keep your finger on the pulse: Cardiology update for the hospitalist’ (April 8, 8:30 a.m.-4:50 p.m.),” he said. “Many of our pre-course offerings are carry-overs from previous years due to ongoing great success with the individual pre-courses themselves. Although we have had a cardiology pre-course in our lineup of offerings in the past, we chose to offer a freshly redesigned pre-course in cardiology this year to round out the lineup of pre-course offerings and to keep things fresh.”
The “Stump the attentive (not absent-minded) professor” sessions on clinical unknowns in the Diagnostics Reasoning track are also must-sees, Dr. Smith said. So much so, that SHM is offering two of them this year (April 9, 2:00-2:40 p.m.; 3:45-4:25 p.m.).
Dr. Smith’s codirector Kathleen Finn, MD, MPhil, SFHM, also has a few personal favorites on the education program.
“I know the talks in the ‘Seasoning your career track’ will be great,” said Dr. Finn, a hospitalist at Massachusetts General Hospital, Boston. “This new track provides mid-career hospitalists (and new hospitalists) ideas in how to continue to make their career enjoyable and stimulating. It includes talks on how to advance in a leadership position, use emotional intelligence to achieve success, prevent burnout or design your groups schedule so it doesn’t rule your life.”
The board weighs in
The 2018 HM18 line-up garnered an enthusiastic thumbs-up from The Hospitalist’s editorial advisory board. We polled these experts for their 2018 “must-see” sessions, and they responded with a selection that spans the meeting’s wide-ranging offerings.
1. Leadership essentials for success in hospital medicine (April 9, 10:35 a.m.-12:05 p.m.)
Amit Vashist, MD, MBA, FHM, system chair, hospitalist division, Mountain State Health Alliance, Virginia/Tennessee, is especially excited about this session, intended to help hospitalists assume leadership roles.
“Given the ever-expanding footprint of hospitalists inside the hospitals and beyond, and the way they are being called upon to be the drivers of an increasingly value-based care, I believe it is imperative for every hospitalist provider – regardless of being in a leadership role or not – to have a fundamental understanding of the leadership nuances pertaining specifically to hospital medicine in order to optimally leverage their skill set to drive transformational changes in the health care arena,” he said. “This primer on leadership essentials should pique the interest of the hospitalists further towards developing a deeper appreciation of some of the leadership dimensions must-haves in the realm of hospital medicine.”
Raj Sehgal, MD, FHM, clinical associate professor of medicine, University of Texas Health Sciences Center at San Antonio, pegged communication and behavioral medicine as two top picks.
2. Do you have a minute to talk? Peer-to-peer feedback (April 9, 2:50-4:20 p.m.)
“Those of us in academic settings spend a lot of time thinking about giving feedback to – and receiving feedback from – students and residents, but some of the most valuable feedback we can get is from our coworkers,” he said. “Many hospitalist groups are actively working on ways for their providers to learn from each other, such as peer observations, and this session should help in guiding some of those programs.”
3. Through the looking glass: A psychiatrist’s tricks for inpatient acute behavioral emergencies (April 10, 2:50-3:50 p.m.)
“Even for a seasoned hospitalist who never breaks a sweat treating the most acutely medically ill patients, the acutely psychotic (or agitated, or suicidal) patient can provoke significant anxiety,” Dr. Sehgal said. “The opportunity to gain another couple of ‘tools’ to add to our kit for these patients should help alleviate that feeling.”
No need for an academic meeting to be boring, said Weijen Chang, MD, SFHM, chief of pediatric hospital medicine at Baystate Children’s Hospital, Springfield, Mass.
4. Can we just stick to the “Bare Necessities”? – Things we do for no reason (April 9, 10:35-11:35 a.m.)
5. “Mirror, Mirror on the Wall”: Which articles are the fairest of them all? Top pediatric updates (April 10, 5:45-6:45 p.m.)
“I’d say Dr. Lenny Feldman’s [SFHM] ‘Things we do for no reason’ is a must-see. Lenny is a master at simplifying complex issues and communicating them in an easily understood manner, and he’s quite entertaining,” Dr. Chang said. “And of course, another must-see is Top Pediatric Updates. It is entertaining, educational, and we almost got thrown out last year for bringing beer!”
Sarah Stella, MD, FHM, a hospitalist at Denver Health, had a hard time choosing between the many interesting offerings. “There are quite a few great sessions this year that I’m interested in, but these are my top picks:”
6. Convert your everyday work into scholarship (and get it funded) (April 9, 1:35-2:35 p.m.)
“By virtue of their daily clinical and quality improvement/committee work, many hospitalists are well on their way to generating scholarship and funding, but are unsure how to make this conversion,” she said. “This workshop is a must for academic hospitalists working toward promotion who want a framework and tangible steps on how to get credit for what they are already doing.”
7. “Heigh ho, heigh ho,” it’s off to changing roles mid-career we go (April 11, 8:20-9:00 a.m.)
“Part of what attracts many of us to hospital medicine in the first place is the versatility of what we do and the ability to diversify based on our interests. I think this is a must-see for mid-career hospitalists like myself, or really any hospitalist dreaming of reinventing oneself.”
8. Winning hearts and minds at the bedside: Battling unconscious bias through cultural humility (April 11, 9:10-9:50 a.m.)
“Recognizing and confronting our implicit biases and how they affect patient-physician interactions is hard but incredibly important work,” Dr. Stella said. “I’ll definitely be attending this session by Aziz Ansari, DO, SFHM, to learn how to improve my relationship (and hence outcomes) with my patients.”
Harry (Hyung) Cho, MD, FHM, assistant professor of medicine and director of quality, safety, and value, division of hospital medicine, Mount Sinai Hospital, New York, had some diverse choices.
9. Being female in hospital medicine: Overcoming individual and institutional barriers in the workplace (April 9, 12:40-2:15 p.m.)
“This is a very timely, very important topic in the news and I think it will draw a lot of people,” he said.
10. Every patient tells a story and the art of diagnosis (April 9, 2:55-3:35 p.m.)
“The presenter is Dr. Lisa Sanders, who writes the ‘Diagnosis’ column for the New York Times and is a Yale University faculty member. She’s a great speaker and, incidentally, was a consultant on the TV show, ‘House, MD.’ ”
Raman Palabindala, MD, FHM, a hospitalist at the University of Mississippi Medical Center, Jackson, thinks the most important session at HM18 is the annual update.
11. Update in hospital medicine (April 10, 1:40-2:40 p.m.)“Almost every year, this is the most high energy presentation, and I don’t think I ever missed this session, no matter who is the presenter is,” he said. “As physicians, I think we need this update every year, and this is the best single hour where we can learn a lot as a hospitalist related to hospital medicine. This is the most concentrated extract of the entire meeting. What I learned about the behind scenes efforts up to 50-100 hours of work – why not we take advantage of this session.”
Lonika Sood, MD, FHM of the department of hospital medicine, Aurora BayCare Medical Center, Green Bay, Wis., has a passion for both leadership and scholarship, and her choices reflect that interest.
12. How to write a winning abstract (April 11, 7:30-8:30 a.m.)
13. Leadership positions in medical education: How to break into the field (April 11, 11:40 a.m.-12:20 p.m.)
14. Serious illness communication: A skills-based workshop (April 11, 8:00-9:30 a.m.)
“I would recommend all of those, especially for early-career hospitalists. And, having enjoyed and learned a lot from the workshops at HM17, I would highly recommend checking out a few that will help polish your communications – a much-needed skill in hospital medicine,” she said.
Finally, don’t just pick up another embroidered mouse ear hat on your way out. The best HM18 souvenir is taking back the knowledge you gained and – as Dr. Sood said – there’s a session for that.
15. How to bring the things you learn at SHM back to your institution: Advocating for high value care on hospital committees (April 11, 8:00-9:30 a.m.).
For more information on the HM18 education sessions, check the latest version of the conference schedule at http://shmannualconference.org/conference-schedule.
Welcome to Hospital Medicine 2018, the second-happiest place in Orlando – at least for hospitalists who want to be in the know.
The 2018 education program is a ride through the diverse world of hospital medicine, with sessions ranging from clinical updates to cutting-edge techniques, communication tools, building a satisfying career, and finding your way through tangles of red tape and policy.
Two tracks new for 2018 hone in on managing alternative providers and palliative care.
The half-day NP/PA track (beginning April 11 at 7:30 a.m.) recognizes these practitioners for their crucial roles in hospital medicine care delivery. Among the discussions aimed at hospitalists: Best practices in provider utilization and collaboration; supervision vs. collaboration; and challenging situations when working with mid-level providers.
The palliative care track (also a half day, starting April 11 at 10 a.m.) recognizes the crucial role hospitalists play in optimizing end-of-life care. Sessions will help hospitalists understand that role, and guide them in managing pain and other symptoms commonly encountered during this transitional time.
As for the rest of the meeting, picking favorites is as tough as picking between Disney’s Big Thunder Railroad and Splash Mountain, said HM18 course director Dustin Smith, MD, SFHM, of Emory University, Atlanta. “We feel strongly that all offerings at the conference are ‘must-sees,’ and it’s why we offer repeat sessions of what we predict will be the most popular talks overall. Since there are so many good sessions competing for attendees at the same time, we wanted to make sure we offered these repeat sessions of common, high-yield clinical topics.”
The Repeated Sessions track is set for April 10, and runs a full day. The track includes these dynamic sessions:
- Updates in congestive heart failure: Pablo Quintero, MD; 11-11:40 a.m.
- He-who-shall-not-be-named: Updates in sepsis and critical care: Patricia Kritek, MD, EdM; 11:50 a.m.-12:30 p.m.
- Not true love’s kiss? Updates in infectious disease: John Sanders, MD, MPHTM; 2:50-3:30 p.m.
- Updates in acute coronary syndrome: Jeff Trost, MD; 3:40-4:20 p.m.
- Waiting in line for ‘It’s a Small World’ and other things we do for no reason: Tony Breu, MD, FHM; 4:30-5:10 p.m.
- “The Mad Hatter”: Updates in delirium: Ethan Cumbler, MD, FHM; 5:20-6:00 p.m.
In addition to the sepsis update in the Repeated Sessions track, Dr. Smith noted that sepsis will also be the topic of a pre-course offering (April 8, 8:15 a.m.-4:50 p.m.). “The topic of sepsis remains a hot item in hospital medicine,” he said.
“I’d also like to highlight a new pre-course offering this year – ‘Keep your finger on the pulse: Cardiology update for the hospitalist’ (April 8, 8:30 a.m.-4:50 p.m.),” he said. “Many of our pre-course offerings are carry-overs from previous years due to ongoing great success with the individual pre-courses themselves. Although we have had a cardiology pre-course in our lineup of offerings in the past, we chose to offer a freshly redesigned pre-course in cardiology this year to round out the lineup of pre-course offerings and to keep things fresh.”
The “Stump the attentive (not absent-minded) professor” sessions on clinical unknowns in the Diagnostics Reasoning track are also must-sees, Dr. Smith said. So much so, that SHM is offering two of them this year (April 9, 2:00-2:40 p.m.; 3:45-4:25 p.m.).
Dr. Smith’s codirector Kathleen Finn, MD, MPhil, SFHM, also has a few personal favorites on the education program.
“I know the talks in the ‘Seasoning your career track’ will be great,” said Dr. Finn, a hospitalist at Massachusetts General Hospital, Boston. “This new track provides mid-career hospitalists (and new hospitalists) ideas in how to continue to make their career enjoyable and stimulating. It includes talks on how to advance in a leadership position, use emotional intelligence to achieve success, prevent burnout or design your groups schedule so it doesn’t rule your life.”
The board weighs in
The 2018 HM18 line-up garnered an enthusiastic thumbs-up from The Hospitalist’s editorial advisory board. We polled these experts for their 2018 “must-see” sessions, and they responded with a selection that spans the meeting’s wide-ranging offerings.
1. Leadership essentials for success in hospital medicine (April 9, 10:35 a.m.-12:05 p.m.)
Amit Vashist, MD, MBA, FHM, system chair, hospitalist division, Mountain State Health Alliance, Virginia/Tennessee, is especially excited about this session, intended to help hospitalists assume leadership roles.
“Given the ever-expanding footprint of hospitalists inside the hospitals and beyond, and the way they are being called upon to be the drivers of an increasingly value-based care, I believe it is imperative for every hospitalist provider – regardless of being in a leadership role or not – to have a fundamental understanding of the leadership nuances pertaining specifically to hospital medicine in order to optimally leverage their skill set to drive transformational changes in the health care arena,” he said. “This primer on leadership essentials should pique the interest of the hospitalists further towards developing a deeper appreciation of some of the leadership dimensions must-haves in the realm of hospital medicine.”
Raj Sehgal, MD, FHM, clinical associate professor of medicine, University of Texas Health Sciences Center at San Antonio, pegged communication and behavioral medicine as two top picks.
2. Do you have a minute to talk? Peer-to-peer feedback (April 9, 2:50-4:20 p.m.)
“Those of us in academic settings spend a lot of time thinking about giving feedback to – and receiving feedback from – students and residents, but some of the most valuable feedback we can get is from our coworkers,” he said. “Many hospitalist groups are actively working on ways for their providers to learn from each other, such as peer observations, and this session should help in guiding some of those programs.”
3. Through the looking glass: A psychiatrist’s tricks for inpatient acute behavioral emergencies (April 10, 2:50-3:50 p.m.)
“Even for a seasoned hospitalist who never breaks a sweat treating the most acutely medically ill patients, the acutely psychotic (or agitated, or suicidal) patient can provoke significant anxiety,” Dr. Sehgal said. “The opportunity to gain another couple of ‘tools’ to add to our kit for these patients should help alleviate that feeling.”
No need for an academic meeting to be boring, said Weijen Chang, MD, SFHM, chief of pediatric hospital medicine at Baystate Children’s Hospital, Springfield, Mass.
4. Can we just stick to the “Bare Necessities”? – Things we do for no reason (April 9, 10:35-11:35 a.m.)
5. “Mirror, Mirror on the Wall”: Which articles are the fairest of them all? Top pediatric updates (April 10, 5:45-6:45 p.m.)
“I’d say Dr. Lenny Feldman’s [SFHM] ‘Things we do for no reason’ is a must-see. Lenny is a master at simplifying complex issues and communicating them in an easily understood manner, and he’s quite entertaining,” Dr. Chang said. “And of course, another must-see is Top Pediatric Updates. It is entertaining, educational, and we almost got thrown out last year for bringing beer!”
Sarah Stella, MD, FHM, a hospitalist at Denver Health, had a hard time choosing between the many interesting offerings. “There are quite a few great sessions this year that I’m interested in, but these are my top picks:”
6. Convert your everyday work into scholarship (and get it funded) (April 9, 1:35-2:35 p.m.)
“By virtue of their daily clinical and quality improvement/committee work, many hospitalists are well on their way to generating scholarship and funding, but are unsure how to make this conversion,” she said. “This workshop is a must for academic hospitalists working toward promotion who want a framework and tangible steps on how to get credit for what they are already doing.”
7. “Heigh ho, heigh ho,” it’s off to changing roles mid-career we go (April 11, 8:20-9:00 a.m.)
“Part of what attracts many of us to hospital medicine in the first place is the versatility of what we do and the ability to diversify based on our interests. I think this is a must-see for mid-career hospitalists like myself, or really any hospitalist dreaming of reinventing oneself.”
8. Winning hearts and minds at the bedside: Battling unconscious bias through cultural humility (April 11, 9:10-9:50 a.m.)
“Recognizing and confronting our implicit biases and how they affect patient-physician interactions is hard but incredibly important work,” Dr. Stella said. “I’ll definitely be attending this session by Aziz Ansari, DO, SFHM, to learn how to improve my relationship (and hence outcomes) with my patients.”
Harry (Hyung) Cho, MD, FHM, assistant professor of medicine and director of quality, safety, and value, division of hospital medicine, Mount Sinai Hospital, New York, had some diverse choices.
9. Being female in hospital medicine: Overcoming individual and institutional barriers in the workplace (April 9, 12:40-2:15 p.m.)
“This is a very timely, very important topic in the news and I think it will draw a lot of people,” he said.
10. Every patient tells a story and the art of diagnosis (April 9, 2:55-3:35 p.m.)
“The presenter is Dr. Lisa Sanders, who writes the ‘Diagnosis’ column for the New York Times and is a Yale University faculty member. She’s a great speaker and, incidentally, was a consultant on the TV show, ‘House, MD.’ ”
Raman Palabindala, MD, FHM, a hospitalist at the University of Mississippi Medical Center, Jackson, thinks the most important session at HM18 is the annual update.
11. Update in hospital medicine (April 10, 1:40-2:40 p.m.)“Almost every year, this is the most high energy presentation, and I don’t think I ever missed this session, no matter who is the presenter is,” he said. “As physicians, I think we need this update every year, and this is the best single hour where we can learn a lot as a hospitalist related to hospital medicine. This is the most concentrated extract of the entire meeting. What I learned about the behind scenes efforts up to 50-100 hours of work – why not we take advantage of this session.”
Lonika Sood, MD, FHM of the department of hospital medicine, Aurora BayCare Medical Center, Green Bay, Wis., has a passion for both leadership and scholarship, and her choices reflect that interest.
12. How to write a winning abstract (April 11, 7:30-8:30 a.m.)
13. Leadership positions in medical education: How to break into the field (April 11, 11:40 a.m.-12:20 p.m.)
14. Serious illness communication: A skills-based workshop (April 11, 8:00-9:30 a.m.)
“I would recommend all of those, especially for early-career hospitalists. And, having enjoyed and learned a lot from the workshops at HM17, I would highly recommend checking out a few that will help polish your communications – a much-needed skill in hospital medicine,” she said.
Finally, don’t just pick up another embroidered mouse ear hat on your way out. The best HM18 souvenir is taking back the knowledge you gained and – as Dr. Sood said – there’s a session for that.
15. How to bring the things you learn at SHM back to your institution: Advocating for high value care on hospital committees (April 11, 8:00-9:30 a.m.).
For more information on the HM18 education sessions, check the latest version of the conference schedule at http://shmannualconference.org/conference-schedule.
Could guselkumab be a disease-modifying agent in plaque psoriasis?
SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?
At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.
“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”
VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.
Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).
At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.
Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.
“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”
The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.
“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”
“I admit, I did at one time believe this story about disease modification,” said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. “But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you’re modifying disease?”
Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.
“We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don’t know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue.”
Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
SOURCE: Gordon K et al. AAD 2018 Abstract 6748.
SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?
At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.
“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”
VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.
Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).
At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.
Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.
“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”
The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.
“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”
“I admit, I did at one time believe this story about disease modification,” said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. “But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you’re modifying disease?”
Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.
“We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don’t know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue.”
Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
SOURCE: Gordon K et al. AAD 2018 Abstract 6748.
SAN DIEGO – Could some of the monoclonal antibodies posting striking results in psoriasis trials be doing more than quelling symptoms?
At least some researchers think so, as evidenced by a brief discussion during AAD 2018 of the durable responses some guselkumab-treated patients achieved in the VOYAGE 2 trial.
“Isn’t this amazing?” asked Kristian Reich, MD, after listening to several late-breaking, solidly positive trials of monoclonal antibodies for plaque psoriasis. “I think it’s fantastic that we now have drugs that clear 50% or more of a patient’s psoriasis. We should not be taking this for granted.”
VOYAGE 2 was an active-comparator, placebo-controlled study that pitted guselkumab against adalimumab (Humira) and placebo in a crossover design. It enrolled about 900 patients with moderate to severe plaque psoriasis.
Patients were randomized to 28 weeks of treatment in three arms: guselkumab 100 mg (weeks 0 and 4, then every 8 weeks); placebo for 16 weeks, then guselkumab 100 mg at weeks 16 and 20; or adalimumab (80 mg at week 0, then 40 mg at week 1, and every 2 weeks through week 23).
At 28 weeks, a total of 375 Psoriasis Area and Severity Index (PASI) 90 treatment responders in the guselkumab arm were rerandomized to either stay on guselkumab (n = 193) or withdraw to placebo (n = 182) until they lost whatever response they had gained at that point.
Although PASI 90 responses were much better maintained in the guselkumab group that stayed on therapy, they did not fade quickly. And although 89% of the maintenance group maintained their PASI 90 response at 48 weeks, 37% of those in the withdrawal group had still maintained that 90% improvement over baseline by 48 weeks.
“Is this drug opening the door to disease modification? Is it doing something that allows disease control even if we stop the therapy? This is what we see happening when we stop the drug in PASI 90 responders. Yes, the disease is coming back, but the median time to recurrence is more than 3 months.”
The cytokine profiles of these patients appear to support this idea, Dr. Reich contended.
“In the first 28 weeks, when they were all receiving the drug, their IL-23, IL-17A, and IL-17F levels were all going down rapidly. But this is the interesting part. In some patients who maintained their PASI response after withdrawal, those cytokines continued to be suppressed. They rose in patients who lost response. We need to do more tests to understand what’s going on here, but I do think the door is opening to what I would call disease modification.”
“I admit, I did at one time believe this story about disease modification,” said Dr. Papp, founder and president of Probity Medical Research in Waterloo, Ont. “But now I think we are simply seeing a pharmacokinetic effect. How can you reconcile what is clearly a pharmacologic and mechanistic perspective with this suggestion that you’re modifying disease?”
Session moderator Hensin Tsao, MD, suggested that the answer might lie in some unknown in-between territory.
“We do see about 10%-20% of patients in whom drug-free remission is not explained by pharmacokinetics. In some patients, the drug is long gone, and they are still clear of disease – and we don’t know how to talk about those patients yet. But we do need to study them because, for those people, clearly it is not a [pharmacokinetic] issue.”
Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
SOURCE: Gordon K et al. AAD 2018 Abstract 6748.
REPORTING FROM AAD 2018
Key clinical point: Guselkumab shows some signs of having a disease-modifying effect in moderate to severe psoriasis after 28 weeks of treatment.
Major finding: A total of 37% of patients who withdrew from guselkumab at 28 weeks had still maintained PASI 90 improvement over baseline at 48 weeks.
Study details: An analysis of randomization to drug continuation vs. withdrawal in 375 patients with PASI 90 response to guselkumab in the VOYAGE 2 trial.
Disclosures: Dr. Reich disclosed financial relationships with numerous pharmaceutical companies, including Janssen, which manufactures guselkumab. Dr. Papp also disclosed multiple relationships with drug manufacturers.
Source: Gordon K et al. AAD 2018 Abstract 6748.
Ustekinumab quells aortic inflammation in patients with severe psoriasis
SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.
Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.
For the past decade, researchers have worked on the assumption that the chronic systemic inflammation of severe psoriasis overlaps with similar inflammatory pathways that drive atherosclerosis, plaques that rupture, and cardiovascular events.
Recently, they have employed fluorodeoxyglucose positron emission tomography (FDG-PET) to confirm some of this. Studies in 2011, 2015, and 2017 confirm that patients with severe plaque psoriasis can develop diffuse vascular inflammation with increased noncalcified coronary artery plaques. These more fragile plaques are the type that are prone to rupture and cause cardiovascular events, Dr. Gelfand said.
“In these studies, the more imaging signal we saw in the aorta, the higher the risk of a future cardiovascular event. In fact, we determined that patients with severe psoriasis can have increased aortic inflammation equivalent to a decade of aging. As your PASI [Psoriasis Area and Severity Index] score goes up, so does the amount of aortic inflammation. The anatomic consequence is that people develop a high risk of atherosclerotic plaques, and a higher rate of noncalcified coronary plaques that are more likely to lead to these events.”
The VIP-U study was conceived to examine whether calming psoriatic inflammation with ustekinumab (Stelara), an anti interleukin-12 and -23 antibody, could also improve vascular inflammation as measured by FDG-PET. The small study comprised 43 patients, half of whom received placebo and half of whom received two injections of ustekinumab: 45 or 90 mg depending on weight, at baseline and at week 4. There was an imaging assessment at week 12, after which the placebo patients crossed over to open-label ustekinumab every 2 weeks. Everyone was followed out to 64 weeks.
Dr. Gelfand reported the 12-week data; the 64-week data will be forthcoming later this year, he said.
The patients were typical for such a study, with a mean age of about 43 and a mean disease duration of 18 years. The mean body surface area was about 25%, and the mean PASI was 20. Most had been on prior therapy, including phototherapy, oral agents, and biologics.
Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.
However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”
The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.
“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”
To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].
The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.
SOURCE: Gelfand J et al. AAD 2018 Abstract 6645
SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.
Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.
For the past decade, researchers have worked on the assumption that the chronic systemic inflammation of severe psoriasis overlaps with similar inflammatory pathways that drive atherosclerosis, plaques that rupture, and cardiovascular events.
Recently, they have employed fluorodeoxyglucose positron emission tomography (FDG-PET) to confirm some of this. Studies in 2011, 2015, and 2017 confirm that patients with severe plaque psoriasis can develop diffuse vascular inflammation with increased noncalcified coronary artery plaques. These more fragile plaques are the type that are prone to rupture and cause cardiovascular events, Dr. Gelfand said.
“In these studies, the more imaging signal we saw in the aorta, the higher the risk of a future cardiovascular event. In fact, we determined that patients with severe psoriasis can have increased aortic inflammation equivalent to a decade of aging. As your PASI [Psoriasis Area and Severity Index] score goes up, so does the amount of aortic inflammation. The anatomic consequence is that people develop a high risk of atherosclerotic plaques, and a higher rate of noncalcified coronary plaques that are more likely to lead to these events.”
The VIP-U study was conceived to examine whether calming psoriatic inflammation with ustekinumab (Stelara), an anti interleukin-12 and -23 antibody, could also improve vascular inflammation as measured by FDG-PET. The small study comprised 43 patients, half of whom received placebo and half of whom received two injections of ustekinumab: 45 or 90 mg depending on weight, at baseline and at week 4. There was an imaging assessment at week 12, after which the placebo patients crossed over to open-label ustekinumab every 2 weeks. Everyone was followed out to 64 weeks.
Dr. Gelfand reported the 12-week data; the 64-week data will be forthcoming later this year, he said.
The patients were typical for such a study, with a mean age of about 43 and a mean disease duration of 18 years. The mean body surface area was about 25%, and the mean PASI was 20. Most had been on prior therapy, including phototherapy, oral agents, and biologics.
Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.
However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”
The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.
“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”
To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].
The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.
SOURCE: Gelfand J et al. AAD 2018 Abstract 6645
SAN DIEGO – A 12-week course of ustekinumab significantly reduced inflammation in the aorta – an effect on par with the benefit of statins – in patients with moderate to severe plaque psoriasis.
Whether or not the reduction in aortic inflammation will translate into a reduction in cardiovascular risk remains to be determined, but investigators are very encouraged by the results of the Vascular Inflammation in Psoriasis-Ustekinumab (VIP-U) study, Joel M. Gelfand, MD, said at the annual meeting of the American Academy of Dermatology.
For the past decade, researchers have worked on the assumption that the chronic systemic inflammation of severe psoriasis overlaps with similar inflammatory pathways that drive atherosclerosis, plaques that rupture, and cardiovascular events.
Recently, they have employed fluorodeoxyglucose positron emission tomography (FDG-PET) to confirm some of this. Studies in 2011, 2015, and 2017 confirm that patients with severe plaque psoriasis can develop diffuse vascular inflammation with increased noncalcified coronary artery plaques. These more fragile plaques are the type that are prone to rupture and cause cardiovascular events, Dr. Gelfand said.
“In these studies, the more imaging signal we saw in the aorta, the higher the risk of a future cardiovascular event. In fact, we determined that patients with severe psoriasis can have increased aortic inflammation equivalent to a decade of aging. As your PASI [Psoriasis Area and Severity Index] score goes up, so does the amount of aortic inflammation. The anatomic consequence is that people develop a high risk of atherosclerotic plaques, and a higher rate of noncalcified coronary plaques that are more likely to lead to these events.”
The VIP-U study was conceived to examine whether calming psoriatic inflammation with ustekinumab (Stelara), an anti interleukin-12 and -23 antibody, could also improve vascular inflammation as measured by FDG-PET. The small study comprised 43 patients, half of whom received placebo and half of whom received two injections of ustekinumab: 45 or 90 mg depending on weight, at baseline and at week 4. There was an imaging assessment at week 12, after which the placebo patients crossed over to open-label ustekinumab every 2 weeks. Everyone was followed out to 64 weeks.
Dr. Gelfand reported the 12-week data; the 64-week data will be forthcoming later this year, he said.
The patients were typical for such a study, with a mean age of about 43 and a mean disease duration of 18 years. The mean body surface area was about 25%, and the mean PASI was 20. Most had been on prior therapy, including phototherapy, oral agents, and biologics.
Unsurprisingly, ustekinumab was significantly more effective than placebo in treating the psoriasis. At week 12, 10% of the placebo patients had achieved a PASI 75, compared with 77% of the ustekinumab patients. A Physicians Global Assessment (PGA) score of clear or almost clear occurred in 10% of those taking placebo and 64% of those taking the biologic.
However, the drug was also highly effective in reducing total aortic inflammation, Dr. Gelfand said. “In just 12 weeks, we saw a 6.6% reduction in total aortic inflammation among those taking ustekinumab, but a 12.1% increase in inflammation among those taking placebo. When you compare the delta, you see a highly statistically significant improvement in aortic inflammation in ustekinumab-treated patients, with the effect size similar to statin therapy.”
The benefit may be a class-associated one. Two recent similar studies of adalimumab, a tumor necrosis factor–alpha inhibitor, failed to find any improvement in vascular inflammation, compared with placebo.
“We need more information about the longer-term effects of ustekinumab treatment, as well as cardiometabolic biomarkers, and these are currently underway,” Dr. Gelfand said. “We also need additional trials to determine if this effect is due to the inhibition of IL-12, IL-23, or a combination. Cardiovascular studies will be necessary to fully determine the clinical implications of our findings.”
To refer a patient into the VIP studies, call 215-662-SKIN or email [email protected].
The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand reported no financial disclosures.
SOURCE: Gelfand J et al. AAD 2018 Abstract 6645
REPORTING FROM AAD 2018
Key clinical point:
Major finding: Aortic inflammation decreased by 6.6% in those taking ustekinumab, but increased by 12.1% in those taking placebo.
Study details: The randomized trial comprised 43 patients.
Disclosures: The National Institutes of Health and University of Pennsylvania sponsored the study. Dr. Gelfand made no financial disclosures.
Source: Gelfand J et al. AAD 2018 Abstract 6645.
Dual kinase inhibitor performs well in its first safety, efficacy study for atopic dermatitis
SAN DIEGO – A novel molecule that inhibits two major inflammatory pathways acquitted itself well in its first safety and efficacy clinical trial in patients with moderate to severe atopic dermatitis.
After 29 days, 100% of those taking the highest dose of the molecule, ASN002, achieved a 50% improvement in skin involvement.
“This is an interesting molecule,” Robert Bissonnette, MD, said at the annual meeting of the American Academy of Dermatology. “By targeting the entire JAK family, it inhibits cytokine signaling through IL-4 [interleukin-4], IL-13, IL-23, and thymic stromal lymphopoietin,” which plays a role in maturing T cells. The SYK inhibition targets IL-17, increases the terminal differentiation of keratinocytes, and inhibits B-cell signaling.
Dr. Bissonnette, president of Innovaderm Research presented the results in a late-breaking session at the meeting. Innovaderm designs, conducts, and analyzes dermatology clinical trials, and ran the study for Asana BioSciences.
In an Asana press release about the study results, CEO Sandeep Gupta, PhD, said that ASN002 “is the only oral compound in clinical development targeting JAK [including Tyk2] and SYK signaling, two clinically validated mechanisms.” He added that inhibition of JAK and SYK pathways “diminishes cytokine production and signaling including those mediated by Th2 and Th22 cytokines. Dysregulation of Th2 and Th22 cytokine pathways is implicated in the pathogenesis of atopic dermatitis.”
Safety was the primary endpoint in the phase 1b dose-ranging trial, but there were also several efficacy endpoints, Dr. Bissonnette said at the meeting. The study comprised 36 patients separated into three 12-patient groups. In each group, nine received the active drug every day, and three received a placebo. The first group received 20 mg ASN002 or placebo for 28 days, followed by the 14-day safety period. The next group received 40 mg ASN002 or placebo for 28 days, followed by the safety analysis. The third group followed the same treatment pattern, but received 80 mg of the drug.
All patients were aged 29-42 years. The Eczema Area and Severity Index (EASI) was imbalanced among the groups, ranging from 21 in the placebo group and 40-mg group, to 29 in the 20-mg and 80-mg groups. The Body Surface Area (BSA) index also differed between groups: 25% among the placebo patients, 45% in the 20-mg group, 32% in the 40-mg group, and 29% in the 80-mg group. The average Investigator Global Assessment (IGA) score was 3.
A pharmacokinetic analysis showed rapid uptake of the drug with a half-life of 10-14 hours depending on dose.
There were no concerning safety signals, Dr. Bissonnette said and no thromboembolic events, serious infections, or opportunistic infections. The most common adverse event was headache, which occurred at equal rates among the groups. The single serious adverse event was anxiety, which occurred in one patient taking 80 mg ASN002, 4 days after the medication was stopped, and was judged unrelated to ASN002.
There were no significant changes in any lab parameters, no changes in lipid profiles, and no hematologic abnormalities. One patient experienced an increase in creatinine phosphokinase, something that has been seen in other studies of JAK inhibitors, Dr. Bissonnette said.
The molecule performed well on secondary efficacy endpoints. By day 15, 63% of the 40-mg group and 75% of the 80-mg group had achieved EASI-50, and by day 29, these rates were 88% and 100%, respectively. These doses also performed well on the EASI-75 endpoint. By day 29, 63% of the 40-mg group and 50% of the 80-mg group had achieved a 75% improvement in EASI score.
The 40- and 80-mg groups also did well with regards to BSA improvement. By day 29, the 80-mg group had achieved a mean BSA reduction of 58%, and the 40-mg group a mean reduction of 64%. IGA tracked that improvement, with 25% of the 80-mg group and 38% of the 40-mg group achieving an IGA score of 1 or 0.
Itching responded well to ASN002, but here, the 20-mg dose threw investigators a bit of a curve ball. Pruritus decreased most in the 80-mg group (about 70% by the end of the study). But at 3 weeks, patients taking 20 mg and 40 mg were experiencing the same 30% decrease in itch. By 4 weeks, however, the scores had separated, with the 40-mg group landing at about a 40% reduction, and the 20-mg group rebounding to about a 20% reduction.
“I would say that this first trial of ASN002 showed clear efficacy in patients with moderate to severe atopic dermatitis, with rapid improvement itch and a large proportion of patients reaching EASI-50 as early as 2 weeks,” Dr. Bissonnette said.
Asana will soon initiate a phase 2b study of ASN002 in moderate to severe atopic dermatitis patients. Clinical studies in other dermatologic and autoimmune indications are under consideration, according to the company website.
Dr. Bissonnette is the president of Innovaderm Research, which was paid to run the ASN002 study.
SOURCE: Bissonnette R et al. AAD 2018, Abstract 6777
SAN DIEGO – A novel molecule that inhibits two major inflammatory pathways acquitted itself well in its first safety and efficacy clinical trial in patients with moderate to severe atopic dermatitis.
After 29 days, 100% of those taking the highest dose of the molecule, ASN002, achieved a 50% improvement in skin involvement.
“This is an interesting molecule,” Robert Bissonnette, MD, said at the annual meeting of the American Academy of Dermatology. “By targeting the entire JAK family, it inhibits cytokine signaling through IL-4 [interleukin-4], IL-13, IL-23, and thymic stromal lymphopoietin,” which plays a role in maturing T cells. The SYK inhibition targets IL-17, increases the terminal differentiation of keratinocytes, and inhibits B-cell signaling.
Dr. Bissonnette, president of Innovaderm Research presented the results in a late-breaking session at the meeting. Innovaderm designs, conducts, and analyzes dermatology clinical trials, and ran the study for Asana BioSciences.
In an Asana press release about the study results, CEO Sandeep Gupta, PhD, said that ASN002 “is the only oral compound in clinical development targeting JAK [including Tyk2] and SYK signaling, two clinically validated mechanisms.” He added that inhibition of JAK and SYK pathways “diminishes cytokine production and signaling including those mediated by Th2 and Th22 cytokines. Dysregulation of Th2 and Th22 cytokine pathways is implicated in the pathogenesis of atopic dermatitis.”
Safety was the primary endpoint in the phase 1b dose-ranging trial, but there were also several efficacy endpoints, Dr. Bissonnette said at the meeting. The study comprised 36 patients separated into three 12-patient groups. In each group, nine received the active drug every day, and three received a placebo. The first group received 20 mg ASN002 or placebo for 28 days, followed by the 14-day safety period. The next group received 40 mg ASN002 or placebo for 28 days, followed by the safety analysis. The third group followed the same treatment pattern, but received 80 mg of the drug.
All patients were aged 29-42 years. The Eczema Area and Severity Index (EASI) was imbalanced among the groups, ranging from 21 in the placebo group and 40-mg group, to 29 in the 20-mg and 80-mg groups. The Body Surface Area (BSA) index also differed between groups: 25% among the placebo patients, 45% in the 20-mg group, 32% in the 40-mg group, and 29% in the 80-mg group. The average Investigator Global Assessment (IGA) score was 3.
A pharmacokinetic analysis showed rapid uptake of the drug with a half-life of 10-14 hours depending on dose.
There were no concerning safety signals, Dr. Bissonnette said and no thromboembolic events, serious infections, or opportunistic infections. The most common adverse event was headache, which occurred at equal rates among the groups. The single serious adverse event was anxiety, which occurred in one patient taking 80 mg ASN002, 4 days after the medication was stopped, and was judged unrelated to ASN002.
There were no significant changes in any lab parameters, no changes in lipid profiles, and no hematologic abnormalities. One patient experienced an increase in creatinine phosphokinase, something that has been seen in other studies of JAK inhibitors, Dr. Bissonnette said.
The molecule performed well on secondary efficacy endpoints. By day 15, 63% of the 40-mg group and 75% of the 80-mg group had achieved EASI-50, and by day 29, these rates were 88% and 100%, respectively. These doses also performed well on the EASI-75 endpoint. By day 29, 63% of the 40-mg group and 50% of the 80-mg group had achieved a 75% improvement in EASI score.
The 40- and 80-mg groups also did well with regards to BSA improvement. By day 29, the 80-mg group had achieved a mean BSA reduction of 58%, and the 40-mg group a mean reduction of 64%. IGA tracked that improvement, with 25% of the 80-mg group and 38% of the 40-mg group achieving an IGA score of 1 or 0.
Itching responded well to ASN002, but here, the 20-mg dose threw investigators a bit of a curve ball. Pruritus decreased most in the 80-mg group (about 70% by the end of the study). But at 3 weeks, patients taking 20 mg and 40 mg were experiencing the same 30% decrease in itch. By 4 weeks, however, the scores had separated, with the 40-mg group landing at about a 40% reduction, and the 20-mg group rebounding to about a 20% reduction.
“I would say that this first trial of ASN002 showed clear efficacy in patients with moderate to severe atopic dermatitis, with rapid improvement itch and a large proportion of patients reaching EASI-50 as early as 2 weeks,” Dr. Bissonnette said.
Asana will soon initiate a phase 2b study of ASN002 in moderate to severe atopic dermatitis patients. Clinical studies in other dermatologic and autoimmune indications are under consideration, according to the company website.
Dr. Bissonnette is the president of Innovaderm Research, which was paid to run the ASN002 study.
SOURCE: Bissonnette R et al. AAD 2018, Abstract 6777
SAN DIEGO – A novel molecule that inhibits two major inflammatory pathways acquitted itself well in its first safety and efficacy clinical trial in patients with moderate to severe atopic dermatitis.
After 29 days, 100% of those taking the highest dose of the molecule, ASN002, achieved a 50% improvement in skin involvement.
“This is an interesting molecule,” Robert Bissonnette, MD, said at the annual meeting of the American Academy of Dermatology. “By targeting the entire JAK family, it inhibits cytokine signaling through IL-4 [interleukin-4], IL-13, IL-23, and thymic stromal lymphopoietin,” which plays a role in maturing T cells. The SYK inhibition targets IL-17, increases the terminal differentiation of keratinocytes, and inhibits B-cell signaling.
Dr. Bissonnette, president of Innovaderm Research presented the results in a late-breaking session at the meeting. Innovaderm designs, conducts, and analyzes dermatology clinical trials, and ran the study for Asana BioSciences.
In an Asana press release about the study results, CEO Sandeep Gupta, PhD, said that ASN002 “is the only oral compound in clinical development targeting JAK [including Tyk2] and SYK signaling, two clinically validated mechanisms.” He added that inhibition of JAK and SYK pathways “diminishes cytokine production and signaling including those mediated by Th2 and Th22 cytokines. Dysregulation of Th2 and Th22 cytokine pathways is implicated in the pathogenesis of atopic dermatitis.”
Safety was the primary endpoint in the phase 1b dose-ranging trial, but there were also several efficacy endpoints, Dr. Bissonnette said at the meeting. The study comprised 36 patients separated into three 12-patient groups. In each group, nine received the active drug every day, and three received a placebo. The first group received 20 mg ASN002 or placebo for 28 days, followed by the 14-day safety period. The next group received 40 mg ASN002 or placebo for 28 days, followed by the safety analysis. The third group followed the same treatment pattern, but received 80 mg of the drug.
All patients were aged 29-42 years. The Eczema Area and Severity Index (EASI) was imbalanced among the groups, ranging from 21 in the placebo group and 40-mg group, to 29 in the 20-mg and 80-mg groups. The Body Surface Area (BSA) index also differed between groups: 25% among the placebo patients, 45% in the 20-mg group, 32% in the 40-mg group, and 29% in the 80-mg group. The average Investigator Global Assessment (IGA) score was 3.
A pharmacokinetic analysis showed rapid uptake of the drug with a half-life of 10-14 hours depending on dose.
There were no concerning safety signals, Dr. Bissonnette said and no thromboembolic events, serious infections, or opportunistic infections. The most common adverse event was headache, which occurred at equal rates among the groups. The single serious adverse event was anxiety, which occurred in one patient taking 80 mg ASN002, 4 days after the medication was stopped, and was judged unrelated to ASN002.
There were no significant changes in any lab parameters, no changes in lipid profiles, and no hematologic abnormalities. One patient experienced an increase in creatinine phosphokinase, something that has been seen in other studies of JAK inhibitors, Dr. Bissonnette said.
The molecule performed well on secondary efficacy endpoints. By day 15, 63% of the 40-mg group and 75% of the 80-mg group had achieved EASI-50, and by day 29, these rates were 88% and 100%, respectively. These doses also performed well on the EASI-75 endpoint. By day 29, 63% of the 40-mg group and 50% of the 80-mg group had achieved a 75% improvement in EASI score.
The 40- and 80-mg groups also did well with regards to BSA improvement. By day 29, the 80-mg group had achieved a mean BSA reduction of 58%, and the 40-mg group a mean reduction of 64%. IGA tracked that improvement, with 25% of the 80-mg group and 38% of the 40-mg group achieving an IGA score of 1 or 0.
Itching responded well to ASN002, but here, the 20-mg dose threw investigators a bit of a curve ball. Pruritus decreased most in the 80-mg group (about 70% by the end of the study). But at 3 weeks, patients taking 20 mg and 40 mg were experiencing the same 30% decrease in itch. By 4 weeks, however, the scores had separated, with the 40-mg group landing at about a 40% reduction, and the 20-mg group rebounding to about a 20% reduction.
“I would say that this first trial of ASN002 showed clear efficacy in patients with moderate to severe atopic dermatitis, with rapid improvement itch and a large proportion of patients reaching EASI-50 as early as 2 weeks,” Dr. Bissonnette said.
Asana will soon initiate a phase 2b study of ASN002 in moderate to severe atopic dermatitis patients. Clinical studies in other dermatologic and autoimmune indications are under consideration, according to the company website.
Dr. Bissonnette is the president of Innovaderm Research, which was paid to run the ASN002 study.
SOURCE: Bissonnette R et al. AAD 2018, Abstract 6777
REPORTING FROM AAD 2018
Key clinical point: ASN002 calmed itch, improved skin involvement in moderate to severe atopic dermatitis.
Major finding: After 29 days, 100% of those taking 80-mg doses of ASN002 daily achieved a 50% improvement in EASI.
Study details: The randomized dose-escalation phase 1b study comprised 36 patients with moderate to severe atopic dermatitis.
Disclosures: Asana BioSciences sponsored the study. Dr. Bissonnette is CEO of Innovaderm Research, Montreal, which conducted the trial.
Source: Bissonnette R et al. AAD 2018, Abstract 6777.
Upadacitinib calms itch, clears skin in moderate to severe atopic dermatitis
SAN DIEGO – Upadacitinib, a selective inhibitor of the Janus kinase 1 enzyme, affected up to 90% skin clearance in a phase 2 study in patients with moderate to severe atopic dermatitis (AD).
The molecule significantly outperformed placebo with all three of the doses tested, with patients experiencing improvement in itch and skin are involved in the first week of use. During the 16-week trial, there were none of the thromboembolic events that have proven a concern with other inhibitors of the Janus kinase family of enzymes, Emma Guttman, MD, PhD, said at the annual meeting of the American Academy of Dermatology.
The study enrolled adults (mean age, 40 years) with moderate to severe atopic dermatitis of about 30 years’ duration. Their mean Eczema Area and Severity Index (EASI) score at baseline was about 30, and mean Body Surface Area score ranged from 42-50. The mean pruritus numerical rating scale score was about 6.5.
After a month-long washout period that excluded all medications except a topical emollient, patients were randomized to placebo (40 patients) or to daily upadacitinib at 7.5-mg, 15-mg, or 30-mg doses, taken orally (42 in each group). The 16-week placebo-controlled period is being followed by a 72-week blinded extension study in which the placebo patients will be switched to upadacitinib 30 mg, and half of each upadacitinib group will be switched to placebo. Dr. Guttman reported only the 16-week results.
The study’s primary endpoint was the mean percent EASI improvement from baseline. Dr. Guttman reported several of the key secondary endpoints as well.
On the primary endpoint, all three doses of upadacitinib separated from placebo quickly and dramatically. Patients began to see some skin clearance after 1 week; by 2 weeks, the 7.5-mg group had achieved a 39% improvement and the 15- and 30-mg groups, 56% and 59% improvement, respectively.
Efficacy in the 7.5-mg group peaked at a 50% improvement by week 4, and then trailed off somewhat, with a mean 39% improvement by week 16.
Efficacy in the two higher dose groups also peaked around 4 weeks, with a 66% improvement in the 15-mg group and a 78% improvement in the 30-mg group. There was some tailing off of effect in each of these groups as well. By 16 weeks, the mean EASI improvement was 61.7% in the 15-mg group and 74.4% in the 30-mg group.
A good number of patients in each dosing group even achieved 90% skin clearance, Dr. Guttman noted.
“We generally say that we like to see an EASI 50, but now we are talking about EASI 75 and even 90. More than 60% on the highest dose achieved an EASI 75 and 60% an EASI 90. Even the 15-mg group achieved a nice EASI 90 response, at around 26%.”
Itching also responded well to upadacitinib, Dr. Guttman said. Within 1 week, all three active groups had separated significantly from the placebo group. By 2 weeks, the 7.5-mg group had a mean 29% improvement on the pruritus numerical rating scale. The improvement was 46% in the 15-mg group and 57.6% in the 30-mg group. By 16 weeks, the improvements were 39.6%, 48%, and 68.9%, respectively, compared with 9.7% among those on placebo.
The most common treatment-emergent adverse event was upper respiratory infection, which Dr. Guttman noted has been seen with JAK inhibitors. This occurred in 10% of those taking placebo and in 16.7% of the 7.5-mg group and 11.9% of both the 15-mg and 30-mg groups. A few patients experienced exacerbation of their AD on the medication (16.7%, 7% and 11.9% of the active groups, compared with 7.5% of those on placebo). New acne developed in 2.5% of placebo patients and in 9.5%, 4.8%, and 14.3% of those taking upadacitinib. The acne was on the body, considered mild, and resolved, Dr. Guttman said.
Two patients taking 7.5 mg and one taking 15 mg developed a serious infection, although she did not elaborate on the illnesses. Two taking 15 mg developed a liver disorder. There were four cases of neutropenia and one lymphopenia, all among the active groups. Creatine phosphokinase elevations occurred in one taking placebo and seven taking the study drug.
There were no pulmonary or deep vein thromboses; no opportunistic infections or malignancies; and no cases of herpes zoster, tuberculosis, or renal dysfunction. There were no deaths during the trial.
Phase 3 studies of upadacitinib in patients with rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease are underway, according to AbbVie.
AbbVie sponsored the AD study. Dr. Guttman is a consultant for the company.
SOURCE: Guttman E et al. AAD late-breaking clinical trials, Abstract 6533
SAN DIEGO – Upadacitinib, a selective inhibitor of the Janus kinase 1 enzyme, affected up to 90% skin clearance in a phase 2 study in patients with moderate to severe atopic dermatitis (AD).
The molecule significantly outperformed placebo with all three of the doses tested, with patients experiencing improvement in itch and skin are involved in the first week of use. During the 16-week trial, there were none of the thromboembolic events that have proven a concern with other inhibitors of the Janus kinase family of enzymes, Emma Guttman, MD, PhD, said at the annual meeting of the American Academy of Dermatology.
The study enrolled adults (mean age, 40 years) with moderate to severe atopic dermatitis of about 30 years’ duration. Their mean Eczema Area and Severity Index (EASI) score at baseline was about 30, and mean Body Surface Area score ranged from 42-50. The mean pruritus numerical rating scale score was about 6.5.
After a month-long washout period that excluded all medications except a topical emollient, patients were randomized to placebo (40 patients) or to daily upadacitinib at 7.5-mg, 15-mg, or 30-mg doses, taken orally (42 in each group). The 16-week placebo-controlled period is being followed by a 72-week blinded extension study in which the placebo patients will be switched to upadacitinib 30 mg, and half of each upadacitinib group will be switched to placebo. Dr. Guttman reported only the 16-week results.
The study’s primary endpoint was the mean percent EASI improvement from baseline. Dr. Guttman reported several of the key secondary endpoints as well.
On the primary endpoint, all three doses of upadacitinib separated from placebo quickly and dramatically. Patients began to see some skin clearance after 1 week; by 2 weeks, the 7.5-mg group had achieved a 39% improvement and the 15- and 30-mg groups, 56% and 59% improvement, respectively.
Efficacy in the 7.5-mg group peaked at a 50% improvement by week 4, and then trailed off somewhat, with a mean 39% improvement by week 16.
Efficacy in the two higher dose groups also peaked around 4 weeks, with a 66% improvement in the 15-mg group and a 78% improvement in the 30-mg group. There was some tailing off of effect in each of these groups as well. By 16 weeks, the mean EASI improvement was 61.7% in the 15-mg group and 74.4% in the 30-mg group.
A good number of patients in each dosing group even achieved 90% skin clearance, Dr. Guttman noted.
“We generally say that we like to see an EASI 50, but now we are talking about EASI 75 and even 90. More than 60% on the highest dose achieved an EASI 75 and 60% an EASI 90. Even the 15-mg group achieved a nice EASI 90 response, at around 26%.”
Itching also responded well to upadacitinib, Dr. Guttman said. Within 1 week, all three active groups had separated significantly from the placebo group. By 2 weeks, the 7.5-mg group had a mean 29% improvement on the pruritus numerical rating scale. The improvement was 46% in the 15-mg group and 57.6% in the 30-mg group. By 16 weeks, the improvements were 39.6%, 48%, and 68.9%, respectively, compared with 9.7% among those on placebo.
The most common treatment-emergent adverse event was upper respiratory infection, which Dr. Guttman noted has been seen with JAK inhibitors. This occurred in 10% of those taking placebo and in 16.7% of the 7.5-mg group and 11.9% of both the 15-mg and 30-mg groups. A few patients experienced exacerbation of their AD on the medication (16.7%, 7% and 11.9% of the active groups, compared with 7.5% of those on placebo). New acne developed in 2.5% of placebo patients and in 9.5%, 4.8%, and 14.3% of those taking upadacitinib. The acne was on the body, considered mild, and resolved, Dr. Guttman said.
Two patients taking 7.5 mg and one taking 15 mg developed a serious infection, although she did not elaborate on the illnesses. Two taking 15 mg developed a liver disorder. There were four cases of neutropenia and one lymphopenia, all among the active groups. Creatine phosphokinase elevations occurred in one taking placebo and seven taking the study drug.
There were no pulmonary or deep vein thromboses; no opportunistic infections or malignancies; and no cases of herpes zoster, tuberculosis, or renal dysfunction. There were no deaths during the trial.
Phase 3 studies of upadacitinib in patients with rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease are underway, according to AbbVie.
AbbVie sponsored the AD study. Dr. Guttman is a consultant for the company.
SOURCE: Guttman E et al. AAD late-breaking clinical trials, Abstract 6533
SAN DIEGO – Upadacitinib, a selective inhibitor of the Janus kinase 1 enzyme, affected up to 90% skin clearance in a phase 2 study in patients with moderate to severe atopic dermatitis (AD).
The molecule significantly outperformed placebo with all three of the doses tested, with patients experiencing improvement in itch and skin are involved in the first week of use. During the 16-week trial, there were none of the thromboembolic events that have proven a concern with other inhibitors of the Janus kinase family of enzymes, Emma Guttman, MD, PhD, said at the annual meeting of the American Academy of Dermatology.
The study enrolled adults (mean age, 40 years) with moderate to severe atopic dermatitis of about 30 years’ duration. Their mean Eczema Area and Severity Index (EASI) score at baseline was about 30, and mean Body Surface Area score ranged from 42-50. The mean pruritus numerical rating scale score was about 6.5.
After a month-long washout period that excluded all medications except a topical emollient, patients were randomized to placebo (40 patients) or to daily upadacitinib at 7.5-mg, 15-mg, or 30-mg doses, taken orally (42 in each group). The 16-week placebo-controlled period is being followed by a 72-week blinded extension study in which the placebo patients will be switched to upadacitinib 30 mg, and half of each upadacitinib group will be switched to placebo. Dr. Guttman reported only the 16-week results.
The study’s primary endpoint was the mean percent EASI improvement from baseline. Dr. Guttman reported several of the key secondary endpoints as well.
On the primary endpoint, all three doses of upadacitinib separated from placebo quickly and dramatically. Patients began to see some skin clearance after 1 week; by 2 weeks, the 7.5-mg group had achieved a 39% improvement and the 15- and 30-mg groups, 56% and 59% improvement, respectively.
Efficacy in the 7.5-mg group peaked at a 50% improvement by week 4, and then trailed off somewhat, with a mean 39% improvement by week 16.
Efficacy in the two higher dose groups also peaked around 4 weeks, with a 66% improvement in the 15-mg group and a 78% improvement in the 30-mg group. There was some tailing off of effect in each of these groups as well. By 16 weeks, the mean EASI improvement was 61.7% in the 15-mg group and 74.4% in the 30-mg group.
A good number of patients in each dosing group even achieved 90% skin clearance, Dr. Guttman noted.
“We generally say that we like to see an EASI 50, but now we are talking about EASI 75 and even 90. More than 60% on the highest dose achieved an EASI 75 and 60% an EASI 90. Even the 15-mg group achieved a nice EASI 90 response, at around 26%.”
Itching also responded well to upadacitinib, Dr. Guttman said. Within 1 week, all three active groups had separated significantly from the placebo group. By 2 weeks, the 7.5-mg group had a mean 29% improvement on the pruritus numerical rating scale. The improvement was 46% in the 15-mg group and 57.6% in the 30-mg group. By 16 weeks, the improvements were 39.6%, 48%, and 68.9%, respectively, compared with 9.7% among those on placebo.
The most common treatment-emergent adverse event was upper respiratory infection, which Dr. Guttman noted has been seen with JAK inhibitors. This occurred in 10% of those taking placebo and in 16.7% of the 7.5-mg group and 11.9% of both the 15-mg and 30-mg groups. A few patients experienced exacerbation of their AD on the medication (16.7%, 7% and 11.9% of the active groups, compared with 7.5% of those on placebo). New acne developed in 2.5% of placebo patients and in 9.5%, 4.8%, and 14.3% of those taking upadacitinib. The acne was on the body, considered mild, and resolved, Dr. Guttman said.
Two patients taking 7.5 mg and one taking 15 mg developed a serious infection, although she did not elaborate on the illnesses. Two taking 15 mg developed a liver disorder. There were four cases of neutropenia and one lymphopenia, all among the active groups. Creatine phosphokinase elevations occurred in one taking placebo and seven taking the study drug.
There were no pulmonary or deep vein thromboses; no opportunistic infections or malignancies; and no cases of herpes zoster, tuberculosis, or renal dysfunction. There were no deaths during the trial.
Phase 3 studies of upadacitinib in patients with rheumatoid arthritis, psoriatic arthritis, and Crohn’s disease are underway, according to AbbVie.
AbbVie sponsored the AD study. Dr. Guttman is a consultant for the company.
SOURCE: Guttman E et al. AAD late-breaking clinical trials, Abstract 6533
REPORTING FROM AAD 2018
Key clinical point: Upadacitinib had significant effects on reducing itch and clearing skin in patients with moderate to severe atopic dermatitis
Major finding: By 16 weeks, the mean EASI improvement was 61.7% in the 15-mg group and 74.4% in the 30-mg group.
Study details: In the dose-ranging, phase 2b randomized, placebo-controlled study, 126 patients with moderate to severe AD were treated with one of 3 upadacitinib doses, and 40 received placebo for 16 weeks.
Disclosures: AbbVie sponsored the study. Dr. Guttman is a consultant for the company.
Source: Guttman E et al. AAD late-breaking clinical trials, Abstract 6533
Risankizumab outpaced ustekinumab for complete clearance of plaque psoriasis
SAN DIEGO – Risankizumab outperformed ustekinumab in two phase 3 trials investigating the IL-23 blocker for moderate to severe plaque psoriasis.
In two year-long studies, 56% and 59% of those taking risankizumab and 21% and 30% of those taking ustekinumab achieved completely clear skin, Kenneth B. Gordon, MD, said at the annual meeting of the American Academy of Dermatology.
“One of the things we are striving for now is complete skin clearance,” said Dr. Gordon, chair of the dermatology department the Medical College of Wisconsin, Milwaukee. “In the past, people have said that it wasn’t important to reach that, yet here we are, getting more than 50% of patients to that point.”
Risankizumab is an investigational monoclonal antibody that selectively blocks IL-23, a key inflammatory protein. The drug is also in phase 3 trials for Crohn's disease, and being investigated for psoriatic arthritis. AbbVie, which is developing risankizumab, plans future trials for treating ulcerative colitis.
Dr. Gordon reported the results of UltIMMa-1 and UltIMMa-2, identical three-armed studies that randomized a total of 797 patients with moderate to severe plaque psoriasis to risankizumab 150 mg, ustekinumab 45 mg or 90 mg (based on weight), or to a crossover group that took placebo for the first 16 weeks of the study and then were switched to risankizumab 150 mg for the remainder of the study. Study drugs were delivered at weeks 0, 4, 16, 28, and 40.
The coprimary endpoints were at least a 90% improvement in the Psoriasis Area Severity Index score (PASI 90) at week 16 and a score of 0 or 1 on the Static Physicians’ Assessment scale (sPGA 0/1) at week 16, compared with placebo. Key secondary endpoints compared risankizumab with ustekinumab: PASI 90, sPGA score of clear (sPGA 0), sPGA 0/1, and Dermatology Quality of Life (DLQI) score of 0/1 at week 16, and PASI 90, PASI 100 and sPGA 0 at week 52.
In both trials, patients were 48 years old on average; about 20% had severe plaque psoriasis. The mean PASI score was about 20 at trial entry. Prior therapy included biologics in 30%-43%, depending on the trial, and TNF-alpha inhibitors in about 25%.
Patient retention in the study was good, Dr. Gordon noted, with 95% of risankizumab patients still taking the drug at 52 weeks. Patients also stayed on ustekinumab, with 94% of UltIMMa-1 patients and 91% of UltIMMa-2 patients still taking the drug at 52 weeks.
At week 16, risankizumab was clearly superior to placebo in both endpoints. In both studies, 75% of actively treated patients achieved PASI 90, compared to 5% of those taking placebo. In UltIMMa-1, a clear or almost clear sPGA was seen in 88% of risankizumab patients as compared to 8% of those taking placebo. In UltIMMa-2, these numbers were 84% and 5%, respectively.
In the secondary comparison of the two active drugs, risankizumab significantly outperformed ustekinumab on PASI90 at 16 weeks in UltIMMa-1 (75% vs. 42%) and in UltIMMa-2 (75% vs. 47%). The PASI90 outcomes similarly favored risankizumab at 52 weeks in UltIMMa-1 (82% vs. 44%) and in UltIMMa-2 (81% vs. 50%).
As compared with ustekinumab, risankizumab aced the secondary endpoint of complete skin clearance in UltIMMa-1 and (36% vs. 12%) and UltIMMa-2 (51% vs. 24%). The results similarly favored risankizumab at 52 weeks in both trials (56% vs. 21% and 59% vs. 30%).
Another secondary endpoint looked at how the crossover group fared. At week 51, the PASI90 for this group was 78% in UltIMMa-1 and 85% in UltIMMa-2; the PASI100 at 52 weeks for these patients was 55% and 67%.
A responder time curve demonstrated just how quickly the crossover patients made up for lost time after switching to risankizumab. Although these patients made no progress toward disease clearance during their placebo period, they quickly caught up with the primary risankizumab group. At 16 weeks, 5% in this group had a PASI 90; by week 28, 51% did; and by week 52, PASI 90 topped out at 78%.
“The time course seen in this trial is very important,” Dr. Gordon said. “By 8 weeks, almost 44% [of the primary risankizumab group] was already at PASI90. They reached an extremely high level of response that was very consistent over 1 year. In the ustekinumab group, we saw some saw-toothing of response, indicating that people were losing effectiveness at the end of the dosing period. With risankizumab, we did not see that, indicating that the once every 12 weeks dosing period is effective.”
The DLQI 0/1 outcome occurred at 16 and 52 weeks in significantly more patients taking risankizumab in both studies. By week 52 in UltIMMa-1, 75% of patients on risankizumab had achieved a DLQ1 0/1, compared with 47% of the ustekinumab group. In UltIMMa-2, these numbers were 71% and 44%, with the crossover group posting scores similar to the primary risankizumab group in both studies (62% and 68%).
Risankizumab proved safe and well tolerated, Dr. Gordon said. Less than 1% of patients discontinued the medication due to an adverse event. In both the UltIMMa-1 and UltIMMa-2 trials, the most frequently reported treatment-emergent adverse event in the risankizumab groups was upper respiratory tract infection. In UltIMMa-1, one patient receiving risankizumab presented with latent tuberculosis and was treated with rifampicin. There were no new cases of tuberculosis.
The serious adverse event rate hovered between 2%-3% in both trials. The rate of serious infection was 1%. The rate of malignancy was 0.3%, but fell to 0 when nonmelanoma skin cancer was excluded. There were no major cardiovascular events.
"Not only do these data show significant rates of clear skin, but because we know the burden of psoriasis extends beyond the skin, we are encouraged by the patient-reported improvement in quality of life after one year of treatment," he said. "Given the significant impact of psoriasis, it is important to continue to investigate additional treatment options."
AbbVie sponsored the trials. Dr. Gordon is a consultant for the company.
SOURCE: Gordon et al. AAD, Abstract 6495
SAN DIEGO – Risankizumab outperformed ustekinumab in two phase 3 trials investigating the IL-23 blocker for moderate to severe plaque psoriasis.
In two year-long studies, 56% and 59% of those taking risankizumab and 21% and 30% of those taking ustekinumab achieved completely clear skin, Kenneth B. Gordon, MD, said at the annual meeting of the American Academy of Dermatology.
“One of the things we are striving for now is complete skin clearance,” said Dr. Gordon, chair of the dermatology department the Medical College of Wisconsin, Milwaukee. “In the past, people have said that it wasn’t important to reach that, yet here we are, getting more than 50% of patients to that point.”
Risankizumab is an investigational monoclonal antibody that selectively blocks IL-23, a key inflammatory protein. The drug is also in phase 3 trials for Crohn's disease, and being investigated for psoriatic arthritis. AbbVie, which is developing risankizumab, plans future trials for treating ulcerative colitis.
Dr. Gordon reported the results of UltIMMa-1 and UltIMMa-2, identical three-armed studies that randomized a total of 797 patients with moderate to severe plaque psoriasis to risankizumab 150 mg, ustekinumab 45 mg or 90 mg (based on weight), or to a crossover group that took placebo for the first 16 weeks of the study and then were switched to risankizumab 150 mg for the remainder of the study. Study drugs were delivered at weeks 0, 4, 16, 28, and 40.
The coprimary endpoints were at least a 90% improvement in the Psoriasis Area Severity Index score (PASI 90) at week 16 and a score of 0 or 1 on the Static Physicians’ Assessment scale (sPGA 0/1) at week 16, compared with placebo. Key secondary endpoints compared risankizumab with ustekinumab: PASI 90, sPGA score of clear (sPGA 0), sPGA 0/1, and Dermatology Quality of Life (DLQI) score of 0/1 at week 16, and PASI 90, PASI 100 and sPGA 0 at week 52.
In both trials, patients were 48 years old on average; about 20% had severe plaque psoriasis. The mean PASI score was about 20 at trial entry. Prior therapy included biologics in 30%-43%, depending on the trial, and TNF-alpha inhibitors in about 25%.
Patient retention in the study was good, Dr. Gordon noted, with 95% of risankizumab patients still taking the drug at 52 weeks. Patients also stayed on ustekinumab, with 94% of UltIMMa-1 patients and 91% of UltIMMa-2 patients still taking the drug at 52 weeks.
At week 16, risankizumab was clearly superior to placebo in both endpoints. In both studies, 75% of actively treated patients achieved PASI 90, compared to 5% of those taking placebo. In UltIMMa-1, a clear or almost clear sPGA was seen in 88% of risankizumab patients as compared to 8% of those taking placebo. In UltIMMa-2, these numbers were 84% and 5%, respectively.
In the secondary comparison of the two active drugs, risankizumab significantly outperformed ustekinumab on PASI90 at 16 weeks in UltIMMa-1 (75% vs. 42%) and in UltIMMa-2 (75% vs. 47%). The PASI90 outcomes similarly favored risankizumab at 52 weeks in UltIMMa-1 (82% vs. 44%) and in UltIMMa-2 (81% vs. 50%).
As compared with ustekinumab, risankizumab aced the secondary endpoint of complete skin clearance in UltIMMa-1 and (36% vs. 12%) and UltIMMa-2 (51% vs. 24%). The results similarly favored risankizumab at 52 weeks in both trials (56% vs. 21% and 59% vs. 30%).
Another secondary endpoint looked at how the crossover group fared. At week 51, the PASI90 for this group was 78% in UltIMMa-1 and 85% in UltIMMa-2; the PASI100 at 52 weeks for these patients was 55% and 67%.
A responder time curve demonstrated just how quickly the crossover patients made up for lost time after switching to risankizumab. Although these patients made no progress toward disease clearance during their placebo period, they quickly caught up with the primary risankizumab group. At 16 weeks, 5% in this group had a PASI 90; by week 28, 51% did; and by week 52, PASI 90 topped out at 78%.
“The time course seen in this trial is very important,” Dr. Gordon said. “By 8 weeks, almost 44% [of the primary risankizumab group] was already at PASI90. They reached an extremely high level of response that was very consistent over 1 year. In the ustekinumab group, we saw some saw-toothing of response, indicating that people were losing effectiveness at the end of the dosing period. With risankizumab, we did not see that, indicating that the once every 12 weeks dosing period is effective.”
The DLQI 0/1 outcome occurred at 16 and 52 weeks in significantly more patients taking risankizumab in both studies. By week 52 in UltIMMa-1, 75% of patients on risankizumab had achieved a DLQ1 0/1, compared with 47% of the ustekinumab group. In UltIMMa-2, these numbers were 71% and 44%, with the crossover group posting scores similar to the primary risankizumab group in both studies (62% and 68%).
Risankizumab proved safe and well tolerated, Dr. Gordon said. Less than 1% of patients discontinued the medication due to an adverse event. In both the UltIMMa-1 and UltIMMa-2 trials, the most frequently reported treatment-emergent adverse event in the risankizumab groups was upper respiratory tract infection. In UltIMMa-1, one patient receiving risankizumab presented with latent tuberculosis and was treated with rifampicin. There were no new cases of tuberculosis.
The serious adverse event rate hovered between 2%-3% in both trials. The rate of serious infection was 1%. The rate of malignancy was 0.3%, but fell to 0 when nonmelanoma skin cancer was excluded. There were no major cardiovascular events.
"Not only do these data show significant rates of clear skin, but because we know the burden of psoriasis extends beyond the skin, we are encouraged by the patient-reported improvement in quality of life after one year of treatment," he said. "Given the significant impact of psoriasis, it is important to continue to investigate additional treatment options."
AbbVie sponsored the trials. Dr. Gordon is a consultant for the company.
SOURCE: Gordon et al. AAD, Abstract 6495
SAN DIEGO – Risankizumab outperformed ustekinumab in two phase 3 trials investigating the IL-23 blocker for moderate to severe plaque psoriasis.
In two year-long studies, 56% and 59% of those taking risankizumab and 21% and 30% of those taking ustekinumab achieved completely clear skin, Kenneth B. Gordon, MD, said at the annual meeting of the American Academy of Dermatology.
“One of the things we are striving for now is complete skin clearance,” said Dr. Gordon, chair of the dermatology department the Medical College of Wisconsin, Milwaukee. “In the past, people have said that it wasn’t important to reach that, yet here we are, getting more than 50% of patients to that point.”
Risankizumab is an investigational monoclonal antibody that selectively blocks IL-23, a key inflammatory protein. The drug is also in phase 3 trials for Crohn's disease, and being investigated for psoriatic arthritis. AbbVie, which is developing risankizumab, plans future trials for treating ulcerative colitis.
Dr. Gordon reported the results of UltIMMa-1 and UltIMMa-2, identical three-armed studies that randomized a total of 797 patients with moderate to severe plaque psoriasis to risankizumab 150 mg, ustekinumab 45 mg or 90 mg (based on weight), or to a crossover group that took placebo for the first 16 weeks of the study and then were switched to risankizumab 150 mg for the remainder of the study. Study drugs were delivered at weeks 0, 4, 16, 28, and 40.
The coprimary endpoints were at least a 90% improvement in the Psoriasis Area Severity Index score (PASI 90) at week 16 and a score of 0 or 1 on the Static Physicians’ Assessment scale (sPGA 0/1) at week 16, compared with placebo. Key secondary endpoints compared risankizumab with ustekinumab: PASI 90, sPGA score of clear (sPGA 0), sPGA 0/1, and Dermatology Quality of Life (DLQI) score of 0/1 at week 16, and PASI 90, PASI 100 and sPGA 0 at week 52.
In both trials, patients were 48 years old on average; about 20% had severe plaque psoriasis. The mean PASI score was about 20 at trial entry. Prior therapy included biologics in 30%-43%, depending on the trial, and TNF-alpha inhibitors in about 25%.
Patient retention in the study was good, Dr. Gordon noted, with 95% of risankizumab patients still taking the drug at 52 weeks. Patients also stayed on ustekinumab, with 94% of UltIMMa-1 patients and 91% of UltIMMa-2 patients still taking the drug at 52 weeks.
At week 16, risankizumab was clearly superior to placebo in both endpoints. In both studies, 75% of actively treated patients achieved PASI 90, compared to 5% of those taking placebo. In UltIMMa-1, a clear or almost clear sPGA was seen in 88% of risankizumab patients as compared to 8% of those taking placebo. In UltIMMa-2, these numbers were 84% and 5%, respectively.
In the secondary comparison of the two active drugs, risankizumab significantly outperformed ustekinumab on PASI90 at 16 weeks in UltIMMa-1 (75% vs. 42%) and in UltIMMa-2 (75% vs. 47%). The PASI90 outcomes similarly favored risankizumab at 52 weeks in UltIMMa-1 (82% vs. 44%) and in UltIMMa-2 (81% vs. 50%).
As compared with ustekinumab, risankizumab aced the secondary endpoint of complete skin clearance in UltIMMa-1 and (36% vs. 12%) and UltIMMa-2 (51% vs. 24%). The results similarly favored risankizumab at 52 weeks in both trials (56% vs. 21% and 59% vs. 30%).
Another secondary endpoint looked at how the crossover group fared. At week 51, the PASI90 for this group was 78% in UltIMMa-1 and 85% in UltIMMa-2; the PASI100 at 52 weeks for these patients was 55% and 67%.
A responder time curve demonstrated just how quickly the crossover patients made up for lost time after switching to risankizumab. Although these patients made no progress toward disease clearance during their placebo period, they quickly caught up with the primary risankizumab group. At 16 weeks, 5% in this group had a PASI 90; by week 28, 51% did; and by week 52, PASI 90 topped out at 78%.
“The time course seen in this trial is very important,” Dr. Gordon said. “By 8 weeks, almost 44% [of the primary risankizumab group] was already at PASI90. They reached an extremely high level of response that was very consistent over 1 year. In the ustekinumab group, we saw some saw-toothing of response, indicating that people were losing effectiveness at the end of the dosing period. With risankizumab, we did not see that, indicating that the once every 12 weeks dosing period is effective.”
The DLQI 0/1 outcome occurred at 16 and 52 weeks in significantly more patients taking risankizumab in both studies. By week 52 in UltIMMa-1, 75% of patients on risankizumab had achieved a DLQ1 0/1, compared with 47% of the ustekinumab group. In UltIMMa-2, these numbers were 71% and 44%, with the crossover group posting scores similar to the primary risankizumab group in both studies (62% and 68%).
Risankizumab proved safe and well tolerated, Dr. Gordon said. Less than 1% of patients discontinued the medication due to an adverse event. In both the UltIMMa-1 and UltIMMa-2 trials, the most frequently reported treatment-emergent adverse event in the risankizumab groups was upper respiratory tract infection. In UltIMMa-1, one patient receiving risankizumab presented with latent tuberculosis and was treated with rifampicin. There were no new cases of tuberculosis.
The serious adverse event rate hovered between 2%-3% in both trials. The rate of serious infection was 1%. The rate of malignancy was 0.3%, but fell to 0 when nonmelanoma skin cancer was excluded. There were no major cardiovascular events.
"Not only do these data show significant rates of clear skin, but because we know the burden of psoriasis extends beyond the skin, we are encouraged by the patient-reported improvement in quality of life after one year of treatment," he said. "Given the significant impact of psoriasis, it is important to continue to investigate additional treatment options."
AbbVie sponsored the trials. Dr. Gordon is a consultant for the company.
SOURCE: Gordon et al. AAD, Abstract 6495
REPORTING FROM AAD 18
Key clinical point: Risankizumab outperformed placebo and the active comparator ustekinumab.
Major finding: In the two studies, 56% and 59% of those taking risankizumab had clear skin as compared to 21% and 30% of those taking ustekinumab.
Study details: The twin placebo-crossover active comparator trials randomized 797 patients.
Disclosures: AbbVie sponsored the studies. Dr. Gordon is a consultant for the company.
Source: Gordon et al. AAD abstract 6495