Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Supplementing breastfed infants with bifidobacteria promotes development of a well-regulated immune system, theoretically reducing risk of immune-mediated conditions like allergies and asthma, according to investigators.

These findings support the importance of early gut colonization with beneficial microbes, an event that may affect the immune system throughout life, reported lead author Bethany M. Henrick, PhD, director of immunology and diagnostics at Evolve Biosystems, Davis, Calif., and adjunct assistant professor at the University of Nebraska, Lincoln, and colleagues.

“Dysbiosis of the infant gut microbiome is common in modern societies and a likely contributing factor to the increased incidences of immune-mediated disorders,” the investigators wrote in Cell. “Therefore, there is great interest in identifying microbial factors that can support healthier immune system imprinting and hopefully prevent cases of allergy, autoimmunity, and possibly other conditions involving the immune system.”

Prevailing theory suggests that the rising incidence of neonatal intestinal dysbiosis – which is typical in developed countries – may be caused by a variety of factors, including cesarean sections; modern hygiene practices; antibiotics, antiseptics, and other medications; diets high in fat and sugar; and infant formula.

According to Dr. Henrick and colleagues, a healthy gut microbiome plays the greatest role in immunological development during the first 3 months post partum; specifically, a lack of bifidobacteria during this time has been linked with increased risks of autoimmunity and enteric inflammation, although underlying immune mechanisms remain unclear.

Bifidobacteria also exemplify the symbiotic relationship between mothers, babies, and beneficial microbes. The investigators pointed out that breast milk contains human milk oligosaccharides (HMOs), which humans cannot digest, but are an excellent source of energy for bifidobacteria and other beneficial microbes, giving them a “selective nutritional advantage.”

Bifidobacteria should therefore be common residents within the infant gut, but this is often not now the case, leading Dr. Henrick and colleagues to zero in on the microbe, in hopes of determining the exactly how beneficial bacteria shape immune development.

It is only recently that the necessary knowledge and techniques to perform studies like this one have become available, the investigators wrote, noting a better understanding of cell-regulatory relationships, advances in immune profiling at the systems level, and new technology that allows for profiling small-volume samples from infants.

The present study involved a series of observational experiments and a small interventional trial.

First, the investigators conducted a wide array of blood- and fecal-based longitudinal analyses from 208 infants in Sweden to characterize immune cell expansion and microbiome colonization of the gut, with a focus on bifidobacteria.

Their results showed that infants lacking bifidobacteria, and HMO-utilization genes (which are expressed by bifidobacteria and other beneficial microbes), had higher levels of systemic inflammation, including increased T helper 2 (Th2) and Th17 responses.

“Infants not colonized by Bifidobacteriaceae or in cases where these microbes fail to expand during the first months of life there is evidence of systemic and intestinal inflammation, increased frequencies of activated immune cells, and reduced levels of regulatory cells indicative of systemic immune dysregulation,” the investigators wrote.

The interventional part of the study involved 60 breastfed infants in California. Twenty-nine of the newborns were given 1.8 x 10¹⁰ colony-forming units (CFUs) of B. longum subsp. infantis EVC001 daily from postnatal day 7 to day 28, while the remaining 31 infants were given no supplementation.

Fecal samples were collected on day 6 and day 60. At day 60, supplemented infants had high levels of HMO-utilization genes, plus significantly greater alpha diversity (P = .0001; Wilcoxon), compared with controls. Infants receiving EVC001 also had less inflammatory fecal cytokines, suggesting that microbes expressing HMO-utilization genes cause a shift away from proinflammatory Th2 and Th17 responses, and toward Th1.

“It is not the simple presence of bifidobacteria that is responsible for the immune effects but the metabolic partnership between the bacteria and HMOs,” the investigators noted.

According to principal investigator Petter Brodin, MD, PhD, professor of pediatric immunology at Karolinska Institutet, Solna, Sweden, the findings deserve further investigation.

“Our data indicate that substitution with beneficial microbes efficiently metabolizing HMOs could open a way to prevent cases of immune-mediated diseases, but larger, randomized trials aimed at this will be required to determine this potential,” Dr. Brodin said in an interview.

Carolynn Dude, MD, PhD, assistant professor in the division of maternal-fetal medicine at Emory University, Atlanta, agreed that more work is needed.

“While this study provides some insight into the mechanisms that may set up a newborn for poor health outcomes later in life, the data is still very limited, and more long-term follow-up on these infants is needed before recommending any sort of bacterial supplementation to a newborn,” Dr. Dude said in an interview.

Dr. Brodin and colleagues are planning an array of related studies, including larger clinical trials; further investigations into mechanisms of action; comparisons between the present cohort and infants in Kenya, where immune-mediated diseases are rare; and evaluations of vaccine responses and infectious disease susceptibility.

The study was supported by the European Research Council, the Swedish Research Council, the Marianne & Marcus Wallenberg Foundation, and others. The investigators disclosed relationships with Cytodelics, Scailyte, Kancera, and others. Dr. Dude reported no relevant conflicts of interest.

Background: Recent studies have shown that the level of proteinuria increases after AKI. It is not yet shown if this increases risk of kidney disease progression.

Episodes of AKI were also associated with progression, but this is severely attenuated once adjusted for ACR, eGFR, and traditional CKD risk factors. This suggests more routine quantification of proteinuria after AKI for better risk stratification.

Bottom line: Posthospitalization ACR predicts progression of kidney disease.

Citation: Hsu CY et al. Post–acute kidney injury proteinuria and subsequent kidney disease progression. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6390.

Dr. Ho is a hospitalist and associate professor of medicine at University of Texas Health, San Antonio.

Background: Recent studies have shown that the level of proteinuria increases after AKI. It is not yet shown if this increases risk of kidney disease progression.

Episodes of AKI were also associated with progression, but this is severely attenuated once adjusted for ACR, eGFR, and traditional CKD risk factors. This suggests more routine quantification of proteinuria after AKI for better risk stratification.

Bottom line: Posthospitalization ACR predicts progression of kidney disease.

Citation: Hsu CY et al. Post–acute kidney injury proteinuria and subsequent kidney disease progression. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6390.

Dr. Ho is a hospitalist and associate professor of medicine at University of Texas Health, San Antonio.

Background: Recent studies have shown that the level of proteinuria increases after AKI. It is not yet shown if this increases risk of kidney disease progression.

Episodes of AKI were also associated with progression, but this is severely attenuated once adjusted for ACR, eGFR, and traditional CKD risk factors. This suggests more routine quantification of proteinuria after AKI for better risk stratification.

Bottom line: Posthospitalization ACR predicts progression of kidney disease.

Citation: Hsu CY et al. Post–acute kidney injury proteinuria and subsequent kidney disease progression. JAMA Intern Med. 2020 Jan 27. doi: 10.1001/jamainternmed.2019.6390.

Dr. Ho is a hospitalist and associate professor of medicine at University of Texas Health, San Antonio.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

For adults with Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL), frontline therapy with the chemotherapy-free combination of ponatinib (Iclusig) and blinatumomab (Blincyto) shows promise as an alternative to early hematopoietic stem cell transplantation (HSCT), investigators in a single-arm phase 2 study reported.

In an interim analysis of the combination in patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase chronic myeloid leukemia (CML), 20 patients who received it as frontline therapy had a rate of complete responses (CR) or complete responses with partial recovery of blood counts (CRp) of 100% and a complete molecular remission (CMR) rate of 85%, reported Nicholas Short, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This translated into an estimated 2-year overall survival of 93%, with no patients undergoing transplant in first remission, and none having relapse at last follow-up,” he said in an oral abstract presented during the European Hematology Association annual congress.

Among patients with relapsed/refractory Ph+ALL, the CR/CRp rate was 89%, the CMR rate was 88%, and the estimated 2-year overall survival rate was 53%, he said.
 

Transplants on hold

“The big selling point is the ability to avoid stem cell transplant, which is not always the first thing you do in Ph-positive ALL, but it’s always on your mind,” said Gwen Nichols, MD, chief medical officer of the Leukemia and Lymphoma Society, who was not involved in the study.

“It looks, albeit with very limited follow-up, that patients haven’t relapsed yet such that transplant would be necessary. Anything we can do to avoid people having long-term complications that go along with an allogeneic transplant is a step in the right direction,” she said in an interview.
 

One combination, three cohorts

Ph+ALL comprises about 25% of all adult ALL. The standard of care in newly diagnosed patients is chemotherapy plus a tyrosine kinase inhibitor (TKI) targeted against the BCR-ABL transcript.

Ponatinib is a pan-BCR-ABL TKI that has been shown to have activity against ALL with T315I mutations, which are present in about 75% of the cases of relapsed disease, Dr. Short said.

Blinatumomab is a bi-specific T-cell engager (BiTe) that has been shown to be effective as monotherapy against relapsed/refractory Ph+ALL as monotherapy and in combination with dasatinib.

Dr. Short and colleagues enrolled patients with newly diagnosed or relapsed/refractory Ph+ALL or lymphoid accelerated or blast phase CML. Patients in the frontline cohort could have received one or two prior lines of chemotherapy with or without a TKI.

The patients all had Eastern Cooperative Oncology Group performance status of 0-2, and adequate liver function.

Patients with clinically significant cardiovascular disease or central nervous system disease pathology were excluded, except that patients with CNS leukemia could be enrolled.

The induction phase consisted of 30 mg ponatinib daily plus blinatumomab standard dosing on a 4-week-on, 2-week-off schedule. Patients in CMR, defined for frontline patients as undetectable BCR-ABL transcripts by polymerase chain reaction, then received up to four consolidation cycles of the regimen with ponatinib at a 15-mg dose, followed by 5 years of ponatinib 15-mg maintenance. All patients also received CNS prophylaxis with 12 cycles of intrathecal chemotherapy with alternating administration of methotrexate and cytarabine.

Of the 35 patients treated to date with the combination, 20 with Ph+ALL received it as frontline therapy and 10 received it for relapsed/refractory disease; 5 patients with CML in lymphoid blast phase also were treated.
 

High CMR, CR rates

As noted before, the CMR rate, the primary endpoint among patients with newly diagnosed Ph+ALL, was 85%, with a CR/CRp rate of 100%. Six of the patients in the frontline group and one in the salvage therapy group had CRs but were positive for minimal residual disease (MRD) at study outset.

The CR/CRp rate for the entire cohort of 28 patients (excluding those with a CR at start) was 96%, with only 1 patient who had relapsed/refractory disease not having a CR. This patient had received ponatinib in a prior salvage regimen.

The CMR rate among the entire cohort was 79%, with 85% of patients in the frontline ALL cohort having a CMR, 88% in the relapsed/refractory cohort, and 40% in the CML cohort. There were no early deaths among any patients.

“After one cycle of ponatinib plus blinatumomab, 84% of frontline patients had achieved at least a major molecular response, and 58% had achieved a CMR. Among those with relapsed/refractory Ph+ALL, 75% achieved CMR after one cycle of therapy,” Dr. Short said.

Of the 20 frontline patients in CR, one patient experienced visual changes and possible stroke that were considered possibly related to the study medication. This patient was taken off study. During a later maintenance regimen this patient developed a non-ST elevation myocardial infarction and died from postprocedural bleeding and hypovolemic shock following a cardiac catheterization procedure.

The remainder of patients in the frontline cohort had ongoing responses without the need for HSCT at last follow-up. There were no relapses, with a median duration of CR of 6 months,

Among the 10 with relapsed/refractory Ph+ALL, one did not have a response, and the remaining 9 had CR/CRps.

Of the latter groups, four went on to allogeneic HSCT and three were still alive; one patient who underwent a transplant experienced a relapse and died. One additional patient was alive with relapsed disease with T315I and E255V mutations at the time of relapse, one patient in CR who went off study due to insurance issues died from an unknown cause, and the three remaining patients had ongoing responses without transplant.

Among the five patients with CML in lymphoid blast phase, two had relapses, but both are still alive and currently in remission, and three have ongoing responses without transplant.

After a median follow-up of 12 months the 1-year event-free survival (EFS) rate for the entire 35-patient group was 76%, and the 2-year EFS was 70%.

The 1-year overall survival rate was 93%, and the 2-year OS rate was 80%.

Among patients in the frontline group, the 1-year and 2-year EFS and OS rates were all 93%.

For the relapsed/refractory cohort, the estimated 2-year EFS was 41% and OS was 53%. For the CML cohort, the 2-year EFS was 60%, with all patients still alive at last follow-up.

There were no grade 4 adverse events on study. Grade 3 adverse events considered at least possibly related to study treatment were elevated lipase, fever/febrile neutropenia, increased alanine aminotransferase, cerebrovascular ischemia, hypertension, pancreatitis, deep vein thrombosis, and encephalopathy. There were no cases of grade 3 cytokine release syndrome or tremor.

The study was sponsored by MD Anderson Cancer Center with collaboration from the National Cancer Institute, Amgen, and Takeda. Dr. Short has disclosed relationships with Amgen and Takeda. Dr. Nichols reported having no conflicts of interest.

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

[email protected]

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

[email protected]

Compared with their non-Black counterparts, Black patients with atopic dermatitis (AD) are significantly more likely to be younger, have lower household incomes, live in an urban setting, and use Medicaid or state assistance. They also have significantly poorer disease control and an increased rate of comorbid skin infections.

Those are among the key findings from a 25-question survey administered to members of the National Eczema Association.

“Black individuals with AD have a unique sociodemographic and disease profile,” lead study investigator Raj Chovatiya, MD, PhD, said during the Revolutionizing Atopic Dermatitis symposium. “Out-of-pocket expenses are just one component of the real-world burden faced by this population.”

According to Dr. Chovatiya, of the department of dermatology at Northwestern University, Chicago, the clinical phenotype and burden of AD can vary across racial and ethnic groups. Black race, for example, is associated with a higher prevalence of AD, a higher burden of moderate to severe disease, increased rates of allergic comorbidities, greater AD-related impact on health-related quality of life, and more treatment-resistant AD.

“These features can make long-term AD control very difficult,” he said. “Given the variable long-term efficacy and safety of current treatments, health care providers and patients often have to combine therapies, seek new treatments, and consider adjunctive approaches – all of which can contribute to increased costs.”

AD is also associated with a considerable financial burden, he continued, including direct health care costs, lost work productivity and out-of-pocket health care expenses. “Previous population-based studies suggest that there are multifactorial increases in overall out-of-pocket health expenses in AD,” Dr. Chovatiya said. “Black race in particular is thought to be associated with increased health care utilization in AD, but little is known about the out-of-pocket health care expenses.”

To characterize the categories and impact of out-of-pocket health care expenses associated with AD management among Black individuals, he and his colleagues administered a 25-question voluntary survey to 113,502 members of the NEA between Nov. 14 and Dec. 21, 2019. They included adults with a self-reported diagnosis of AD or children, teens, or young adults who had a caregiver responding for them. In all, 1,118 respondents met inclusion criteria. Questions included those about out-of-pocket expenses for AD over the past 30 days and over the past year, as well as the disease impact on household finances.

The cohort included 75% of individuals with AD; 25% were primary caregivers of children, teens, and young adults with AD. More than three-quarters of respondents (77%) were female, 73% were White, 11% were Black, 6% were Asian, and the remainder were from other ethnic backgrounds. More than half of respondents (58%) had employer-sponsored insurance coverage and the median annual household income was between $50,000 and $75,000.

Nearly three-quarters of respondents (74%) classified their AD severity as moderate or severe, and 63% reported minimally controlled or somewhat-controlled AD. Black respondents were significantly more likely to be younger, have lower household incomes, live in an urban setting, use Medicaid or state assistance, have poor disease control, and frequent skin infections (P ≤ .02). “A numerically higher proportion of Black respondents also had increased AD severity and reported the use of step-up therapy with systemic agents, prescription polypharmacy with three or more prescriptions, and a higher monthly out-of-pocket cost,” Dr. Chovatiya said.

Compared with their non-Black counterparts, Black survey respondents reported more out-of-pocket costs for prescription medications covered by insurance (74.2% vs. 63.6%, P = .04), prescription medications not covered by insurance (65.1% vs. 46.5%, P = .0004), ED visits (22.1% vs. 11.8%, P = .005), and outpatient laboratory testing (33.3% vs. 21.8%, P = .01). Black race was associated with increased household financial impact from out-of-pocket expenses (P = .0009), and predictors of financial impact included minimally controlled AD (adjusted odds ratio, 13.88; P = .02), comorbid anxiety and/or depression (aOR, 4.34; P = .01), systemic therapy (aOR, 4.34; P = .003), out-of-pocket costs that exceeded $200 per month (aOR, 14.28; P = .0003), and Medicaid insurance (aOR, 4.02; P = .03). Blacks with Medicaid had higher odds of harmful financial impact (aOR, 3.32; P = .0002) than respondents who were Black (aOR, 1.81; P = .04) or those with Medicaid alone (aOR, 1.39; P = .04).

“I looked at some of the findings from recent studies that have talked about this burden, including an increased prevalence among Black children, a higher likelihood of moderate to severe disease, higher rates of ED visits and hospitalizations, and increased prescription medications,” Dr. Chovatiya said.“Our findings reflect these racial and socioeconomic disparities and provide another piece of evidence for increased financial burden among Black individuals with AD and support the need for targeted strategies to address these inequities.”

The study received funding support from the NEA. Dr. Chovatiya disclosed that he is a consultant to, a speaker for, and/or a member of the advisory board for AbbVie, Incyte, and Regeneron/Sanofi-Genzyme.

[email protected]

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Pregnant women with a history of bariatric surgery have better cardiovascular adaptation to pregnancy compared with women who have similar early-pregnancy body mass index (BMI) but no history of weight loss surgery, new data suggest.

“Pregnant women who have had bariatric surgery demonstrate better cardiovascular adaptation through lower blood pressure, heart rate, and cardiac output, more favorable diastolic indices, and better systolic function,” reported Deesha Patel, MBBS MRCOG, specialist registrar, Chelsea and Westminster Hospital, London.

“Because the groups were matched for early pregnancy BMI, it’s unlikely that the results are due to weight loss alone but indicate that the metabolic alterations as a result of the surgery, via the enterocardiac axis, play an important role,” Dr. Patel continued.

The findings were presented at the Royal College of Obstetricians and Gynecologists 2021 Virtual World Congress.

Although obesity is known for its inflammatory and toxic effects on the cardiovascular system, it is not clear to what extent the various treatment options for obesity modify these risks in the long term, said Hutan Ashrafian, MD, clinical lecturer in surgery, Imperial College London.

“It is even less clear how anti-obesity interventions affect the cardiovascular system in pregnancy,” Dr. Ashrafian told this news organization.

“This very novel study in pregnant mothers having undergone the most successful and consistent intervention for severe obesity – bariatric or metabolic surgery – gives new clues as to the extent that bariatric procedures can alter cardiovascular risk in pregnant mothers,” continued Dr. Ashrafian, who was not involved in the study.

The results show how bariatric surgery has favorable effects on cardiac adaptation in pregnancy and in turn “might offer protection from pregnancy-related cardiovascular pathology such as preeclampsia,” explained Dr. Ashrafian. “This adds to the known effects of cardiovascular protection of bariatric surgery through the enterocardiac axis, which may explain a wider range of effects that can be translated within pregnancy and possibly following pregnancy in the postpartum era and beyond.”
 

A history of bariatric surgery versus no surgery

The prospective, longitudinal study compared 41 women who had a history of bariatric surgery with 41 women who had not undergone surgery. Patients’ characteristics were closely matched for age, BMI (34.5 kg/m2 and 34.3 kg/m2 in the surgery and bariatric surgery groups, respectively) and race. Hypertensive disorders in the post-surgery group were significantly less common compared with the no-surgery group (0% vs. 9.8%).

During the study, participants underwent cardiovascular assessment at 12-14 weeks, 20-24 weeks, and 30-32 weeks of gestation. The assessment included measurement of blood pressure and heart rate, transthoracic echocardiography, and 2D speckle tracking, performed offline to assess global longitudinal and circumferential strain.

Blood pressure readings across the three trimesters were consistently lower in the women who had undergone bariatric surgery compared with those in the no-surgery group, and all differences were statistically significant. Likewise, heart rate and cardiac output across the three trimesters were lower in the post-surgery cohort. However, there was no difference in stroke volume between the two groups.

As for diastolic function, there were more favorable indices in the post-surgery group with a higher E/A ratio, a marker of left ventricle filling (P < .001), and lower left atrial volume (P < .05), Dr. Patel reported.

With respect to systolic function, there was no difference in ejection fraction, but there was lower global longitudinal strain (P < .01) and global circumferential strain in the post-bariatric group (P = .02), suggesting better systolic function.

“Strain is a measure of differences in motion and velocity between regions of the myocardium through the cardiac cycle and can detect subclinical changes when ejection fraction is normal,” she added.

“This is a fascinating piece of work. The author should be congratulated on gathering so many [pregnant] women who had had bariatric surgery. The work gives a unique glimpse into metabolic syndrome,” said Philip Toozs-Hobson, MD, who moderated the session.

“We are increasingly recognizing the impact [of bariatric surgery] on metabolic syndrome, and the fact that this study demonstrates that there is more to it than just weight is important,” continued Dr. Toosz-Hobson, who is a consultant gynecologist at Birmingham Women’s Hospital NHS Foundation Trust, United Kingdom.
 

Cardiovascular benefits of bariatric surgery

Bariatric surgery has been associated with loss of excess body weight of up to 55% and with approximately 40% reduction in all-cause mortality in the general population. The procedure also reduces the risk for heart disease, diabetes, and cancer.

The cardiovascular benefits of bariatric surgery include reduced hypertension, remodeling of the heart with a reduction in left ventricular mass, and an improvement in diastolic and systolic function.

“Traditionally, the cardiac changes were thought to be due to weight loss and blood pressure reduction, but it is now conceivable that the metabolic components contribute to the reverse modeling via changes to the enterocardiac axis involving changes to gut hormones,” said Dr. Patel. These hormones include secretin, glucagon, and vasoactive intestinal peptide, which are known to have inotropic effects, as well as adiponectin and leptin, which are known to have cardiac effects, she added.

“Pregnancy following bariatric surgery is associated with a reduced risk of hypertensive disorders, as well as a reduced risk of gestational diabetes, large-for-gestational-age neonates, and a small increased risk of small-for-gestational-age neonates,” said Dr. Patel.

Dr. Patel and Dr. Toosz-Hobson have disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Excessive drooling by patients with advanced Parkinson’s disease is an indicator of greater motor and nonmotor dysfunction, new research shows. “Sialorrhea is not just a cosmetic problem,” study investigator Francesca Morgante, MD, associate professor of neurology, St. George’s University, London, told this news organization.

“We need to understand the relationship between sialorrhea and these speech and swallowing disturbances and whether treatment for sialorrhea improves that,” Dr. Morgante added.

The findings were presented at the 2021 Congress of the European Academy of Neurology.
 

Underrecognized symptom

Sialorrhea is an underrecognized nonmotor symptom that can affect up to 70% of patients with Parkinson’s disease, said co-investigator Ioana Cociasu, PhD, postdoctoral research fellow, Neurosciences Research Center, St. George’s University. The impact on quality of life increases with disease severity, she said.

The current study included 101 consecutive patients attending an advanced Parkinson’s disease disorders clinic. Researchers collected demographic data that included information on gender, age, age at Parkinson’s disease onset, and disease duration. They also gathered data on motor symptoms by assessing total levodopa equivalent daily dose (LEDD) and LEDD dopamine agonists. They also assessed results on the Unified Parkinson’s Disease Rating Scale (UPDRS) part III and the Hoehn and Yahr scale for on- and off-medication states.

Nonmotor functioning was assessed using the Non-Motor Symptoms Scale (NMSS) and Scales for Outcomes in Parkinson’s disease–autonomic dysfunction (SCOPA-AUT) questionnaire. Among patients with Parkinson’s disease, autonomic dysfunction can precede motor impairment and can involve orthostatic and postprandial hypotension, among other symptoms, the investigators noted.

Health status and quality of life were assessed using the Parkinson’s disease questionnaire–39 items (PDQ-39). The Radboud Oral Motor Inventory for PD (ROMP) was used to measure orofacial symptoms. ROMP is a self-administered questionnaire that evaluates speech, swallowing disturbances, and drooling of saliva. The Montreal Cognitive Assessment test was also used.

Investigators compared participants with sialorrhea to those without sialorrhea, described as droolers and nondroolers. Droolers were defined as those scoring higher than 1 on the UPDRS-II item 6. This signified slight but definite presence of saliva in the mouth and/or the possibility of nighttime drooling.
 

Greater impairment

Among the participants, 65 (64.4%) were classified as droolers, and 36 (35.6%) as nondroolers.

Patients with both Parkinson’s disease and sialorrhea were significantly more impaired in terms of motor functioning than those without sialorrhea. In these patients, the UPDRS-III was more severe in both the off- (P = .03) and on-states (P = .002), and they had less improvement with the levodopa challenge test (P = .007).

Droolers were also more severely affected by nonmotor problems. They had more severe speech dysfunction (P < .0001) and swallowing dysfunction (P < .05), and they had higher scores on the NMSS (P = .0008) and SCOPA-AUT (P = .003) and poorer quality-of-life scores on the PDQ-39 (P = .049).

To evaluate respiratory tract infections, the researchers used electronic health records. About 15.4% of the study population had had a documented respiratory infection since they were diagnosed with Parkinson’s disease.

Upper and lower respiratory tract infections were more frequent among droolers than nondroolers (P = .05).

“Infections might arise from swallowing disturbances leading to aspiration and drooling,” Dr. Morgante noted.

The drooling did not appear to affect cognition or sleep in these patients.
 

Treatment options?

Following the study presentation, session co-chair Philippe G. Damier, MD, PhD, professor of neurology, University Hospital, Nantes, France, asked about the best treatment for sialorrhea for these patients.

In general, those with milder disease might try chewing gum to improve swallowing; patients with more severe cases may benefit from botulinum toxin injections, said Dr. Cociasu. The treatment choice, she added, “very much depends on the severity of the sialorrhea.”

Botulinum toxin therapy involves injections into the salivary gland to reduce saliva production. It is typically administered about every 4 months.

The second session co-chair, Elena Moro, MD, PhD, director of the Movement Disorders Unit at Grenoble Alpes University, France, pointed out that chewing gum may be a swallowing hazard for patients with PD and severe dementia.

Asked by Dr. Moro whether patients with higher scores on balance and posture were more likely to have sialorrhea, Dr. Cociasu said she and her colleagues are currently looking into this.

Dr. Morgante said that the current study did not examine the effect of treatment on speech disorders associated with sialorrhea. “We are running another study now to understand the effect of treatment of sialorrhea on these features,” she said.

Dr. Morgante and Dr. Cociasu have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A key molecular mechanism underpinning the anti-inflammatory, antidepressant, and neuroprotective effects of omega-3 fatty acids has been identified. In findings that could lead to the development of new treatments for depression, the research provides the “first evidence” that hippocampal neurons are able to produce two key lipid metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – lipoxygenase and cytochrome P450, lead investigator Alessandra Borsini, PhD, told this news organization.

This is how EPA and DHA exert their anti-inflammatory and neurogenic properties in vitro, as well as antidepressant properties in patients with depression, said Dr. Borsini, from King’s College London.

“Indeed, we found evidence for a correlation between increased levels of these metabolites and a decrease in severity of depressive symptoms in patients with major depressive disorder,” Dr. Borsini said.

The study was published online June 16 in Molecular Psychiatry.
 

‘Depression in a dish’

Despite the known role of inflammation in depression, there remains a lack of data showing anti-inflammatory strategies that are effective, safe for everyday use, and with a clear mechanism of action, the researchers note.  

Dr. Borsini and colleagues tested the theory that when EPA and DHA are metabolized, some of their metabolites, or lipid mediators, can protect the brain from the harmful effects of inflammation. They used a validated “depression in a dish” in vitro human hippocampal cell model to test their theory.

They found that treating human hippocampal cells with EPA or DHA before exposing them to cytokines prevented increased cell death and decreased neurogenesis. Both these impacts had been previously observed in cells exposed to cytokines alone.

They confirmed that these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA – namely hydroxyeicosapentaenoic acid, hydroxydocosahexaenoic acid, epoxyeicosatetraenoic acid (EpETE), and epoxydocosapentaenoic acid (EpDPA).

It’s the first time these lipid mediators were detected in human hippocampal neurons, the researchers say.

They also found that treating the neurons with an enzyme inhibitor increased the availability of two of these metabolites (EpETE and EpDPA), suggesting a possible way by which future treatments could be optimized.

The findings were replicated in 22 patients with major depression given either EPA (3 g/day) or DHA (1.4 g/day) for 12 weeks. In both groups, EPA or DHA treatment was associated with an increase in their respective metabolites and significant improvement in depressive symptoms.

The average reduction in symptom scores was 64% and 71% in the EPA and DHA groups, respectively, and there was some evidence that higher levels of the same metabolites correlated with less severe depressive symptoms.

“For some time we have known that omega-3 [polyunsaturated fatty acid (PUFA)] can induce antidepressant and anti-inflammatory effects, but, without further understanding of how this happens in the human brain, it has been difficult to develop treatments,” Dr. Borsini said in a news release.

“Our study has helped shine a light on the molecular mechanisms involved in this relationship which can inform the development of potential new treatments for depression using omega-3 PUFA,” Dr. Borsini added.

“We need to be cautious when interpreting data generated from the correlation between levels of metabolites and depressive symptoms as findings require further validation in a bigger sample of patients,” Dr. Borsini said.

“It is important to highlight that our research has not shown that by simply increasing omega-3 fatty acids in our diets or through taking nutritional supplements we can reduce inflammation or depression,” study author Carmine Pariante, MD, PhD, from King’s College London, said in the news release.

“The mechanisms behind the associations between depression and omega-3 PUFA are complicated and require further research and clinical trials to fully understand how they work and inform future therapeutic approaches,” Dr. Pariante said.
 

No clinical implications

Weighing in on this research in a Science Media Centre statement, Kevin McConway, emeritus professor of applied statistics, The Open University, Milton Keynes, United Kingdom, said, “The point of the study was to throw some light on the mechanisms in the body by which omega-3 fatty acids might work to reduce inflammation or depression.”

“The research mostly involved cells in laboratory dishes, but it also involved treating a small sample of patients with major depression by giving them supplements of one or other of the two omega-3 acids under investigation for 12 weeks,” he noted.

“The researchers found that the patients’ average scores on a standard set of questions, used to diagnose and measure depression, improved over that 12-week period, for each of the two fatty acids.

While depression symptoms improved over 12 weeks with omega-3 fatty acid treatment, “depression symptoms change over time anyway, for many reasons,” and depressive symptoms might have improved over 12 weeks even if the patients had not been given the omega-3 acids, Dr. McConway said.

“We just can’t tell since every patient got omega-3 fatty acids. So these results can hint that omega-3 fatty acids might help in depression, but it comes nowhere near showing that this is the case with a reasonable degree of certainty,” he cautioned.

“Indeed the researchers did not carry out this part of their study to see whether the omega-3 supplements help with depression – they did it to see whether the biochemical changes that they had seen in cell cultures in the lab might also occur in human bodies,” he noted.

This research was funded in part by grants to the investigators from the U.K. Medical Research Council, the European Commission Horizon 2020, and the National Institute for Health Research (NIHR), Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. Dr. Borsini has received research funding from Johnson & Johnson for research on depression and inflammation. Dr. McConway is a trustee of the Science Media Centre and a member of its advisory committee.

A version of this article first appeared on Medscape.com.

A key molecular mechanism underpinning the anti-inflammatory, antidepressant, and neuroprotective effects of omega-3 fatty acids has been identified. In findings that could lead to the development of new treatments for depression, the research provides the “first evidence” that hippocampal neurons are able to produce two key lipid metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – lipoxygenase and cytochrome P450, lead investigator Alessandra Borsini, PhD, told this news organization.

This is how EPA and DHA exert their anti-inflammatory and neurogenic properties in vitro, as well as antidepressant properties in patients with depression, said Dr. Borsini, from King’s College London.

“Indeed, we found evidence for a correlation between increased levels of these metabolites and a decrease in severity of depressive symptoms in patients with major depressive disorder,” Dr. Borsini said.

The study was published online June 16 in Molecular Psychiatry.
 

‘Depression in a dish’

Despite the known role of inflammation in depression, there remains a lack of data showing anti-inflammatory strategies that are effective, safe for everyday use, and with a clear mechanism of action, the researchers note.  

Dr. Borsini and colleagues tested the theory that when EPA and DHA are metabolized, some of their metabolites, or lipid mediators, can protect the brain from the harmful effects of inflammation. They used a validated “depression in a dish” in vitro human hippocampal cell model to test their theory.

They found that treating human hippocampal cells with EPA or DHA before exposing them to cytokines prevented increased cell death and decreased neurogenesis. Both these impacts had been previously observed in cells exposed to cytokines alone.

They confirmed that these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA – namely hydroxyeicosapentaenoic acid, hydroxydocosahexaenoic acid, epoxyeicosatetraenoic acid (EpETE), and epoxydocosapentaenoic acid (EpDPA).

It’s the first time these lipid mediators were detected in human hippocampal neurons, the researchers say.

They also found that treating the neurons with an enzyme inhibitor increased the availability of two of these metabolites (EpETE and EpDPA), suggesting a possible way by which future treatments could be optimized.

The findings were replicated in 22 patients with major depression given either EPA (3 g/day) or DHA (1.4 g/day) for 12 weeks. In both groups, EPA or DHA treatment was associated with an increase in their respective metabolites and significant improvement in depressive symptoms.

The average reduction in symptom scores was 64% and 71% in the EPA and DHA groups, respectively, and there was some evidence that higher levels of the same metabolites correlated with less severe depressive symptoms.

“For some time we have known that omega-3 [polyunsaturated fatty acid (PUFA)] can induce antidepressant and anti-inflammatory effects, but, without further understanding of how this happens in the human brain, it has been difficult to develop treatments,” Dr. Borsini said in a news release.

“Our study has helped shine a light on the molecular mechanisms involved in this relationship which can inform the development of potential new treatments for depression using omega-3 PUFA,” Dr. Borsini added.

“We need to be cautious when interpreting data generated from the correlation between levels of metabolites and depressive symptoms as findings require further validation in a bigger sample of patients,” Dr. Borsini said.

“It is important to highlight that our research has not shown that by simply increasing omega-3 fatty acids in our diets or through taking nutritional supplements we can reduce inflammation or depression,” study author Carmine Pariante, MD, PhD, from King’s College London, said in the news release.

“The mechanisms behind the associations between depression and omega-3 PUFA are complicated and require further research and clinical trials to fully understand how they work and inform future therapeutic approaches,” Dr. Pariante said.
 

No clinical implications

Weighing in on this research in a Science Media Centre statement, Kevin McConway, emeritus professor of applied statistics, The Open University, Milton Keynes, United Kingdom, said, “The point of the study was to throw some light on the mechanisms in the body by which omega-3 fatty acids might work to reduce inflammation or depression.”

“The research mostly involved cells in laboratory dishes, but it also involved treating a small sample of patients with major depression by giving them supplements of one or other of the two omega-3 acids under investigation for 12 weeks,” he noted.

“The researchers found that the patients’ average scores on a standard set of questions, used to diagnose and measure depression, improved over that 12-week period, for each of the two fatty acids.

While depression symptoms improved over 12 weeks with omega-3 fatty acid treatment, “depression symptoms change over time anyway, for many reasons,” and depressive symptoms might have improved over 12 weeks even if the patients had not been given the omega-3 acids, Dr. McConway said.

“We just can’t tell since every patient got omega-3 fatty acids. So these results can hint that omega-3 fatty acids might help in depression, but it comes nowhere near showing that this is the case with a reasonable degree of certainty,” he cautioned.

“Indeed the researchers did not carry out this part of their study to see whether the omega-3 supplements help with depression – they did it to see whether the biochemical changes that they had seen in cell cultures in the lab might also occur in human bodies,” he noted.

This research was funded in part by grants to the investigators from the U.K. Medical Research Council, the European Commission Horizon 2020, and the National Institute for Health Research (NIHR), Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. Dr. Borsini has received research funding from Johnson & Johnson for research on depression and inflammation. Dr. McConway is a trustee of the Science Media Centre and a member of its advisory committee.

A version of this article first appeared on Medscape.com.

A key molecular mechanism underpinning the anti-inflammatory, antidepressant, and neuroprotective effects of omega-3 fatty acids has been identified. In findings that could lead to the development of new treatments for depression, the research provides the “first evidence” that hippocampal neurons are able to produce two key lipid metabolites of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) – lipoxygenase and cytochrome P450, lead investigator Alessandra Borsini, PhD, told this news organization.

This is how EPA and DHA exert their anti-inflammatory and neurogenic properties in vitro, as well as antidepressant properties in patients with depression, said Dr. Borsini, from King’s College London.

“Indeed, we found evidence for a correlation between increased levels of these metabolites and a decrease in severity of depressive symptoms in patients with major depressive disorder,” Dr. Borsini said.

The study was published online June 16 in Molecular Psychiatry.
 

‘Depression in a dish’

Despite the known role of inflammation in depression, there remains a lack of data showing anti-inflammatory strategies that are effective, safe for everyday use, and with a clear mechanism of action, the researchers note.  

Dr. Borsini and colleagues tested the theory that when EPA and DHA are metabolized, some of their metabolites, or lipid mediators, can protect the brain from the harmful effects of inflammation. They used a validated “depression in a dish” in vitro human hippocampal cell model to test their theory.

They found that treating human hippocampal cells with EPA or DHA before exposing them to cytokines prevented increased cell death and decreased neurogenesis. Both these impacts had been previously observed in cells exposed to cytokines alone.

They confirmed that these effects were mediated by the formation of several key lipid mediators produced by EPA and DHA – namely hydroxyeicosapentaenoic acid, hydroxydocosahexaenoic acid, epoxyeicosatetraenoic acid (EpETE), and epoxydocosapentaenoic acid (EpDPA).

It’s the first time these lipid mediators were detected in human hippocampal neurons, the researchers say.

They also found that treating the neurons with an enzyme inhibitor increased the availability of two of these metabolites (EpETE and EpDPA), suggesting a possible way by which future treatments could be optimized.

The findings were replicated in 22 patients with major depression given either EPA (3 g/day) or DHA (1.4 g/day) for 12 weeks. In both groups, EPA or DHA treatment was associated with an increase in their respective metabolites and significant improvement in depressive symptoms.

The average reduction in symptom scores was 64% and 71% in the EPA and DHA groups, respectively, and there was some evidence that higher levels of the same metabolites correlated with less severe depressive symptoms.

“For some time we have known that omega-3 [polyunsaturated fatty acid (PUFA)] can induce antidepressant and anti-inflammatory effects, but, without further understanding of how this happens in the human brain, it has been difficult to develop treatments,” Dr. Borsini said in a news release.

“Our study has helped shine a light on the molecular mechanisms involved in this relationship which can inform the development of potential new treatments for depression using omega-3 PUFA,” Dr. Borsini added.

“We need to be cautious when interpreting data generated from the correlation between levels of metabolites and depressive symptoms as findings require further validation in a bigger sample of patients,” Dr. Borsini said.

“It is important to highlight that our research has not shown that by simply increasing omega-3 fatty acids in our diets or through taking nutritional supplements we can reduce inflammation or depression,” study author Carmine Pariante, MD, PhD, from King’s College London, said in the news release.

“The mechanisms behind the associations between depression and omega-3 PUFA are complicated and require further research and clinical trials to fully understand how they work and inform future therapeutic approaches,” Dr. Pariante said.
 

No clinical implications

Weighing in on this research in a Science Media Centre statement, Kevin McConway, emeritus professor of applied statistics, The Open University, Milton Keynes, United Kingdom, said, “The point of the study was to throw some light on the mechanisms in the body by which omega-3 fatty acids might work to reduce inflammation or depression.”

“The research mostly involved cells in laboratory dishes, but it also involved treating a small sample of patients with major depression by giving them supplements of one or other of the two omega-3 acids under investigation for 12 weeks,” he noted.

“The researchers found that the patients’ average scores on a standard set of questions, used to diagnose and measure depression, improved over that 12-week period, for each of the two fatty acids.

While depression symptoms improved over 12 weeks with omega-3 fatty acid treatment, “depression symptoms change over time anyway, for many reasons,” and depressive symptoms might have improved over 12 weeks even if the patients had not been given the omega-3 acids, Dr. McConway said.

“We just can’t tell since every patient got omega-3 fatty acids. So these results can hint that omega-3 fatty acids might help in depression, but it comes nowhere near showing that this is the case with a reasonable degree of certainty,” he cautioned.

“Indeed the researchers did not carry out this part of their study to see whether the omega-3 supplements help with depression – they did it to see whether the biochemical changes that they had seen in cell cultures in the lab might also occur in human bodies,” he noted.

This research was funded in part by grants to the investigators from the U.K. Medical Research Council, the European Commission Horizon 2020, and the National Institute for Health Research (NIHR), Maudsley Biomedical Research Centre (BRC) at South London and Maudsley NHS Foundation Trust and King’s College London. Dr. Borsini has received research funding from Johnson & Johnson for research on depression and inflammation. Dr. McConway is a trustee of the Science Media Centre and a member of its advisory committee.

A version of this article first appeared on Medscape.com.

Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.

In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.

Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.

The article was published online June 14, 2021, in JAMA Network Open.

Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.

Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”

The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.

The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.

Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.

Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)

The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.

“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
 

Findings no surprise

Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.

“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.

Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.

Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.

“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.

Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”

The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.

In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.

Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.

The article was published online June 14, 2021, in JAMA Network Open.

Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.

Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”

The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.

The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.

Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.

Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)

The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.

“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
 

Findings no surprise

Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.

“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.

Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.

Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.

“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.

Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”

The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.

In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.

Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.

The article was published online June 14, 2021, in JAMA Network Open.

Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.

Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”

The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.

The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.

Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.

Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)

The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.

“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
 

Findings no surprise

Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.

“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.

Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.

Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.

“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.

Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”

The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions, according to results of a pivotal trial presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire, according to Sharief Taraman, MD, a pediatric neurologist at CHOC, a pediatric health care system in Orange County, Calif.

Although the device could be employed in a variety of settings, it is envisioned for use by primary care physicians. This will circumvent the need for specialist evaluation except in challenging cases. Currently, nearly all children with ASD are diagnosed in specialty care, according to data cited by Dr. Taraman.

“The lack of diagnostic tools for ASD in primary care settings contributes to an average delay of 3 years between first parental concern and diagnosis and to long wait lists for specialty evaluation,” he reported at the virtual meeting, presented by MedscapeLive.

When used with clinical judgment and criteria from the American Psychiatric Association’s 5th edition of the Diagnostic and Statistical Manual (DSM-5), the data from the trial suggest the diagnostic tool in the hands of primary care physicians “could efficiently and accurately assess ASD in children 18 to 72 months old,” said Dr. Taraman, also an associate clinical professor of pediatrics at the University of California, Irvine.*

The AI-assisted software was evaluated in 425 children at 14 sites in 6 states. The study population was reflective of U.S. demographics. Although only 36% of the children were female, this is consistent with ASD prevalence. Only 60% of the subjects were White. Nearly 30% were Black or Latinx and other populations, such as those of Asian heritage, were represented.

Children between the ages of 18 and 72 months were eligible if both a caregiver and a health care professional were concerned that the child had ASD. About the same time that a caregiver completed a 20-item questionnaire and the primary care physician completed a 15-item questionnaire on a mobile device, the caregiver uploaded two videos of 1-2 minutes in length.

This information, along with a 33-item questionnaire completed by an analyst of the submitted videos, was then processed by the software algorithm. It provided a patient status of positive or negative for ASD, or it concluded that the status was indeterminate.

“To reduce the risk of false classifications, the indeterminate status was included as a safety feature,” Dr. Taraman explained. However, Dr. Taraman considers an indeterminate designation potentially actionable. Rather than a negative result, this status suggests a complex neurodevelopmental disorder and indicates the need for further evaluation.

The reference standard diagnosis, completed in all participants in this study, was a specialist evaluation completed independently by two experts. The presence or absence of ASD was confirmed if the experts agreed. If they did not, a third specialist made the final determination.

On the basis of the software, there was a determinate result in 52% of the children. In comparison to the specialist determinations, all were correctly classified except for one child, in which the software was determined to have made a false-negative diagnosis. A diagnosis of ASD was reached in 29% of the study participants.

For those with a determinate designation, the sensitivity was 98.4% and the specificity was 78.9%. This translated into positive predictive and negative predictive values of 80.8% and 98.3%, respectively.

Of those identified as indeterminate by the AI-assisted algorithm, 91% were ultimately considered by specialist evaluation to have complex issues. In this group, ASD was part of the complex clinical picture in 20%. The others had non-ASD neurodevelopmental conditions, according to Dr. Taraman.

When the accuracy was evaluated across ages, ethnicity, and factors such as parent education or family income, the tool performed consistently, Dr. Taraman reported. This is important, he said, because the presence or absence of ASD is misdiagnosed in many underserved populations.

The focus on developing a methodology specific for use in primary care was based on evidence that the delay in the diagnosis of ASD is attributable to long wait times for specialty evaluations.

“There will never be enough specialists. There is a need for a way to streamline the diagnosis of ASD,” Dr. Taraman maintained. This is helpful not only to parents concerned about their children, he said, but also there are data to suggest that early intervention improves outcomes.

A specialist in ASD, Paul Carbone, MD, medical director of the child development program at the University of Utah, Salt Lake City, agreed. He said early diagnosis and intervention should be a goal.

“Reducing the age of ASD diagnosis is a priority because early entry into autism-specific interventions is a strong predictor of optimal developmental outcomes for children,” Dr. Carbone said.

Although he is not familiar with this experimental AI-assisted diagnostic program, he has published on the feasibility of ASD diagnosis at the primary care level. In his study, Dr. Carbone examined the Modified Checklist for Autism in Toddlers (M-CHAT) as one of several methodologies that might be considered.

Diagnosis of ASD “can be achieved through systematic processes within primary care that facilitate universal development surveillance and autism screening followed by prompt and timely diagnostic evaluations of at-risk children,” Dr. Carbone said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Taraman reported a financial relationship with Cognoa, the company that is developing the ASD software for clinical use. Dr. Carbone reported that he has no conflicts of interest.

*Updated, 7/7/21

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions, according to results of a pivotal trial presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire, according to Sharief Taraman, MD, a pediatric neurologist at CHOC, a pediatric health care system in Orange County, Calif.

Although the device could be employed in a variety of settings, it is envisioned for use by primary care physicians. This will circumvent the need for specialist evaluation except in challenging cases. Currently, nearly all children with ASD are diagnosed in specialty care, according to data cited by Dr. Taraman.

“The lack of diagnostic tools for ASD in primary care settings contributes to an average delay of 3 years between first parental concern and diagnosis and to long wait lists for specialty evaluation,” he reported at the virtual meeting, presented by MedscapeLive.

When used with clinical judgment and criteria from the American Psychiatric Association’s 5th edition of the Diagnostic and Statistical Manual (DSM-5), the data from the trial suggest the diagnostic tool in the hands of primary care physicians “could efficiently and accurately assess ASD in children 18 to 72 months old,” said Dr. Taraman, also an associate clinical professor of pediatrics at the University of California, Irvine.*

The AI-assisted software was evaluated in 425 children at 14 sites in 6 states. The study population was reflective of U.S. demographics. Although only 36% of the children were female, this is consistent with ASD prevalence. Only 60% of the subjects were White. Nearly 30% were Black or Latinx and other populations, such as those of Asian heritage, were represented.

Children between the ages of 18 and 72 months were eligible if both a caregiver and a health care professional were concerned that the child had ASD. About the same time that a caregiver completed a 20-item questionnaire and the primary care physician completed a 15-item questionnaire on a mobile device, the caregiver uploaded two videos of 1-2 minutes in length.

This information, along with a 33-item questionnaire completed by an analyst of the submitted videos, was then processed by the software algorithm. It provided a patient status of positive or negative for ASD, or it concluded that the status was indeterminate.

“To reduce the risk of false classifications, the indeterminate status was included as a safety feature,” Dr. Taraman explained. However, Dr. Taraman considers an indeterminate designation potentially actionable. Rather than a negative result, this status suggests a complex neurodevelopmental disorder and indicates the need for further evaluation.

The reference standard diagnosis, completed in all participants in this study, was a specialist evaluation completed independently by two experts. The presence or absence of ASD was confirmed if the experts agreed. If they did not, a third specialist made the final determination.

On the basis of the software, there was a determinate result in 52% of the children. In comparison to the specialist determinations, all were correctly classified except for one child, in which the software was determined to have made a false-negative diagnosis. A diagnosis of ASD was reached in 29% of the study participants.

For those with a determinate designation, the sensitivity was 98.4% and the specificity was 78.9%. This translated into positive predictive and negative predictive values of 80.8% and 98.3%, respectively.

Of those identified as indeterminate by the AI-assisted algorithm, 91% were ultimately considered by specialist evaluation to have complex issues. In this group, ASD was part of the complex clinical picture in 20%. The others had non-ASD neurodevelopmental conditions, according to Dr. Taraman.

When the accuracy was evaluated across ages, ethnicity, and factors such as parent education or family income, the tool performed consistently, Dr. Taraman reported. This is important, he said, because the presence or absence of ASD is misdiagnosed in many underserved populations.

The focus on developing a methodology specific for use in primary care was based on evidence that the delay in the diagnosis of ASD is attributable to long wait times for specialty evaluations.

“There will never be enough specialists. There is a need for a way to streamline the diagnosis of ASD,” Dr. Taraman maintained. This is helpful not only to parents concerned about their children, he said, but also there are data to suggest that early intervention improves outcomes.

A specialist in ASD, Paul Carbone, MD, medical director of the child development program at the University of Utah, Salt Lake City, agreed. He said early diagnosis and intervention should be a goal.

“Reducing the age of ASD diagnosis is a priority because early entry into autism-specific interventions is a strong predictor of optimal developmental outcomes for children,” Dr. Carbone said.

Although he is not familiar with this experimental AI-assisted diagnostic program, he has published on the feasibility of ASD diagnosis at the primary care level. In his study, Dr. Carbone examined the Modified Checklist for Autism in Toddlers (M-CHAT) as one of several methodologies that might be considered.

Diagnosis of ASD “can be achieved through systematic processes within primary care that facilitate universal development surveillance and autism screening followed by prompt and timely diagnostic evaluations of at-risk children,” Dr. Carbone said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Taraman reported a financial relationship with Cognoa, the company that is developing the ASD software for clinical use. Dr. Carbone reported that he has no conflicts of interest.

*Updated, 7/7/21

A software program based on artificial intelligence (AI) is effective for distinguishing young children with autism spectrum disorder (ASD) from those with other conditions, according to results of a pivotal trial presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

The AI-based software, which will be submitted to regulatory approval as a device, employs an algorithm that assembles inputs from a caregiver questionnaire, a video, and a clinician questionnaire, according to Sharief Taraman, MD, a pediatric neurologist at CHOC, a pediatric health care system in Orange County, Calif.

Although the device could be employed in a variety of settings, it is envisioned for use by primary care physicians. This will circumvent the need for specialist evaluation except in challenging cases. Currently, nearly all children with ASD are diagnosed in specialty care, according to data cited by Dr. Taraman.

“The lack of diagnostic tools for ASD in primary care settings contributes to an average delay of 3 years between first parental concern and diagnosis and to long wait lists for specialty evaluation,” he reported at the virtual meeting, presented by MedscapeLive.

When used with clinical judgment and criteria from the American Psychiatric Association’s 5th edition of the Diagnostic and Statistical Manual (DSM-5), the data from the trial suggest the diagnostic tool in the hands of primary care physicians “could efficiently and accurately assess ASD in children 18 to 72 months old,” said Dr. Taraman, also an associate clinical professor of pediatrics at the University of California, Irvine.*

The AI-assisted software was evaluated in 425 children at 14 sites in 6 states. The study population was reflective of U.S. demographics. Although only 36% of the children were female, this is consistent with ASD prevalence. Only 60% of the subjects were White. Nearly 30% were Black or Latinx and other populations, such as those of Asian heritage, were represented.

Children between the ages of 18 and 72 months were eligible if both a caregiver and a health care professional were concerned that the child had ASD. About the same time that a caregiver completed a 20-item questionnaire and the primary care physician completed a 15-item questionnaire on a mobile device, the caregiver uploaded two videos of 1-2 minutes in length.

This information, along with a 33-item questionnaire completed by an analyst of the submitted videos, was then processed by the software algorithm. It provided a patient status of positive or negative for ASD, or it concluded that the status was indeterminate.

“To reduce the risk of false classifications, the indeterminate status was included as a safety feature,” Dr. Taraman explained. However, Dr. Taraman considers an indeterminate designation potentially actionable. Rather than a negative result, this status suggests a complex neurodevelopmental disorder and indicates the need for further evaluation.

The reference standard diagnosis, completed in all participants in this study, was a specialist evaluation completed independently by two experts. The presence or absence of ASD was confirmed if the experts agreed. If they did not, a third specialist made the final determination.

On the basis of the software, there was a determinate result in 52% of the children. In comparison to the specialist determinations, all were correctly classified except for one child, in which the software was determined to have made a false-negative diagnosis. A diagnosis of ASD was reached in 29% of the study participants.

For those with a determinate designation, the sensitivity was 98.4% and the specificity was 78.9%. This translated into positive predictive and negative predictive values of 80.8% and 98.3%, respectively.

Of those identified as indeterminate by the AI-assisted algorithm, 91% were ultimately considered by specialist evaluation to have complex issues. In this group, ASD was part of the complex clinical picture in 20%. The others had non-ASD neurodevelopmental conditions, according to Dr. Taraman.

When the accuracy was evaluated across ages, ethnicity, and factors such as parent education or family income, the tool performed consistently, Dr. Taraman reported. This is important, he said, because the presence or absence of ASD is misdiagnosed in many underserved populations.

The focus on developing a methodology specific for use in primary care was based on evidence that the delay in the diagnosis of ASD is attributable to long wait times for specialty evaluations.

“There will never be enough specialists. There is a need for a way to streamline the diagnosis of ASD,” Dr. Taraman maintained. This is helpful not only to parents concerned about their children, he said, but also there are data to suggest that early intervention improves outcomes.

A specialist in ASD, Paul Carbone, MD, medical director of the child development program at the University of Utah, Salt Lake City, agreed. He said early diagnosis and intervention should be a goal.

“Reducing the age of ASD diagnosis is a priority because early entry into autism-specific interventions is a strong predictor of optimal developmental outcomes for children,” Dr. Carbone said.

Although he is not familiar with this experimental AI-assisted diagnostic program, he has published on the feasibility of ASD diagnosis at the primary care level. In his study, Dr. Carbone examined the Modified Checklist for Autism in Toddlers (M-CHAT) as one of several methodologies that might be considered.

Diagnosis of ASD “can be achieved through systematic processes within primary care that facilitate universal development surveillance and autism screening followed by prompt and timely diagnostic evaluations of at-risk children,” Dr. Carbone said.

MedscapeLive and this news organization are owned by the same parent company. Dr. Taraman reported a financial relationship with Cognoa, the company that is developing the ASD software for clinical use. Dr. Carbone reported that he has no conflicts of interest.

*Updated, 7/7/21

Dr. Richard Furie presents highlights in systemic lupus erythematosus (SLE) and its various complications—such as lupus nephritis (LN), pulmonary involvement, and cutaneous manifestations—from the EULAR 2021 Virtual Congress.

The 6-month open-label extension of BLISS-LN assessed patients with LN after 2 years of double-blind treatment. Primary efficacy renal response and complete renal response (CRR) increased in both the belimumab-naïve and belimumab-experienced groups, with no new safety concerns.

The phase 2 TULIP-LN trial evaluated anifrolumab vs placebo alongside standard therapy in patients with active proliferative LN. Anifrolumab 900 mg for 3 doses, 300 mg thereafter was associated with improvements in CRR at week 52.

Another phase 2 study assessed BI 655064 vs placebo in patients with active proliferative LN. A high response to placebo prompted an exploratory analysis requiring confirmation of endpoint during weeks 46 and 52. Proportions of patients achieving confirmed CRR were higher in the 180- and 240-mg dosing groups vs placebo.

A single-center cohort of 300 patients assessed the frequency of pulmonary involvement; 16% had interstitial lung disease, nearly 7% had pulmonary hypertension, and 3% had shrinking lung syndrome.

The last 2 presentations are on cutaneous lupus. In one study, iberdomide had beneficial effects on cutaneous manifestations in patients with SLE, particularly those with subacute and chronic acute subtypes as well as those with high Aiolos or interferon gene expression signatures.

Lastly, a post hoc analysis of a phase 2 study evaluated the effects of BIIB059 on cutaneous lupus, and found that a greater proportion of participants achieved milder skin disease or clear/almost clear skin status in the BIIB059 groups vs placebo.

--

Professor, Department of Medicine, Zucker School of Medicine, Hofstra/Northwell, Hempstead;
Chief, Department of Medicine, Division of Rheumatology, Northwell Health
Great Neck, New York

Richard Furie, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Biogen; Boehringer Ingelheim; Bristol-Myers Squibb; GlaxoSmithKline

Received research grant from: AstraZeneca; Biogen; Bristol-Myers Squibb; Boehringer Ingelheim; GlaxoSmithKline

Received income in an amount equal to or greater than $250 from: AstraZeneca; Biogen; Bristol-Myers Squibb; Boehringer Ingelheim; GlaxoSmithKline

Dr. Richard Furie presents highlights in systemic lupus erythematosus (SLE) and its various complications—such as lupus nephritis (LN), pulmonary involvement, and cutaneous manifestations—from the EULAR 2021 Virtual Congress.

The 6-month open-label extension of BLISS-LN assessed patients with LN after 2 years of double-blind treatment. Primary efficacy renal response and complete renal response (CRR) increased in both the belimumab-naïve and belimumab-experienced groups, with no new safety concerns.

The phase 2 TULIP-LN trial evaluated anifrolumab vs placebo alongside standard therapy in patients with active proliferative LN. Anifrolumab 900 mg for 3 doses, 300 mg thereafter was associated with improvements in CRR at week 52.

Another phase 2 study assessed BI 655064 vs placebo in patients with active proliferative LN. A high response to placebo prompted an exploratory analysis requiring confirmation of endpoint during weeks 46 and 52. Proportions of patients achieving confirmed CRR were higher in the 180- and 240-mg dosing groups vs placebo.

A single-center cohort of 300 patients assessed the frequency of pulmonary involvement; 16% had interstitial lung disease, nearly 7% had pulmonary hypertension, and 3% had shrinking lung syndrome.

The last 2 presentations are on cutaneous lupus. In one study, iberdomide had beneficial effects on cutaneous manifestations in patients with SLE, particularly those with subacute and chronic acute subtypes as well as those with high Aiolos or interferon gene expression signatures.

Lastly, a post hoc analysis of a phase 2 study evaluated the effects of BIIB059 on cutaneous lupus, and found that a greater proportion of participants achieved milder skin disease or clear/almost clear skin status in the BIIB059 groups vs placebo.

--

Professor, Department of Medicine, Zucker School of Medicine, Hofstra/Northwell, Hempstead;
Chief, Department of Medicine, Division of Rheumatology, Northwell Health
Great Neck, New York

Richard Furie, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Biogen; Boehringer Ingelheim; Bristol-Myers Squibb; GlaxoSmithKline

Received research grant from: AstraZeneca; Biogen; Bristol-Myers Squibb; Boehringer Ingelheim; GlaxoSmithKline

Received income in an amount equal to or greater than $250 from: AstraZeneca; Biogen; Bristol-Myers Squibb; Boehringer Ingelheim; GlaxoSmithKline

Dr. Richard Furie presents highlights in systemic lupus erythematosus (SLE) and its various complications—such as lupus nephritis (LN), pulmonary involvement, and cutaneous manifestations—from the EULAR 2021 Virtual Congress.

The 6-month open-label extension of BLISS-LN assessed patients with LN after 2 years of double-blind treatment. Primary efficacy renal response and complete renal response (CRR) increased in both the belimumab-naïve and belimumab-experienced groups, with no new safety concerns.

The phase 2 TULIP-LN trial evaluated anifrolumab vs placebo alongside standard therapy in patients with active proliferative LN. Anifrolumab 900 mg for 3 doses, 300 mg thereafter was associated with improvements in CRR at week 52.

Another phase 2 study assessed BI 655064 vs placebo in patients with active proliferative LN. A high response to placebo prompted an exploratory analysis requiring confirmation of endpoint during weeks 46 and 52. Proportions of patients achieving confirmed CRR were higher in the 180- and 240-mg dosing groups vs placebo.

A single-center cohort of 300 patients assessed the frequency of pulmonary involvement; 16% had interstitial lung disease, nearly 7% had pulmonary hypertension, and 3% had shrinking lung syndrome.

The last 2 presentations are on cutaneous lupus. In one study, iberdomide had beneficial effects on cutaneous manifestations in patients with SLE, particularly those with subacute and chronic acute subtypes as well as those with high Aiolos or interferon gene expression signatures.

Lastly, a post hoc analysis of a phase 2 study evaluated the effects of BIIB059 on cutaneous lupus, and found that a greater proportion of participants achieved milder skin disease or clear/almost clear skin status in the BIIB059 groups vs placebo.

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Professor, Department of Medicine, Zucker School of Medicine, Hofstra/Northwell, Hempstead;
Chief, Department of Medicine, Division of Rheumatology, Northwell Health
Great Neck, New York

Richard Furie, MD, has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: AstraZeneca; Biogen; Boehringer Ingelheim; Bristol-Myers Squibb; GlaxoSmithKline

Received research grant from: AstraZeneca; Biogen; Bristol-Myers Squibb; Boehringer Ingelheim; GlaxoSmithKline

Received income in an amount equal to or greater than $250 from: AstraZeneca; Biogen; Bristol-Myers Squibb; Boehringer Ingelheim; GlaxoSmithKline