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Mitchel is a reporter for MDedge based in the Philadelphia area. He started with the company in 1992, when it was International Medical News Group (IMNG), and has since covered a range of medical specialties. Mitchel trained as a virologist at Roswell Park Memorial Institute in Buffalo, and then worked briefly as a researcher at Boston Children's Hospital before pivoting to journalism as a AAAS Mass Media Fellow in 1980. His first reporting job was with Science Digest magazine, and from the mid-1980s to early-1990s he was a reporter with Medical World News. @mitchelzoler
Lymphoma risk prompts FDA recall of Allergan’s textured breast implants
The Food and Drug Administration requested on July 24 that Allergan pull six brands of textured breast implants and breast expanders from the U.S. market, an action the agency took because of new data that substantially increased the number of women who developed a rare cancer – anaplastic large-cell lymphoma – in association with receiving these textured breast devices.
This is the first product recall the FDA has made to address the issue of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), a complication that first came to national attention with a 2011 FDA report that had tallied 60 identified BIA-ALCL cases worldwide. By the end of September 2018, the number of reported worldwide BIA-ALCL cases had jumped to 457 cases reported to the agency via medical device reporting. In July 2019, the FDA cited a total of 573 unique, global case reports for BIA-ALCL sent to the agency through July 6, including 33 episodes that led to death.
It was inclusion of these additional 116 cases since September 2018 and 24 additional deaths that led FDA researchers to conclude that “the risk of BIA-ALCL with Allergan BIOCELL textured implants is approximately six-times the risk of BIA-ALCL with textured implants from other manufacturers marketing in the U.S.,” according to a statement from the agency.
The FDA is not recommending that patients who received one of the six products covered by the recall have the material removed if symptoms have not appeared because of the potential risk from explantation.
The agency also stressed that its investigation of the risk posed by placement of other brands of textured breast implants is ongoing and that overall less than 5% of all breast implants performed in current U.S. practice involve the macrotextured implants of the type specified in the Allergan recall.
This U.S. recall follows similar actions taken in France (and the rest of the European Union), Canada, and Australia, and it contrasts with the agency’s prior decision in May 2019 not to start a recall or ban of textured implants following a advisory committee meeting that discussed BIA-ALCL.
The six products that Allergan agreed to recall from marketing at the FDA’s request are four textured breast implants (Natrelle Saline-Filled Breast Implants, Natrelle Silicone-Filled Breast Implants, Natrelle Inspira Silicone-Filled breast Implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants) and two tissue expanders used prior to a breast implant (Natrelle 133 Plus Tissue Expander and the Natrelle 133 Tissue Expander with Suture Tabs).
FDA officials said they are considering recommendations for changes to the labeling of breast implant products, including a possible boxed warning and beefed up patient information.
“The recall of these textured implants is a big deal in protecting women from the potential risks of developing, and dying from, this rare type of aggressive lymphoma,” Joshua Brody, MD, a medical oncologist and director of the lymphoma immunotherapy program at Mount Sinai Medical Center in New York said in a statement. “While case reports have suggested a potential link between some types of breast implants and this disease – anaplastic lymphoma – for over 20 years, it has taken time to gain sufficient evidence to suggest, and understand, the causality. Some types of implants induce inflammation, which can both increase the chance of developing cancer, and also help to ‘hide’ developing cancers from the immune system. By preventing further use of these implants, the FDA is helping women to protect themselves from the medically serious and emotionally exhausting effects of these risks.”
Dr. Brody reported having no relevant disclosures.
The Food and Drug Administration requested on July 24 that Allergan pull six brands of textured breast implants and breast expanders from the U.S. market, an action the agency took because of new data that substantially increased the number of women who developed a rare cancer – anaplastic large-cell lymphoma – in association with receiving these textured breast devices.
This is the first product recall the FDA has made to address the issue of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), a complication that first came to national attention with a 2011 FDA report that had tallied 60 identified BIA-ALCL cases worldwide. By the end of September 2018, the number of reported worldwide BIA-ALCL cases had jumped to 457 cases reported to the agency via medical device reporting. In July 2019, the FDA cited a total of 573 unique, global case reports for BIA-ALCL sent to the agency through July 6, including 33 episodes that led to death.
It was inclusion of these additional 116 cases since September 2018 and 24 additional deaths that led FDA researchers to conclude that “the risk of BIA-ALCL with Allergan BIOCELL textured implants is approximately six-times the risk of BIA-ALCL with textured implants from other manufacturers marketing in the U.S.,” according to a statement from the agency.
The FDA is not recommending that patients who received one of the six products covered by the recall have the material removed if symptoms have not appeared because of the potential risk from explantation.
The agency also stressed that its investigation of the risk posed by placement of other brands of textured breast implants is ongoing and that overall less than 5% of all breast implants performed in current U.S. practice involve the macrotextured implants of the type specified in the Allergan recall.
This U.S. recall follows similar actions taken in France (and the rest of the European Union), Canada, and Australia, and it contrasts with the agency’s prior decision in May 2019 not to start a recall or ban of textured implants following a advisory committee meeting that discussed BIA-ALCL.
The six products that Allergan agreed to recall from marketing at the FDA’s request are four textured breast implants (Natrelle Saline-Filled Breast Implants, Natrelle Silicone-Filled Breast Implants, Natrelle Inspira Silicone-Filled breast Implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants) and two tissue expanders used prior to a breast implant (Natrelle 133 Plus Tissue Expander and the Natrelle 133 Tissue Expander with Suture Tabs).
FDA officials said they are considering recommendations for changes to the labeling of breast implant products, including a possible boxed warning and beefed up patient information.
“The recall of these textured implants is a big deal in protecting women from the potential risks of developing, and dying from, this rare type of aggressive lymphoma,” Joshua Brody, MD, a medical oncologist and director of the lymphoma immunotherapy program at Mount Sinai Medical Center in New York said in a statement. “While case reports have suggested a potential link between some types of breast implants and this disease – anaplastic lymphoma – for over 20 years, it has taken time to gain sufficient evidence to suggest, and understand, the causality. Some types of implants induce inflammation, which can both increase the chance of developing cancer, and also help to ‘hide’ developing cancers from the immune system. By preventing further use of these implants, the FDA is helping women to protect themselves from the medically serious and emotionally exhausting effects of these risks.”
Dr. Brody reported having no relevant disclosures.
The Food and Drug Administration requested on July 24 that Allergan pull six brands of textured breast implants and breast expanders from the U.S. market, an action the agency took because of new data that substantially increased the number of women who developed a rare cancer – anaplastic large-cell lymphoma – in association with receiving these textured breast devices.
This is the first product recall the FDA has made to address the issue of breast implant–associated anaplastic large-cell lymphoma (BIA-ALCL), a complication that first came to national attention with a 2011 FDA report that had tallied 60 identified BIA-ALCL cases worldwide. By the end of September 2018, the number of reported worldwide BIA-ALCL cases had jumped to 457 cases reported to the agency via medical device reporting. In July 2019, the FDA cited a total of 573 unique, global case reports for BIA-ALCL sent to the agency through July 6, including 33 episodes that led to death.
It was inclusion of these additional 116 cases since September 2018 and 24 additional deaths that led FDA researchers to conclude that “the risk of BIA-ALCL with Allergan BIOCELL textured implants is approximately six-times the risk of BIA-ALCL with textured implants from other manufacturers marketing in the U.S.,” according to a statement from the agency.
The FDA is not recommending that patients who received one of the six products covered by the recall have the material removed if symptoms have not appeared because of the potential risk from explantation.
The agency also stressed that its investigation of the risk posed by placement of other brands of textured breast implants is ongoing and that overall less than 5% of all breast implants performed in current U.S. practice involve the macrotextured implants of the type specified in the Allergan recall.
This U.S. recall follows similar actions taken in France (and the rest of the European Union), Canada, and Australia, and it contrasts with the agency’s prior decision in May 2019 not to start a recall or ban of textured implants following a advisory committee meeting that discussed BIA-ALCL.
The six products that Allergan agreed to recall from marketing at the FDA’s request are four textured breast implants (Natrelle Saline-Filled Breast Implants, Natrelle Silicone-Filled Breast Implants, Natrelle Inspira Silicone-Filled breast Implants, and Natrelle 410 Highly Cohesive Anatomically Shaped Silicone-Filled Breast Implants) and two tissue expanders used prior to a breast implant (Natrelle 133 Plus Tissue Expander and the Natrelle 133 Tissue Expander with Suture Tabs).
FDA officials said they are considering recommendations for changes to the labeling of breast implant products, including a possible boxed warning and beefed up patient information.
“The recall of these textured implants is a big deal in protecting women from the potential risks of developing, and dying from, this rare type of aggressive lymphoma,” Joshua Brody, MD, a medical oncologist and director of the lymphoma immunotherapy program at Mount Sinai Medical Center in New York said in a statement. “While case reports have suggested a potential link between some types of breast implants and this disease – anaplastic lymphoma – for over 20 years, it has taken time to gain sufficient evidence to suggest, and understand, the causality. Some types of implants induce inflammation, which can both increase the chance of developing cancer, and also help to ‘hide’ developing cancers from the immune system. By preventing further use of these implants, the FDA is helping women to protect themselves from the medically serious and emotionally exhausting effects of these risks.”
Dr. Brody reported having no relevant disclosures.
Moderately high dietary riboflavin linked to fewer migraines
PHILADELPHIA – People with moderately high levels of riboflavin consumption from food – two to three times the recommended dietary allowance – had a significantly lower prevalence of a recent severe or migraine headache in a study of more than 3,600 younger U.S. adults.
Adults 20-50 years old who consumed 2.07-2.87 mg riboflavin (vitamin B2) in food a day based on a 24-hour recall questionnaire had an adjusted, statistically significant 27% reduced prevalence of a recent severe or migraine headache, compared with people in the lowest quartile of dietary riboflavin intake, 1.45 mg/day or less, Margaret Slavin, Ph.D., said at the annual meeting of the American Headache Society. Foods particularly high in riboflavin include eggs, milk, and meat.
Dietary riboflavin intakes greater than 2.87 mg/day were not linked to a difference in the prevalence of a recent history of severe or migraine headache, compared with lowest-quartile consumption. Additionally, riboflavin intake from supplements alone at any level of consumption also showed no statistically significant link with the prevalence of a recent, severe headache, said Dr. Slavin, a nutrition and food studies researcher at George Mason University in Fairfax, Va.
The “vast majority” of people in the study had a riboflavin intake that at least matched the U.S. recommended dietary allowance (RDA),1.3 mg/ day for men and 1.1 mg/day for women), “but it’s possible that people with migraine headaches need more riboflavin,” Dr. Slavin suggested. Professional societies in the United States (Neurology. 2012 Apr;78[17]: 1346-53) and Canada (Can J Neurol Sci. 2012 Mar;39[Suppl 2]S8-S28) have gone on record with some level of recommendation for a daily riboflavin supplement of 400 mg to prevent migraine headaches, she said.
A U.S. guideline that included riboflavin has been “retired” because of an issue unrelated to riboflavin, according to the Neurology website.
The new study ran data collected in the biennial National Health and Nutrition Examination Survey (NHANES), specifically the surveys from 2001-2002 and 2003-2004. The combined data included 5,528 adults 20-50 years old, and 3,634 with complete data and without an excluding condition such as pregnancy, diabetes, or menopause. Among the study participants 884 reported having “severe headaches or migraines,” during the 3 months preceding the survey and the remaining 2,750 people served as controls. People who reported recent severe headache or migraine overall had a significantly lower average amount of vitamin B2 in their diet than did the controls, but the two subgroups showed no significant differences in their levels of riboflavin intake from supplements, or from both diet and supplements combined.
The researchers calculated odds ratios for people having severe headaches or migraines relative to their riboflavin-intake quartile, and they adjusted the findings for age, sex, body mass index, and alcohol intake.
Further analysis that looked at total riboflavin intake, from both food and supplements, showed that the two middle quartiles for this metric, with a combined riboflavin intake of 1.6-3.8 mg/day, had a significantly reduced prevalence of recent severe or migraine headaches, compared with the lowest-intake quartile, with an odds ratio that roughly matched the dietary riboflavin analysis.
Dr. Slavin has received research funding from the Egg Nutrition Center, the Maryland Soybean Board, the McCormick Science Institute, and PepsiCo.
SOURCE: Slavin M. Headache. 2019 June;59[S1]:1-208, Abstract LBOR04.
PHILADELPHIA – People with moderately high levels of riboflavin consumption from food – two to three times the recommended dietary allowance – had a significantly lower prevalence of a recent severe or migraine headache in a study of more than 3,600 younger U.S. adults.
Adults 20-50 years old who consumed 2.07-2.87 mg riboflavin (vitamin B2) in food a day based on a 24-hour recall questionnaire had an adjusted, statistically significant 27% reduced prevalence of a recent severe or migraine headache, compared with people in the lowest quartile of dietary riboflavin intake, 1.45 mg/day or less, Margaret Slavin, Ph.D., said at the annual meeting of the American Headache Society. Foods particularly high in riboflavin include eggs, milk, and meat.
Dietary riboflavin intakes greater than 2.87 mg/day were not linked to a difference in the prevalence of a recent history of severe or migraine headache, compared with lowest-quartile consumption. Additionally, riboflavin intake from supplements alone at any level of consumption also showed no statistically significant link with the prevalence of a recent, severe headache, said Dr. Slavin, a nutrition and food studies researcher at George Mason University in Fairfax, Va.
The “vast majority” of people in the study had a riboflavin intake that at least matched the U.S. recommended dietary allowance (RDA),1.3 mg/ day for men and 1.1 mg/day for women), “but it’s possible that people with migraine headaches need more riboflavin,” Dr. Slavin suggested. Professional societies in the United States (Neurology. 2012 Apr;78[17]: 1346-53) and Canada (Can J Neurol Sci. 2012 Mar;39[Suppl 2]S8-S28) have gone on record with some level of recommendation for a daily riboflavin supplement of 400 mg to prevent migraine headaches, she said.
A U.S. guideline that included riboflavin has been “retired” because of an issue unrelated to riboflavin, according to the Neurology website.
The new study ran data collected in the biennial National Health and Nutrition Examination Survey (NHANES), specifically the surveys from 2001-2002 and 2003-2004. The combined data included 5,528 adults 20-50 years old, and 3,634 with complete data and without an excluding condition such as pregnancy, diabetes, or menopause. Among the study participants 884 reported having “severe headaches or migraines,” during the 3 months preceding the survey and the remaining 2,750 people served as controls. People who reported recent severe headache or migraine overall had a significantly lower average amount of vitamin B2 in their diet than did the controls, but the two subgroups showed no significant differences in their levels of riboflavin intake from supplements, or from both diet and supplements combined.
The researchers calculated odds ratios for people having severe headaches or migraines relative to their riboflavin-intake quartile, and they adjusted the findings for age, sex, body mass index, and alcohol intake.
Further analysis that looked at total riboflavin intake, from both food and supplements, showed that the two middle quartiles for this metric, with a combined riboflavin intake of 1.6-3.8 mg/day, had a significantly reduced prevalence of recent severe or migraine headaches, compared with the lowest-intake quartile, with an odds ratio that roughly matched the dietary riboflavin analysis.
Dr. Slavin has received research funding from the Egg Nutrition Center, the Maryland Soybean Board, the McCormick Science Institute, and PepsiCo.
SOURCE: Slavin M. Headache. 2019 June;59[S1]:1-208, Abstract LBOR04.
PHILADELPHIA – People with moderately high levels of riboflavin consumption from food – two to three times the recommended dietary allowance – had a significantly lower prevalence of a recent severe or migraine headache in a study of more than 3,600 younger U.S. adults.
Adults 20-50 years old who consumed 2.07-2.87 mg riboflavin (vitamin B2) in food a day based on a 24-hour recall questionnaire had an adjusted, statistically significant 27% reduced prevalence of a recent severe or migraine headache, compared with people in the lowest quartile of dietary riboflavin intake, 1.45 mg/day or less, Margaret Slavin, Ph.D., said at the annual meeting of the American Headache Society. Foods particularly high in riboflavin include eggs, milk, and meat.
Dietary riboflavin intakes greater than 2.87 mg/day were not linked to a difference in the prevalence of a recent history of severe or migraine headache, compared with lowest-quartile consumption. Additionally, riboflavin intake from supplements alone at any level of consumption also showed no statistically significant link with the prevalence of a recent, severe headache, said Dr. Slavin, a nutrition and food studies researcher at George Mason University in Fairfax, Va.
The “vast majority” of people in the study had a riboflavin intake that at least matched the U.S. recommended dietary allowance (RDA),1.3 mg/ day for men and 1.1 mg/day for women), “but it’s possible that people with migraine headaches need more riboflavin,” Dr. Slavin suggested. Professional societies in the United States (Neurology. 2012 Apr;78[17]: 1346-53) and Canada (Can J Neurol Sci. 2012 Mar;39[Suppl 2]S8-S28) have gone on record with some level of recommendation for a daily riboflavin supplement of 400 mg to prevent migraine headaches, she said.
A U.S. guideline that included riboflavin has been “retired” because of an issue unrelated to riboflavin, according to the Neurology website.
The new study ran data collected in the biennial National Health and Nutrition Examination Survey (NHANES), specifically the surveys from 2001-2002 and 2003-2004. The combined data included 5,528 adults 20-50 years old, and 3,634 with complete data and without an excluding condition such as pregnancy, diabetes, or menopause. Among the study participants 884 reported having “severe headaches or migraines,” during the 3 months preceding the survey and the remaining 2,750 people served as controls. People who reported recent severe headache or migraine overall had a significantly lower average amount of vitamin B2 in their diet than did the controls, but the two subgroups showed no significant differences in their levels of riboflavin intake from supplements, or from both diet and supplements combined.
The researchers calculated odds ratios for people having severe headaches or migraines relative to their riboflavin-intake quartile, and they adjusted the findings for age, sex, body mass index, and alcohol intake.
Further analysis that looked at total riboflavin intake, from both food and supplements, showed that the two middle quartiles for this metric, with a combined riboflavin intake of 1.6-3.8 mg/day, had a significantly reduced prevalence of recent severe or migraine headaches, compared with the lowest-intake quartile, with an odds ratio that roughly matched the dietary riboflavin analysis.
Dr. Slavin has received research funding from the Egg Nutrition Center, the Maryland Soybean Board, the McCormick Science Institute, and PepsiCo.
SOURCE: Slavin M. Headache. 2019 June;59[S1]:1-208, Abstract LBOR04.
REPORTING FROM AHS 2019
Key clinical point: Higher dietary riboflavin intake may reduce the risk for severe or migraine headaches.
Major finding: People with dietary riboflavin levels 2-3 times the RDA had a 27% lower prevalence of severe or migraine headaches compared with the lowest riboflavin quartile.
Study details: Review of NHANES data from 2001-2004 for 3,634 adults 20-50 years old.
Disclosures: Dr. Slavin has received research funding from the Egg Nutrition Center, the Maryland Soybean Board, the McCormick Science Institute, and PepsiCo.
Source: Slavin M. Headache. 2019 June;59[S1]:1-208, Abstract LBOR04.
Medication overuse prevalent among U.S. migraine patients
PHILADELPHIA – according to findings from an analysis of 16,789 people with migraine.
About 18% of the people identified with migraine in the study cohort reported a drug consumption pattern that met the prespecified definition of “medication overuse,” Todd J. Schwedt, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. Supplying each migraine patient with a “comprehensive treatment plan” along with “improved acute treatment options ... may help reduce the prevalence and associated burden of medication overuse,” said Dr. Schwedt, a professor of neurology at the Mayo Clinic in Phoenix. The analysis also showed that medication overuse (MO) significantly linked with several markers of worse clinical status.
If patients have “an effective preventive treatment that reduces headaches and migraine attacks then they will, in general, use less acute medications. Many people with migraine never even get diagnosed, and patients who qualify for preventive treatment never get it,” Dr. Schwedt noted in an interview. He described a comprehensive treatment plan as a management strategy that includes lifestyle modifications, a migraine-prevention agent, and the availability of an effective acute treatment for a patient to use when a migraine strikes along with clear instructions on how to appropriately self-administer the medication. Only a small fraction of U.S. migraine patients currently receive this complete package of care, he said.
The analysis he ran used data collected in the CaMEO (Chronic Migraine Epidemiology and Outcomes) study, which used an Internet-based survey to collect data from a representative 58,000-person sample of U.S. residents, which included 16,789 who met the applied migraine definition, with 91% having fewer than 15 headaches/month and the remaining 9% with a monthly headache average of 15 or more (Cephalagia. 2015 Jun;35[7]:563-78).
The researchers defined overuse of a single medication as use 15 times or more a month of an NSAID, aspirin, or acetaminophen, or use at least 10 times a month of a triptan, ergotamine, or opioid. They also had a prespecified definition of multidrug overuse that applied similar monthly thresholds. The patients averaged about 41 years old, three-quarters were women, and 85% were white. Patients identified with MO had a substantially higher rate of headaches per month: an average of nearly 12, compared with an average of about 4 per month among those without overuse. Almost two-thirds of the patients with MO reported having been formally diagnosed as having migraine headaches, compared with 41% of those without overuse.
Among the 13,749 patients (82%) on some headache medication, 67% were on a nonopioid analgesic, including 61% on an NSAID. MO among all people on nonopioid analgesics was 16%, and 12% among those who used NSAIDS. The most overused drug in this subgroup were combination analgesics, overused by 18% of those taking these drugs.
The drug class with the biggest MO rate was opioids, used by 12% of those on any medication and overused by 22% of those taking an opioid. Triptans were taken by 11%, with an MO rate of 11% among these users. Ergotamine was used by less than 1% of all patients, and those taking this drug tallied a 19% MO rate.
“Opioids were the class most often overused, more evidence that opioids should rarely if ever be used to treat migraine,” Dr. Schwedt said.
The analysis also showed that patients who had MO has multiple signs of worse clinical status. Patients with MO had a significantly higher rate of diagnosed depression, 54%, compared with 28% in those without MO; anxiety, 49% compared with 26%; migraine-associated disability, 73% compared with 32%; migraine-associated functional impairment (Migraine Interictal Burden Scale), 65% compared with 32%; and emergency department or urgent care use, 13% compared with 3%. All these between-group differences were statistically significant.
CaMEO was funded by Allergan. Dr. Schwedt has been a consultant to Allergan, and also to Alder, Amgen, Cipla, Dr. Reddy’s, Ipsen, Lilly, Novartis, and Teva. He has stock ownership in Aural Analytics, Nocira, and Second Opinion, and he has received research funding from Amgen.
SOURCE: Schwedt TJ et al. Headache. 2019 June;59[S1]:83-4, Abstract P92.
PHILADELPHIA – according to findings from an analysis of 16,789 people with migraine.
About 18% of the people identified with migraine in the study cohort reported a drug consumption pattern that met the prespecified definition of “medication overuse,” Todd J. Schwedt, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. Supplying each migraine patient with a “comprehensive treatment plan” along with “improved acute treatment options ... may help reduce the prevalence and associated burden of medication overuse,” said Dr. Schwedt, a professor of neurology at the Mayo Clinic in Phoenix. The analysis also showed that medication overuse (MO) significantly linked with several markers of worse clinical status.
If patients have “an effective preventive treatment that reduces headaches and migraine attacks then they will, in general, use less acute medications. Many people with migraine never even get diagnosed, and patients who qualify for preventive treatment never get it,” Dr. Schwedt noted in an interview. He described a comprehensive treatment plan as a management strategy that includes lifestyle modifications, a migraine-prevention agent, and the availability of an effective acute treatment for a patient to use when a migraine strikes along with clear instructions on how to appropriately self-administer the medication. Only a small fraction of U.S. migraine patients currently receive this complete package of care, he said.
The analysis he ran used data collected in the CaMEO (Chronic Migraine Epidemiology and Outcomes) study, which used an Internet-based survey to collect data from a representative 58,000-person sample of U.S. residents, which included 16,789 who met the applied migraine definition, with 91% having fewer than 15 headaches/month and the remaining 9% with a monthly headache average of 15 or more (Cephalagia. 2015 Jun;35[7]:563-78).
The researchers defined overuse of a single medication as use 15 times or more a month of an NSAID, aspirin, or acetaminophen, or use at least 10 times a month of a triptan, ergotamine, or opioid. They also had a prespecified definition of multidrug overuse that applied similar monthly thresholds. The patients averaged about 41 years old, three-quarters were women, and 85% were white. Patients identified with MO had a substantially higher rate of headaches per month: an average of nearly 12, compared with an average of about 4 per month among those without overuse. Almost two-thirds of the patients with MO reported having been formally diagnosed as having migraine headaches, compared with 41% of those without overuse.
Among the 13,749 patients (82%) on some headache medication, 67% were on a nonopioid analgesic, including 61% on an NSAID. MO among all people on nonopioid analgesics was 16%, and 12% among those who used NSAIDS. The most overused drug in this subgroup were combination analgesics, overused by 18% of those taking these drugs.
The drug class with the biggest MO rate was opioids, used by 12% of those on any medication and overused by 22% of those taking an opioid. Triptans were taken by 11%, with an MO rate of 11% among these users. Ergotamine was used by less than 1% of all patients, and those taking this drug tallied a 19% MO rate.
“Opioids were the class most often overused, more evidence that opioids should rarely if ever be used to treat migraine,” Dr. Schwedt said.
The analysis also showed that patients who had MO has multiple signs of worse clinical status. Patients with MO had a significantly higher rate of diagnosed depression, 54%, compared with 28% in those without MO; anxiety, 49% compared with 26%; migraine-associated disability, 73% compared with 32%; migraine-associated functional impairment (Migraine Interictal Burden Scale), 65% compared with 32%; and emergency department or urgent care use, 13% compared with 3%. All these between-group differences were statistically significant.
CaMEO was funded by Allergan. Dr. Schwedt has been a consultant to Allergan, and also to Alder, Amgen, Cipla, Dr. Reddy’s, Ipsen, Lilly, Novartis, and Teva. He has stock ownership in Aural Analytics, Nocira, and Second Opinion, and he has received research funding from Amgen.
SOURCE: Schwedt TJ et al. Headache. 2019 June;59[S1]:83-4, Abstract P92.
PHILADELPHIA – according to findings from an analysis of 16,789 people with migraine.
About 18% of the people identified with migraine in the study cohort reported a drug consumption pattern that met the prespecified definition of “medication overuse,” Todd J. Schwedt, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. Supplying each migraine patient with a “comprehensive treatment plan” along with “improved acute treatment options ... may help reduce the prevalence and associated burden of medication overuse,” said Dr. Schwedt, a professor of neurology at the Mayo Clinic in Phoenix. The analysis also showed that medication overuse (MO) significantly linked with several markers of worse clinical status.
If patients have “an effective preventive treatment that reduces headaches and migraine attacks then they will, in general, use less acute medications. Many people with migraine never even get diagnosed, and patients who qualify for preventive treatment never get it,” Dr. Schwedt noted in an interview. He described a comprehensive treatment plan as a management strategy that includes lifestyle modifications, a migraine-prevention agent, and the availability of an effective acute treatment for a patient to use when a migraine strikes along with clear instructions on how to appropriately self-administer the medication. Only a small fraction of U.S. migraine patients currently receive this complete package of care, he said.
The analysis he ran used data collected in the CaMEO (Chronic Migraine Epidemiology and Outcomes) study, which used an Internet-based survey to collect data from a representative 58,000-person sample of U.S. residents, which included 16,789 who met the applied migraine definition, with 91% having fewer than 15 headaches/month and the remaining 9% with a monthly headache average of 15 or more (Cephalagia. 2015 Jun;35[7]:563-78).
The researchers defined overuse of a single medication as use 15 times or more a month of an NSAID, aspirin, or acetaminophen, or use at least 10 times a month of a triptan, ergotamine, or opioid. They also had a prespecified definition of multidrug overuse that applied similar monthly thresholds. The patients averaged about 41 years old, three-quarters were women, and 85% were white. Patients identified with MO had a substantially higher rate of headaches per month: an average of nearly 12, compared with an average of about 4 per month among those without overuse. Almost two-thirds of the patients with MO reported having been formally diagnosed as having migraine headaches, compared with 41% of those without overuse.
Among the 13,749 patients (82%) on some headache medication, 67% were on a nonopioid analgesic, including 61% on an NSAID. MO among all people on nonopioid analgesics was 16%, and 12% among those who used NSAIDS. The most overused drug in this subgroup were combination analgesics, overused by 18% of those taking these drugs.
The drug class with the biggest MO rate was opioids, used by 12% of those on any medication and overused by 22% of those taking an opioid. Triptans were taken by 11%, with an MO rate of 11% among these users. Ergotamine was used by less than 1% of all patients, and those taking this drug tallied a 19% MO rate.
“Opioids were the class most often overused, more evidence that opioids should rarely if ever be used to treat migraine,” Dr. Schwedt said.
The analysis also showed that patients who had MO has multiple signs of worse clinical status. Patients with MO had a significantly higher rate of diagnosed depression, 54%, compared with 28% in those without MO; anxiety, 49% compared with 26%; migraine-associated disability, 73% compared with 32%; migraine-associated functional impairment (Migraine Interictal Burden Scale), 65% compared with 32%; and emergency department or urgent care use, 13% compared with 3%. All these between-group differences were statistically significant.
CaMEO was funded by Allergan. Dr. Schwedt has been a consultant to Allergan, and also to Alder, Amgen, Cipla, Dr. Reddy’s, Ipsen, Lilly, Novartis, and Teva. He has stock ownership in Aural Analytics, Nocira, and Second Opinion, and he has received research funding from Amgen.
SOURCE: Schwedt TJ et al. Headache. 2019 June;59[S1]:83-4, Abstract P92.
REPORTING FROM AHS 2019
Perioperative scripts for migraine abortive drugs linked with fewer pain readmissions
PHILADELPHIA – , according to an observational review of nearly 22,000 migraine patients from the Boston area.
While this statistically significant observational association must be viewed with caution, it provides compelling evidence for clinicians to prescribe a migraine abortive agent to migraineurs soon after surgery so that patients have these drugs handy if a migraine strikes, a possibility made likely by the stress and disruption of surgery, Katharina Platzbecker, MD, said at the annual meeting of the American Headache Society.
Postoperative migraine patients who received an abortive prescription specifically for a triptan or ergotamine showed an even stronger protective association, with an adjusted, statistically-significant 67% reduced rate of 30-day readmission for pain compared with the 50% of migraine patients who did not receive an abortive agent prescription after their surgery, said Dr. Platzbecker, a research fellow in the department of anesthesia, critical care, and pain medicine at Beth Israel Deaconess Medical Center in Boston. Only 8% of patients in the study received a triptan or ergotamine, with the vast majority of these patients getting a triptan.
The other types of abortive drugs prescribed perioperatively to migraine patients were NSAIDs or acetaminophen, received by 47% of the patients studied. The adjusted analysis showed that patients who received a prescription for one of these drugs had a statistically significant 35% reduced rate of 30-day readmission for pain. Patients who did not receive a prescription for a migraine abortive drug often got an opioid prescription, which went to 87% of the entire study population. Some patients received perioperative prescriptions for more than one drug. The analysis also showed that periopertive opioid prescriptions had no significant association with the 30-day rate of pain readmissions. In addition, prescription of any pain-reducing medication immediately prior to surgery as prophylaxis, which occurred in 17% of patients, had no significant association with the rate of 30-day postoperative pain readmission.
Despite the lack of clear causal evidence, clinicians should “definitely” be more aggressive in prescribing abortive treatments, especially triptans, to patients with a history of migraine who undergo surgery, Dr. Platzbecker said in an interview. These patients “are likely at risk for migraine [episodes] after surgery,”
Her study used data collected from nearly 25,000 patients with a history of a migraine billing diagnosis who underwent surgery and was a patient in either the Beth Israel or Partners (Massachusetts General Hospital and Brigham and Women’s Hospital) health systems during 2005-2017. Complete data that fulfilled the requirements of the study were available for 21,932 of these patients, of whom 11,011 (50%) received a perioperative prescription for an abortive drug and 10,921 (50%) did not. The prescribing occurred totally at the discretion of each patient’s physicians and surgeons. The researchers defined perioperative prescription as a billing entry for a drug anytime after surgery and within 30 days of hospital discharge or until readmission. The entire group studied averaged about 50 years old, more than 80% were women, and those who received an abortive treatment prescription generally had longer surgeries, more inpatient surgeries, and higher rates of various comorbidities. The adjusted statistical analysis took into account baseline differences like these.
Additional sensitivity analyses showed that perioperative prescriptions for abortive treatments also linked with significant reductions in all 30-day hospital readmissions, and with 30-day pain readmissions in patients who received surgery as inpatients as well as in those who were outpatients, and the association was specific to migraine patients. When Dr. Platzbecker expanded the group of patients she examined to more than 62,000 with any headache diagnosis the association between receiving a prescription for an abortive treatment and reduced 30-day pain readmissions became statistically insignificant.
Dr. Platzbecker and her associates previously reported results from an adjusted analysis showing that patients from the same database with a history of migraine who underwent surgery had an overall 42% increased rate of 30-day readmissions for pain compared with surgery patients who had no migraine history (Cephalagia. 2019 Feb;39[2]:286-95).
Dr. Platzbecker had no commercial disclosures.
[email protected]
On Twitter @mitchelzoler
This article was updated 7/16/19.
PHILADELPHIA – , according to an observational review of nearly 22,000 migraine patients from the Boston area.
While this statistically significant observational association must be viewed with caution, it provides compelling evidence for clinicians to prescribe a migraine abortive agent to migraineurs soon after surgery so that patients have these drugs handy if a migraine strikes, a possibility made likely by the stress and disruption of surgery, Katharina Platzbecker, MD, said at the annual meeting of the American Headache Society.
Postoperative migraine patients who received an abortive prescription specifically for a triptan or ergotamine showed an even stronger protective association, with an adjusted, statistically-significant 67% reduced rate of 30-day readmission for pain compared with the 50% of migraine patients who did not receive an abortive agent prescription after their surgery, said Dr. Platzbecker, a research fellow in the department of anesthesia, critical care, and pain medicine at Beth Israel Deaconess Medical Center in Boston. Only 8% of patients in the study received a triptan or ergotamine, with the vast majority of these patients getting a triptan.
The other types of abortive drugs prescribed perioperatively to migraine patients were NSAIDs or acetaminophen, received by 47% of the patients studied. The adjusted analysis showed that patients who received a prescription for one of these drugs had a statistically significant 35% reduced rate of 30-day readmission for pain. Patients who did not receive a prescription for a migraine abortive drug often got an opioid prescription, which went to 87% of the entire study population. Some patients received perioperative prescriptions for more than one drug. The analysis also showed that periopertive opioid prescriptions had no significant association with the 30-day rate of pain readmissions. In addition, prescription of any pain-reducing medication immediately prior to surgery as prophylaxis, which occurred in 17% of patients, had no significant association with the rate of 30-day postoperative pain readmission.
Despite the lack of clear causal evidence, clinicians should “definitely” be more aggressive in prescribing abortive treatments, especially triptans, to patients with a history of migraine who undergo surgery, Dr. Platzbecker said in an interview. These patients “are likely at risk for migraine [episodes] after surgery,”
Her study used data collected from nearly 25,000 patients with a history of a migraine billing diagnosis who underwent surgery and was a patient in either the Beth Israel or Partners (Massachusetts General Hospital and Brigham and Women’s Hospital) health systems during 2005-2017. Complete data that fulfilled the requirements of the study were available for 21,932 of these patients, of whom 11,011 (50%) received a perioperative prescription for an abortive drug and 10,921 (50%) did not. The prescribing occurred totally at the discretion of each patient’s physicians and surgeons. The researchers defined perioperative prescription as a billing entry for a drug anytime after surgery and within 30 days of hospital discharge or until readmission. The entire group studied averaged about 50 years old, more than 80% were women, and those who received an abortive treatment prescription generally had longer surgeries, more inpatient surgeries, and higher rates of various comorbidities. The adjusted statistical analysis took into account baseline differences like these.
Additional sensitivity analyses showed that perioperative prescriptions for abortive treatments also linked with significant reductions in all 30-day hospital readmissions, and with 30-day pain readmissions in patients who received surgery as inpatients as well as in those who were outpatients, and the association was specific to migraine patients. When Dr. Platzbecker expanded the group of patients she examined to more than 62,000 with any headache diagnosis the association between receiving a prescription for an abortive treatment and reduced 30-day pain readmissions became statistically insignificant.
Dr. Platzbecker and her associates previously reported results from an adjusted analysis showing that patients from the same database with a history of migraine who underwent surgery had an overall 42% increased rate of 30-day readmissions for pain compared with surgery patients who had no migraine history (Cephalagia. 2019 Feb;39[2]:286-95).
Dr. Platzbecker had no commercial disclosures.
[email protected]
On Twitter @mitchelzoler
This article was updated 7/16/19.
PHILADELPHIA – , according to an observational review of nearly 22,000 migraine patients from the Boston area.
While this statistically significant observational association must be viewed with caution, it provides compelling evidence for clinicians to prescribe a migraine abortive agent to migraineurs soon after surgery so that patients have these drugs handy if a migraine strikes, a possibility made likely by the stress and disruption of surgery, Katharina Platzbecker, MD, said at the annual meeting of the American Headache Society.
Postoperative migraine patients who received an abortive prescription specifically for a triptan or ergotamine showed an even stronger protective association, with an adjusted, statistically-significant 67% reduced rate of 30-day readmission for pain compared with the 50% of migraine patients who did not receive an abortive agent prescription after their surgery, said Dr. Platzbecker, a research fellow in the department of anesthesia, critical care, and pain medicine at Beth Israel Deaconess Medical Center in Boston. Only 8% of patients in the study received a triptan or ergotamine, with the vast majority of these patients getting a triptan.
The other types of abortive drugs prescribed perioperatively to migraine patients were NSAIDs or acetaminophen, received by 47% of the patients studied. The adjusted analysis showed that patients who received a prescription for one of these drugs had a statistically significant 35% reduced rate of 30-day readmission for pain. Patients who did not receive a prescription for a migraine abortive drug often got an opioid prescription, which went to 87% of the entire study population. Some patients received perioperative prescriptions for more than one drug. The analysis also showed that periopertive opioid prescriptions had no significant association with the 30-day rate of pain readmissions. In addition, prescription of any pain-reducing medication immediately prior to surgery as prophylaxis, which occurred in 17% of patients, had no significant association with the rate of 30-day postoperative pain readmission.
Despite the lack of clear causal evidence, clinicians should “definitely” be more aggressive in prescribing abortive treatments, especially triptans, to patients with a history of migraine who undergo surgery, Dr. Platzbecker said in an interview. These patients “are likely at risk for migraine [episodes] after surgery,”
Her study used data collected from nearly 25,000 patients with a history of a migraine billing diagnosis who underwent surgery and was a patient in either the Beth Israel or Partners (Massachusetts General Hospital and Brigham and Women’s Hospital) health systems during 2005-2017. Complete data that fulfilled the requirements of the study were available for 21,932 of these patients, of whom 11,011 (50%) received a perioperative prescription for an abortive drug and 10,921 (50%) did not. The prescribing occurred totally at the discretion of each patient’s physicians and surgeons. The researchers defined perioperative prescription as a billing entry for a drug anytime after surgery and within 30 days of hospital discharge or until readmission. The entire group studied averaged about 50 years old, more than 80% were women, and those who received an abortive treatment prescription generally had longer surgeries, more inpatient surgeries, and higher rates of various comorbidities. The adjusted statistical analysis took into account baseline differences like these.
Additional sensitivity analyses showed that perioperative prescriptions for abortive treatments also linked with significant reductions in all 30-day hospital readmissions, and with 30-day pain readmissions in patients who received surgery as inpatients as well as in those who were outpatients, and the association was specific to migraine patients. When Dr. Platzbecker expanded the group of patients she examined to more than 62,000 with any headache diagnosis the association between receiving a prescription for an abortive treatment and reduced 30-day pain readmissions became statistically insignificant.
Dr. Platzbecker and her associates previously reported results from an adjusted analysis showing that patients from the same database with a history of migraine who underwent surgery had an overall 42% increased rate of 30-day readmissions for pain compared with surgery patients who had no migraine history (Cephalagia. 2019 Feb;39[2]:286-95).
Dr. Platzbecker had no commercial disclosures.
[email protected]
On Twitter @mitchelzoler
This article was updated 7/16/19.
REPORTING FROM AHS 2019
Telemedicine migraine consults are as effective as in-office visits
PHILADELPHIA – in a single-center, randomized trial with 40 patients, the first reported randomized study of the impact of true telemedicine on mid-term migraine management.
“Telemedicine was viable and produced similar outcomes at 1 year in a highly disabled cohort,” Deborah I. Friedman, MD, said at the annual meeting of the American Headache Society. Many patients expressed high satisfaction with the approach. In addition to resulting in predictably shorter travel times for patients, it also linked with a cut in the consultation length by about a quarter, reported Dr. Friedman, a professor of neurology and chief of the division of headache medicine at UT Southwestern Medical Center in Dallas.
“There is a lot of opportunity for telemedicine, particularly in headache medicine because usually after the first visit we mostly just talk with patients with no further examinations, so it lends itself to telemedicine. It extends your reach.” Dr. Friedman said in a video interview. It is particularly attractive to patients who live a substantial distance from the clinic or find it hard to fit an office visit into their schedule, but some participants said they preferred the direct interaction of an office visit, she noted.
In addition to showing the efficacy of telemedicine in this setting, Dr. Friedman said that she hoped the findings may help pave the way for easier insurance payment for telemedicine consultations with migraineurs.
“One of the main reasons I did this study was to provide evidence to use for compensation for telemedicine visits. It will be good to have evidence in the medical literature that the outcomes are similar and that nothing is lost in patient care with telemedicine,” she said.
The study randomized 40 patients scheduled to see Dr. Friedman for the first time for a migraine consultation and to start treatment. After all patients had their initial office visit and examination, 22 of the patients entered the telemedicine arm and had follow-up consultations after 4-6 weeks, and after 3, 6, 9, and 12 months. The remaining 18 patients were randomized to receive these consultations in the office. Eighteen of the telemedicine patients and 12 of the in-office patients returned for a 12-month assessment. Patients averaged about 40 years old, they had actual or potential travel distances for in-office visits that in some cases exceeded 300 miles one way, and their Migraine Disability Assessment score averaged just above 40.
The telmedicine patients completed 93% of their visits compared with 88% of the in-office patients, a difference that was not statistically different. Migraine Disability Assessment scores improved by an average of 24 points in the telemedicine patients and by an average 19 points among the in-office controls, a difference that was not significant. The two groups also showed similar levels of treatment response for reductions in number of headache days and headache severity improvement. Average session length was 25 minutes with telemedicine and 34 minutes in office, a statistically significant difference that Dr. Friedman attributed to the interest by patients who have traveled long distances to see her to “get their money’s worth” from their visit.
Dr. Friedman highlighted the importance of having the visual aspect of a telemedicine consultation in addition to the conversation. For the trial the audio-visual link was via a standard laptop connection. Some patients assigned to telemedicine voiced regret over not being able to be examined, immediately start a new treatment, or receive drug samples. Dr. Friedman said that she couldn’t think of any migraine patients to whom she wouldn’t offer the option of telemedicine visits following an initial, in-person visit. But her use of telemedicine in routine practice is on hold right now as her institution, UT Southwestern, is still working out its consent and billing system, she said.
The study received partial funding from Merck. Dr. Friedman had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
SOURCE: Friedman DI. Headache. 2019 June;59[S1]:1-208, LBOR01.
PHILADELPHIA – in a single-center, randomized trial with 40 patients, the first reported randomized study of the impact of true telemedicine on mid-term migraine management.
“Telemedicine was viable and produced similar outcomes at 1 year in a highly disabled cohort,” Deborah I. Friedman, MD, said at the annual meeting of the American Headache Society. Many patients expressed high satisfaction with the approach. In addition to resulting in predictably shorter travel times for patients, it also linked with a cut in the consultation length by about a quarter, reported Dr. Friedman, a professor of neurology and chief of the division of headache medicine at UT Southwestern Medical Center in Dallas.
“There is a lot of opportunity for telemedicine, particularly in headache medicine because usually after the first visit we mostly just talk with patients with no further examinations, so it lends itself to telemedicine. It extends your reach.” Dr. Friedman said in a video interview. It is particularly attractive to patients who live a substantial distance from the clinic or find it hard to fit an office visit into their schedule, but some participants said they preferred the direct interaction of an office visit, she noted.
In addition to showing the efficacy of telemedicine in this setting, Dr. Friedman said that she hoped the findings may help pave the way for easier insurance payment for telemedicine consultations with migraineurs.
“One of the main reasons I did this study was to provide evidence to use for compensation for telemedicine visits. It will be good to have evidence in the medical literature that the outcomes are similar and that nothing is lost in patient care with telemedicine,” she said.
The study randomized 40 patients scheduled to see Dr. Friedman for the first time for a migraine consultation and to start treatment. After all patients had their initial office visit and examination, 22 of the patients entered the telemedicine arm and had follow-up consultations after 4-6 weeks, and after 3, 6, 9, and 12 months. The remaining 18 patients were randomized to receive these consultations in the office. Eighteen of the telemedicine patients and 12 of the in-office patients returned for a 12-month assessment. Patients averaged about 40 years old, they had actual or potential travel distances for in-office visits that in some cases exceeded 300 miles one way, and their Migraine Disability Assessment score averaged just above 40.
The telmedicine patients completed 93% of their visits compared with 88% of the in-office patients, a difference that was not statistically different. Migraine Disability Assessment scores improved by an average of 24 points in the telemedicine patients and by an average 19 points among the in-office controls, a difference that was not significant. The two groups also showed similar levels of treatment response for reductions in number of headache days and headache severity improvement. Average session length was 25 minutes with telemedicine and 34 minutes in office, a statistically significant difference that Dr. Friedman attributed to the interest by patients who have traveled long distances to see her to “get their money’s worth” from their visit.
Dr. Friedman highlighted the importance of having the visual aspect of a telemedicine consultation in addition to the conversation. For the trial the audio-visual link was via a standard laptop connection. Some patients assigned to telemedicine voiced regret over not being able to be examined, immediately start a new treatment, or receive drug samples. Dr. Friedman said that she couldn’t think of any migraine patients to whom she wouldn’t offer the option of telemedicine visits following an initial, in-person visit. But her use of telemedicine in routine practice is on hold right now as her institution, UT Southwestern, is still working out its consent and billing system, she said.
The study received partial funding from Merck. Dr. Friedman had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
SOURCE: Friedman DI. Headache. 2019 June;59[S1]:1-208, LBOR01.
PHILADELPHIA – in a single-center, randomized trial with 40 patients, the first reported randomized study of the impact of true telemedicine on mid-term migraine management.
“Telemedicine was viable and produced similar outcomes at 1 year in a highly disabled cohort,” Deborah I. Friedman, MD, said at the annual meeting of the American Headache Society. Many patients expressed high satisfaction with the approach. In addition to resulting in predictably shorter travel times for patients, it also linked with a cut in the consultation length by about a quarter, reported Dr. Friedman, a professor of neurology and chief of the division of headache medicine at UT Southwestern Medical Center in Dallas.
“There is a lot of opportunity for telemedicine, particularly in headache medicine because usually after the first visit we mostly just talk with patients with no further examinations, so it lends itself to telemedicine. It extends your reach.” Dr. Friedman said in a video interview. It is particularly attractive to patients who live a substantial distance from the clinic or find it hard to fit an office visit into their schedule, but some participants said they preferred the direct interaction of an office visit, she noted.
In addition to showing the efficacy of telemedicine in this setting, Dr. Friedman said that she hoped the findings may help pave the way for easier insurance payment for telemedicine consultations with migraineurs.
“One of the main reasons I did this study was to provide evidence to use for compensation for telemedicine visits. It will be good to have evidence in the medical literature that the outcomes are similar and that nothing is lost in patient care with telemedicine,” she said.
The study randomized 40 patients scheduled to see Dr. Friedman for the first time for a migraine consultation and to start treatment. After all patients had their initial office visit and examination, 22 of the patients entered the telemedicine arm and had follow-up consultations after 4-6 weeks, and after 3, 6, 9, and 12 months. The remaining 18 patients were randomized to receive these consultations in the office. Eighteen of the telemedicine patients and 12 of the in-office patients returned for a 12-month assessment. Patients averaged about 40 years old, they had actual or potential travel distances for in-office visits that in some cases exceeded 300 miles one way, and their Migraine Disability Assessment score averaged just above 40.
The telmedicine patients completed 93% of their visits compared with 88% of the in-office patients, a difference that was not statistically different. Migraine Disability Assessment scores improved by an average of 24 points in the telemedicine patients and by an average 19 points among the in-office controls, a difference that was not significant. The two groups also showed similar levels of treatment response for reductions in number of headache days and headache severity improvement. Average session length was 25 minutes with telemedicine and 34 minutes in office, a statistically significant difference that Dr. Friedman attributed to the interest by patients who have traveled long distances to see her to “get their money’s worth” from their visit.
Dr. Friedman highlighted the importance of having the visual aspect of a telemedicine consultation in addition to the conversation. For the trial the audio-visual link was via a standard laptop connection. Some patients assigned to telemedicine voiced regret over not being able to be examined, immediately start a new treatment, or receive drug samples. Dr. Friedman said that she couldn’t think of any migraine patients to whom she wouldn’t offer the option of telemedicine visits following an initial, in-person visit. But her use of telemedicine in routine practice is on hold right now as her institution, UT Southwestern, is still working out its consent and billing system, she said.
The study received partial funding from Merck. Dr. Friedman had no relevant disclosures.
[email protected]
On Twitter @mitchelzoler
SOURCE: Friedman DI. Headache. 2019 June;59[S1]:1-208, LBOR01.
REPORTING FROM AHS 2019
Migraine comorbidities rise with increased headache days
PHILADELPHIA – The more days per month a person reported experiencing migraine headaches the greater their prevalence of various comorbidities associated with migraine headaches, including insomnia, depression, anxiety, and gastric ulcer disease, according to results from a survey of more than 92,000 U.S. residents.
“Increasing monthly headache day [MHD] frequency was associated with an increased risk of other health conditions in people with migraine,” Richard B. Lipton, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. “The findings may be due to direct causality, reverse causality, shared risk factors, or detection bias.”
Additional analysis of the association with gastric ulcer disease (GUD) showed that it also linked with the number of days per month when a person with migraine used an NSAID. Migraineurs who self-reported having GUD averaged 10.5 days a month using an NSAID, compared with an average NSAID usage of just over 6 days a month among migraineurs without GUD, Dr. Lipton, a professor and vice-chair of neurology at Albert Einstein College of Medicine, New York, reported in a separate poster at the meeting.
The Migraine in America Symptoms and Treatment (MAST) study enrolled more than 90,000 U.S. residents starting in 2016. Using a validated diagnostic screening tool, the MAST researchers identified 15,133 of these people as having at least one day with a migraine headache during the 3 months prior to the survey and 77,453 who reported no migraine history (Headache. 2018 Oct;58[9]: 1408-26). The people with migraine averaged 43 years old, compared with an average of 52 years for those without migraine; 73% of the migraineurs were women.
Analysis of the prevalence of various self-reported, physician-diagnosed comorbidities showed a strong correlation between the relative odds of having a comorbidity and the self-reported number of MHDs. For example, the odds ratio for having insomnia, compared with the people without migraine, was nearly 200% among people reporting 1-4 MHDs, more than 300% higher among those reporting 5-9 MHDs, 500% higher with MHDs of 10-14, and nearly 700% higher among people reporting 20 or more MHDs. The researchers saw roughly similar patterns of rising comorbidity prevalence with higher numbers of MHDs for depression, anxiety, and GUD. The prevalence of a history of stroke or transient ischemic attack also increased with increasing numbers of MHDs but less steeply than for the other comorbidities. And while the prevalence of peripheral artery disease and epilepsy was consistently more than 100% greater among the migraineurs, compared with those with no recent migraine history, the prevalence of each of these two comorbidities showed no clear pattern of increasing prevalence as MHDs increased.
The analysis looked specifically at the relationship between GUD and NSAID use among people reporting migraine. Overall, the migraineurs had a greater than 200% increased prevalence of GUD than those without migraine. The odds ratio for GUD among migraineurs with 1-4 MHDs was 2.6, compared with those without migraine, and the odds ratio steadily rose with increasing MHDs to a peak of 490% higher among those who averaged 21 or more MHDs.
This link between the number of MHDs and prevalence of GUD may have some relationship to oral NSAID use, as overall NSAID use was higher among people with recent migraines than in those without migraines. However, the number of days per month of oral NSAID use appeared to plateau at an average of about 19 days once people reported having at least 10 MHDs, the researchers said. Even when people reported having more than twice as many MHDs their NSAID use remained at an average of about 19 days per month.
MAST was sponsored by Dr. Reddy’s Laboratories. Dr. Lipton had been a consultant to Dr. Reddy’s and to several other companies.
SOURCE: Lipton RB et al. Headache. 2019 June;59[S1]:1-208, P54.
PHILADELPHIA – The more days per month a person reported experiencing migraine headaches the greater their prevalence of various comorbidities associated with migraine headaches, including insomnia, depression, anxiety, and gastric ulcer disease, according to results from a survey of more than 92,000 U.S. residents.
“Increasing monthly headache day [MHD] frequency was associated with an increased risk of other health conditions in people with migraine,” Richard B. Lipton, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. “The findings may be due to direct causality, reverse causality, shared risk factors, or detection bias.”
Additional analysis of the association with gastric ulcer disease (GUD) showed that it also linked with the number of days per month when a person with migraine used an NSAID. Migraineurs who self-reported having GUD averaged 10.5 days a month using an NSAID, compared with an average NSAID usage of just over 6 days a month among migraineurs without GUD, Dr. Lipton, a professor and vice-chair of neurology at Albert Einstein College of Medicine, New York, reported in a separate poster at the meeting.
The Migraine in America Symptoms and Treatment (MAST) study enrolled more than 90,000 U.S. residents starting in 2016. Using a validated diagnostic screening tool, the MAST researchers identified 15,133 of these people as having at least one day with a migraine headache during the 3 months prior to the survey and 77,453 who reported no migraine history (Headache. 2018 Oct;58[9]: 1408-26). The people with migraine averaged 43 years old, compared with an average of 52 years for those without migraine; 73% of the migraineurs were women.
Analysis of the prevalence of various self-reported, physician-diagnosed comorbidities showed a strong correlation between the relative odds of having a comorbidity and the self-reported number of MHDs. For example, the odds ratio for having insomnia, compared with the people without migraine, was nearly 200% among people reporting 1-4 MHDs, more than 300% higher among those reporting 5-9 MHDs, 500% higher with MHDs of 10-14, and nearly 700% higher among people reporting 20 or more MHDs. The researchers saw roughly similar patterns of rising comorbidity prevalence with higher numbers of MHDs for depression, anxiety, and GUD. The prevalence of a history of stroke or transient ischemic attack also increased with increasing numbers of MHDs but less steeply than for the other comorbidities. And while the prevalence of peripheral artery disease and epilepsy was consistently more than 100% greater among the migraineurs, compared with those with no recent migraine history, the prevalence of each of these two comorbidities showed no clear pattern of increasing prevalence as MHDs increased.
The analysis looked specifically at the relationship between GUD and NSAID use among people reporting migraine. Overall, the migraineurs had a greater than 200% increased prevalence of GUD than those without migraine. The odds ratio for GUD among migraineurs with 1-4 MHDs was 2.6, compared with those without migraine, and the odds ratio steadily rose with increasing MHDs to a peak of 490% higher among those who averaged 21 or more MHDs.
This link between the number of MHDs and prevalence of GUD may have some relationship to oral NSAID use, as overall NSAID use was higher among people with recent migraines than in those without migraines. However, the number of days per month of oral NSAID use appeared to plateau at an average of about 19 days once people reported having at least 10 MHDs, the researchers said. Even when people reported having more than twice as many MHDs their NSAID use remained at an average of about 19 days per month.
MAST was sponsored by Dr. Reddy’s Laboratories. Dr. Lipton had been a consultant to Dr. Reddy’s and to several other companies.
SOURCE: Lipton RB et al. Headache. 2019 June;59[S1]:1-208, P54.
PHILADELPHIA – The more days per month a person reported experiencing migraine headaches the greater their prevalence of various comorbidities associated with migraine headaches, including insomnia, depression, anxiety, and gastric ulcer disease, according to results from a survey of more than 92,000 U.S. residents.
“Increasing monthly headache day [MHD] frequency was associated with an increased risk of other health conditions in people with migraine,” Richard B. Lipton, MD, and his associates reported in a poster at the annual meeting of the American Headache Society. “The findings may be due to direct causality, reverse causality, shared risk factors, or detection bias.”
Additional analysis of the association with gastric ulcer disease (GUD) showed that it also linked with the number of days per month when a person with migraine used an NSAID. Migraineurs who self-reported having GUD averaged 10.5 days a month using an NSAID, compared with an average NSAID usage of just over 6 days a month among migraineurs without GUD, Dr. Lipton, a professor and vice-chair of neurology at Albert Einstein College of Medicine, New York, reported in a separate poster at the meeting.
The Migraine in America Symptoms and Treatment (MAST) study enrolled more than 90,000 U.S. residents starting in 2016. Using a validated diagnostic screening tool, the MAST researchers identified 15,133 of these people as having at least one day with a migraine headache during the 3 months prior to the survey and 77,453 who reported no migraine history (Headache. 2018 Oct;58[9]: 1408-26). The people with migraine averaged 43 years old, compared with an average of 52 years for those without migraine; 73% of the migraineurs were women.
Analysis of the prevalence of various self-reported, physician-diagnosed comorbidities showed a strong correlation between the relative odds of having a comorbidity and the self-reported number of MHDs. For example, the odds ratio for having insomnia, compared with the people without migraine, was nearly 200% among people reporting 1-4 MHDs, more than 300% higher among those reporting 5-9 MHDs, 500% higher with MHDs of 10-14, and nearly 700% higher among people reporting 20 or more MHDs. The researchers saw roughly similar patterns of rising comorbidity prevalence with higher numbers of MHDs for depression, anxiety, and GUD. The prevalence of a history of stroke or transient ischemic attack also increased with increasing numbers of MHDs but less steeply than for the other comorbidities. And while the prevalence of peripheral artery disease and epilepsy was consistently more than 100% greater among the migraineurs, compared with those with no recent migraine history, the prevalence of each of these two comorbidities showed no clear pattern of increasing prevalence as MHDs increased.
The analysis looked specifically at the relationship between GUD and NSAID use among people reporting migraine. Overall, the migraineurs had a greater than 200% increased prevalence of GUD than those without migraine. The odds ratio for GUD among migraineurs with 1-4 MHDs was 2.6, compared with those without migraine, and the odds ratio steadily rose with increasing MHDs to a peak of 490% higher among those who averaged 21 or more MHDs.
This link between the number of MHDs and prevalence of GUD may have some relationship to oral NSAID use, as overall NSAID use was higher among people with recent migraines than in those without migraines. However, the number of days per month of oral NSAID use appeared to plateau at an average of about 19 days once people reported having at least 10 MHDs, the researchers said. Even when people reported having more than twice as many MHDs their NSAID use remained at an average of about 19 days per month.
MAST was sponsored by Dr. Reddy’s Laboratories. Dr. Lipton had been a consultant to Dr. Reddy’s and to several other companies.
SOURCE: Lipton RB et al. Headache. 2019 June;59[S1]:1-208, P54.
REPORTING FROM AHS 2019
Drug efficacy in phase 2 RA trials often missing in phase 3
MADRID – The efficacy results from new rheumatoid arthritis drugs tested in many phase 2 trials run over the past couple of decades have routinely overestimated the efficacy of many of the drugs tested when compared with how the same agents performed in subsequent phase 3 testing, according to an analysis of published results from 44 pairs of phase 2 and 3 trials.
Based on the percentage of rheumatoid arthritis (RA) patients who showed an American College of Rheumatology 20% improvement (ACR20) in their joint symptoms, the 44 phase 2 trials overestimated efficacy by an average of 39% when compared with the ACR20 responses seen in paired phase 3 trials, Andreas Kerschbaumer, MD, said at the European Congress of Rheumatology. The ACR50 results overstated efficacy by an average of 34% when compared with phase 3 results for the same drugs, and the ACR70 endpoint showed drug efficacy that averaged 39% better during phase 2 studies than it did in the phase 3 trials. All three between-group differences were statistically significant, said Dr. Kerschbaumer, a rheumatologist at the Medical University of Vienna.
“Active treatment arms of phase 2 studies systematically overestimated efficacy when compared with subsequent phase 3 studies,” he said.
“Many researchers had already seen this, and realized that phase 2 trials often overestimated [efficacy], but no one has ever shown this systematically,” Dr. Kerschbaumer said in an interview. The same problem also appears to affect trials of oncology drugs, he noted, but a unique feature of RA studies allowed him and his colleagues to examine the ubiquity and persistence of this phase 2 bias in rheumatology trials over time: ongoing reliance during more than 2 decades of experience on the ACR20 response as the primary endpoint of RA drug trials. Even with this advantage, which allowed inclusion of 44 pairs of studies, “it was very surprising to find a statistically significant effect in the meta-analysis,” he said.
He and his associates also ran a further analysis that looked for measured parameters that showed significant correlation with mismatch of the phase 2 and 3 results, and this identified two apparently causal factors: having a low number of swollen and tender joints as an inclusion criterion for patients and using a 28-joint count rather than a 66-joint count for assessing disease activity during the study. The analysis lacked enough information to provide clear evidence on why these two aspects of patient assessment could lead to misleading phase 2 results, but Dr. Kerschbaumer believed the findings were clear enough to influence future trial design.
Going forward, trialists “should be very careful of how you include patients [in studies]. This is what our study shows. And they should not use 28 joints but 66. The higher the number of swollen and tender joints detected for study inclusion, the less the possibility to overestimate [efficacy]. It’s easier to achieve ACR20 when you look at fewer joints.”
Until now, companies that sponsor drug trials had an incentive to use a lower minimum number of swollen and tender joints for enrolled patients because it made enrollment easier, he noted. The downside, in addition to overstating efficacy at the phase 2 stage, is subjecting patients to treatments in phase 3 trials with a reduced likelihood for success.
Dr. Kerschbaumer offered two examples of drugs that showed promising RA efficacy based on ACR20 responses in phase 2 trial results that were followed by neutral phase 3 trial outcomes. One episode involved tabalumab (Ann Rheum Dis. 2015 Aug;74[8]:1567-70), and a second was a trial of fostamatinib (Arthritis Rheumatol. 2014 Dec;66[12]:3255-64).
The systematic review he led identified 44 study pairs run since the late 1990s that met all the study criteria, which covered 19 different drugs tested in more than 17,000 RA patients.
What the results showed was “just an association, so we must be careful not to overstate the results, but we saw something that may explain what people have seen [anecdotally] over the past 20 years,” he said. “Some people get very excited by phase 2 results, but we need to be careful about interpreting these outcomes.” Validation of the finding would require analysis of patient-level data, something that would be hard to obtain for a large number of phase 2 and 3 trials, Dr. Kerschbaumer noted.
Dr. Kerschbaumer has been a speaker on behalf of Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, and Pfizer.
SOURCE: Kerschbaumer A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):191-2. Abstract OP0229, doi: 10.1136/annrheumdis-2019-eular.5161.
MADRID – The efficacy results from new rheumatoid arthritis drugs tested in many phase 2 trials run over the past couple of decades have routinely overestimated the efficacy of many of the drugs tested when compared with how the same agents performed in subsequent phase 3 testing, according to an analysis of published results from 44 pairs of phase 2 and 3 trials.
Based on the percentage of rheumatoid arthritis (RA) patients who showed an American College of Rheumatology 20% improvement (ACR20) in their joint symptoms, the 44 phase 2 trials overestimated efficacy by an average of 39% when compared with the ACR20 responses seen in paired phase 3 trials, Andreas Kerschbaumer, MD, said at the European Congress of Rheumatology. The ACR50 results overstated efficacy by an average of 34% when compared with phase 3 results for the same drugs, and the ACR70 endpoint showed drug efficacy that averaged 39% better during phase 2 studies than it did in the phase 3 trials. All three between-group differences were statistically significant, said Dr. Kerschbaumer, a rheumatologist at the Medical University of Vienna.
“Active treatment arms of phase 2 studies systematically overestimated efficacy when compared with subsequent phase 3 studies,” he said.
“Many researchers had already seen this, and realized that phase 2 trials often overestimated [efficacy], but no one has ever shown this systematically,” Dr. Kerschbaumer said in an interview. The same problem also appears to affect trials of oncology drugs, he noted, but a unique feature of RA studies allowed him and his colleagues to examine the ubiquity and persistence of this phase 2 bias in rheumatology trials over time: ongoing reliance during more than 2 decades of experience on the ACR20 response as the primary endpoint of RA drug trials. Even with this advantage, which allowed inclusion of 44 pairs of studies, “it was very surprising to find a statistically significant effect in the meta-analysis,” he said.
He and his associates also ran a further analysis that looked for measured parameters that showed significant correlation with mismatch of the phase 2 and 3 results, and this identified two apparently causal factors: having a low number of swollen and tender joints as an inclusion criterion for patients and using a 28-joint count rather than a 66-joint count for assessing disease activity during the study. The analysis lacked enough information to provide clear evidence on why these two aspects of patient assessment could lead to misleading phase 2 results, but Dr. Kerschbaumer believed the findings were clear enough to influence future trial design.
Going forward, trialists “should be very careful of how you include patients [in studies]. This is what our study shows. And they should not use 28 joints but 66. The higher the number of swollen and tender joints detected for study inclusion, the less the possibility to overestimate [efficacy]. It’s easier to achieve ACR20 when you look at fewer joints.”
Until now, companies that sponsor drug trials had an incentive to use a lower minimum number of swollen and tender joints for enrolled patients because it made enrollment easier, he noted. The downside, in addition to overstating efficacy at the phase 2 stage, is subjecting patients to treatments in phase 3 trials with a reduced likelihood for success.
Dr. Kerschbaumer offered two examples of drugs that showed promising RA efficacy based on ACR20 responses in phase 2 trial results that were followed by neutral phase 3 trial outcomes. One episode involved tabalumab (Ann Rheum Dis. 2015 Aug;74[8]:1567-70), and a second was a trial of fostamatinib (Arthritis Rheumatol. 2014 Dec;66[12]:3255-64).
The systematic review he led identified 44 study pairs run since the late 1990s that met all the study criteria, which covered 19 different drugs tested in more than 17,000 RA patients.
What the results showed was “just an association, so we must be careful not to overstate the results, but we saw something that may explain what people have seen [anecdotally] over the past 20 years,” he said. “Some people get very excited by phase 2 results, but we need to be careful about interpreting these outcomes.” Validation of the finding would require analysis of patient-level data, something that would be hard to obtain for a large number of phase 2 and 3 trials, Dr. Kerschbaumer noted.
Dr. Kerschbaumer has been a speaker on behalf of Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, and Pfizer.
SOURCE: Kerschbaumer A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):191-2. Abstract OP0229, doi: 10.1136/annrheumdis-2019-eular.5161.
MADRID – The efficacy results from new rheumatoid arthritis drugs tested in many phase 2 trials run over the past couple of decades have routinely overestimated the efficacy of many of the drugs tested when compared with how the same agents performed in subsequent phase 3 testing, according to an analysis of published results from 44 pairs of phase 2 and 3 trials.
Based on the percentage of rheumatoid arthritis (RA) patients who showed an American College of Rheumatology 20% improvement (ACR20) in their joint symptoms, the 44 phase 2 trials overestimated efficacy by an average of 39% when compared with the ACR20 responses seen in paired phase 3 trials, Andreas Kerschbaumer, MD, said at the European Congress of Rheumatology. The ACR50 results overstated efficacy by an average of 34% when compared with phase 3 results for the same drugs, and the ACR70 endpoint showed drug efficacy that averaged 39% better during phase 2 studies than it did in the phase 3 trials. All three between-group differences were statistically significant, said Dr. Kerschbaumer, a rheumatologist at the Medical University of Vienna.
“Active treatment arms of phase 2 studies systematically overestimated efficacy when compared with subsequent phase 3 studies,” he said.
“Many researchers had already seen this, and realized that phase 2 trials often overestimated [efficacy], but no one has ever shown this systematically,” Dr. Kerschbaumer said in an interview. The same problem also appears to affect trials of oncology drugs, he noted, but a unique feature of RA studies allowed him and his colleagues to examine the ubiquity and persistence of this phase 2 bias in rheumatology trials over time: ongoing reliance during more than 2 decades of experience on the ACR20 response as the primary endpoint of RA drug trials. Even with this advantage, which allowed inclusion of 44 pairs of studies, “it was very surprising to find a statistically significant effect in the meta-analysis,” he said.
He and his associates also ran a further analysis that looked for measured parameters that showed significant correlation with mismatch of the phase 2 and 3 results, and this identified two apparently causal factors: having a low number of swollen and tender joints as an inclusion criterion for patients and using a 28-joint count rather than a 66-joint count for assessing disease activity during the study. The analysis lacked enough information to provide clear evidence on why these two aspects of patient assessment could lead to misleading phase 2 results, but Dr. Kerschbaumer believed the findings were clear enough to influence future trial design.
Going forward, trialists “should be very careful of how you include patients [in studies]. This is what our study shows. And they should not use 28 joints but 66. The higher the number of swollen and tender joints detected for study inclusion, the less the possibility to overestimate [efficacy]. It’s easier to achieve ACR20 when you look at fewer joints.”
Until now, companies that sponsor drug trials had an incentive to use a lower minimum number of swollen and tender joints for enrolled patients because it made enrollment easier, he noted. The downside, in addition to overstating efficacy at the phase 2 stage, is subjecting patients to treatments in phase 3 trials with a reduced likelihood for success.
Dr. Kerschbaumer offered two examples of drugs that showed promising RA efficacy based on ACR20 responses in phase 2 trial results that were followed by neutral phase 3 trial outcomes. One episode involved tabalumab (Ann Rheum Dis. 2015 Aug;74[8]:1567-70), and a second was a trial of fostamatinib (Arthritis Rheumatol. 2014 Dec;66[12]:3255-64).
The systematic review he led identified 44 study pairs run since the late 1990s that met all the study criteria, which covered 19 different drugs tested in more than 17,000 RA patients.
What the results showed was “just an association, so we must be careful not to overstate the results, but we saw something that may explain what people have seen [anecdotally] over the past 20 years,” he said. “Some people get very excited by phase 2 results, but we need to be careful about interpreting these outcomes.” Validation of the finding would require analysis of patient-level data, something that would be hard to obtain for a large number of phase 2 and 3 trials, Dr. Kerschbaumer noted.
Dr. Kerschbaumer has been a speaker on behalf of Bristol-Myers Squibb, Celgene, Merck Sharp & Dohme, and Pfizer.
SOURCE: Kerschbaumer A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):191-2. Abstract OP0229, doi: 10.1136/annrheumdis-2019-eular.5161.
REPORTING FROM EULAR 2019 CONGRESS
FDA warning letters fall on Trump’s watch
according to findings from an analysis of public records sponsored by Science magazine and published July 2.
From Jan. 20, 2017, (President Trump’s inauguration day) through May 22, 2019, FDA sent out 1,033 warning letters, compared with 1,532 warning letters sent during the 28 months ending just before the inauguration, a drop of 33%, wrote Charles Piller, an investigative journalist on the Science staff (Science. 2019 Jul 2. doi: 10.1126/science.aay5859). Also during January 2017–May 2019, “official action indicated” reports, described by Mr. Piller as a frequent precursor to warning letters, fell by 45%, from 1,879 during the final 28 months of the Obama administration to 1,040 during the first 28 months of the Trump administration. The incidence of an injunction, characterized by Mr. Piller as a ”more forceful” step than a warning letter, was 35 during the 28 months before Donald Trump became president and 26 during the 28 months after, a relative 26% decline.
More detailed numbers in the report included a 33% drop in warning letters from the FDA center that deals with tobacco products, a 37% drop in warning letters from the center that deals with food safety, and a 72% fall in letters sent from the Center for Devices & Radiological Health. However the FDA Center for Drug Evaluation & Research sent 62% more warning letters (188) during the first 28 months after Donald Trump became president, compared with the final 28 months under President Obama, when it sent 116 warning letters. A year-by-year analysis that started in 2009 showed that warning letters peaked at about 800 per year during both 2011 and 2012, and then showed a steady decline during all subsequent years, falling to a rate during the first months of 2019 that projected to an annualized rate of 385 total warning letters sent by the end of this year.
In response to publication of these findings, FDA Media Relations Director Angela Stark said “the way the data are presented in the story does not accurately reflect FDA’s overarching work to protect the public health. While one publicly visible measure of FDA action, it’s important to understand that warning letters are just one action the FDA takes to seek compliance. The FDA has several tools at its disposal to work with a company to ensure compliance, such as through regulatory meetings with companies; untitled letters; follow-up inspections; and other regulatory and compliance measures depending on the situation, and we often do much of this behind the scenes in the interest of patient safety. Our use of any one enforcement tool may fluctuate year to year based on a number of factors, including the FDA’s assessment of the violations uncovered during the course of inspections, along with additional product-monitoring efforts.”
Ms. Stark also noted that, in some FDA centers, warning letters may have decreased “because the FDA has increased its interactions with industry to resolve issues, which often achieves more timely and effective corrective action.”
She also highlighted 1,300 warning letter and monetary penalty complaints sent to retailers since September 2018 over illegal sales of e-cigarettes to minors, “tens of thousands” of warning letters sent to tobacco retailers since the start of 2017 over other tobacco-related issues, and actions against stem-cell clinics that have marketed unapproved treatments.
[email protected]
SOURCE: Piller C. Science. 2019 Jul 2. doi: 10.1126/science.aay5859)
according to findings from an analysis of public records sponsored by Science magazine and published July 2.
From Jan. 20, 2017, (President Trump’s inauguration day) through May 22, 2019, FDA sent out 1,033 warning letters, compared with 1,532 warning letters sent during the 28 months ending just before the inauguration, a drop of 33%, wrote Charles Piller, an investigative journalist on the Science staff (Science. 2019 Jul 2. doi: 10.1126/science.aay5859). Also during January 2017–May 2019, “official action indicated” reports, described by Mr. Piller as a frequent precursor to warning letters, fell by 45%, from 1,879 during the final 28 months of the Obama administration to 1,040 during the first 28 months of the Trump administration. The incidence of an injunction, characterized by Mr. Piller as a ”more forceful” step than a warning letter, was 35 during the 28 months before Donald Trump became president and 26 during the 28 months after, a relative 26% decline.
More detailed numbers in the report included a 33% drop in warning letters from the FDA center that deals with tobacco products, a 37% drop in warning letters from the center that deals with food safety, and a 72% fall in letters sent from the Center for Devices & Radiological Health. However the FDA Center for Drug Evaluation & Research sent 62% more warning letters (188) during the first 28 months after Donald Trump became president, compared with the final 28 months under President Obama, when it sent 116 warning letters. A year-by-year analysis that started in 2009 showed that warning letters peaked at about 800 per year during both 2011 and 2012, and then showed a steady decline during all subsequent years, falling to a rate during the first months of 2019 that projected to an annualized rate of 385 total warning letters sent by the end of this year.
In response to publication of these findings, FDA Media Relations Director Angela Stark said “the way the data are presented in the story does not accurately reflect FDA’s overarching work to protect the public health. While one publicly visible measure of FDA action, it’s important to understand that warning letters are just one action the FDA takes to seek compliance. The FDA has several tools at its disposal to work with a company to ensure compliance, such as through regulatory meetings with companies; untitled letters; follow-up inspections; and other regulatory and compliance measures depending on the situation, and we often do much of this behind the scenes in the interest of patient safety. Our use of any one enforcement tool may fluctuate year to year based on a number of factors, including the FDA’s assessment of the violations uncovered during the course of inspections, along with additional product-monitoring efforts.”
Ms. Stark also noted that, in some FDA centers, warning letters may have decreased “because the FDA has increased its interactions with industry to resolve issues, which often achieves more timely and effective corrective action.”
She also highlighted 1,300 warning letter and monetary penalty complaints sent to retailers since September 2018 over illegal sales of e-cigarettes to minors, “tens of thousands” of warning letters sent to tobacco retailers since the start of 2017 over other tobacco-related issues, and actions against stem-cell clinics that have marketed unapproved treatments.
[email protected]
SOURCE: Piller C. Science. 2019 Jul 2. doi: 10.1126/science.aay5859)
according to findings from an analysis of public records sponsored by Science magazine and published July 2.
From Jan. 20, 2017, (President Trump’s inauguration day) through May 22, 2019, FDA sent out 1,033 warning letters, compared with 1,532 warning letters sent during the 28 months ending just before the inauguration, a drop of 33%, wrote Charles Piller, an investigative journalist on the Science staff (Science. 2019 Jul 2. doi: 10.1126/science.aay5859). Also during January 2017–May 2019, “official action indicated” reports, described by Mr. Piller as a frequent precursor to warning letters, fell by 45%, from 1,879 during the final 28 months of the Obama administration to 1,040 during the first 28 months of the Trump administration. The incidence of an injunction, characterized by Mr. Piller as a ”more forceful” step than a warning letter, was 35 during the 28 months before Donald Trump became president and 26 during the 28 months after, a relative 26% decline.
More detailed numbers in the report included a 33% drop in warning letters from the FDA center that deals with tobacco products, a 37% drop in warning letters from the center that deals with food safety, and a 72% fall in letters sent from the Center for Devices & Radiological Health. However the FDA Center for Drug Evaluation & Research sent 62% more warning letters (188) during the first 28 months after Donald Trump became president, compared with the final 28 months under President Obama, when it sent 116 warning letters. A year-by-year analysis that started in 2009 showed that warning letters peaked at about 800 per year during both 2011 and 2012, and then showed a steady decline during all subsequent years, falling to a rate during the first months of 2019 that projected to an annualized rate of 385 total warning letters sent by the end of this year.
In response to publication of these findings, FDA Media Relations Director Angela Stark said “the way the data are presented in the story does not accurately reflect FDA’s overarching work to protect the public health. While one publicly visible measure of FDA action, it’s important to understand that warning letters are just one action the FDA takes to seek compliance. The FDA has several tools at its disposal to work with a company to ensure compliance, such as through regulatory meetings with companies; untitled letters; follow-up inspections; and other regulatory and compliance measures depending on the situation, and we often do much of this behind the scenes in the interest of patient safety. Our use of any one enforcement tool may fluctuate year to year based on a number of factors, including the FDA’s assessment of the violations uncovered during the course of inspections, along with additional product-monitoring efforts.”
Ms. Stark also noted that, in some FDA centers, warning letters may have decreased “because the FDA has increased its interactions with industry to resolve issues, which often achieves more timely and effective corrective action.”
She also highlighted 1,300 warning letter and monetary penalty complaints sent to retailers since September 2018 over illegal sales of e-cigarettes to minors, “tens of thousands” of warning letters sent to tobacco retailers since the start of 2017 over other tobacco-related issues, and actions against stem-cell clinics that have marketed unapproved treatments.
[email protected]
SOURCE: Piller C. Science. 2019 Jul 2. doi: 10.1126/science.aay5859)
FROM SCIENCE
EULAR keeps csDMARDs as top PsA drugs
MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.
For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.
The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).
The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.
The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).
This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.
“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.
In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.
The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.
Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”
Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”
Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.
When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.
Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.
MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.
For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.
The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).
The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.
The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).
This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.
“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.
In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.
The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.
Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”
Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”
Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.
When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.
Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.
MADRID – The draft revision of the European League Against Rheumatism’s recommendations for managing psoriatic arthritis sticks with the group’s already-existing conviction that psoriatic arthritis treatment best starts with an NSAID, and if that fails follow with a conventional synthetic antirheumatic drug such as methotrexate, a position in stark contrast with the 2018 recommendation from the American College of Rheumatology to first treat with a tumor necrosis factor (TNF) inhibitor.
For patients with psoriatic arthritis (PsA) manifesting with polyarthritis, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) “should be first,” and should “start rapidly” if brief, initial treatment with an NSAID proves inadequate, Laure Gossec, MD, PhD, said while presenting a draft version of an update to the PsA management recommendations from EULAR at the European Congress of Rheumatology.
The EULAR recommendations-revision panel had about the same advice for managing PsA patients with oligoarthritis, monoarthritis, or peripheral arthritis. For oligo- and monoarthritis, “consider a csDMARD after failing NSAIDS, but also consider the patient’s prognostic factors,” like structural damage, and dactylitis. For PsA patients with peripheral arthritis, “it still makes sense to keep csDMARDs as the first line treatment,” said Dr. Gossec, professor of rheumatology at Pitie-Salpétriere Hospital and Sorbonne University, Paris. Once published, the revision will replace existing EULAR recommendations from 2015 (Ann Rheum Dis. 2016 Mar;75[3]:499-510).
The list of csDMARDs she cited included not just methotrexate, still the top csDMARD, but also sulfasalazine and leflunomide as alternatives, she noted, with methotrexate also the preferred csDMARD for patients with skin involvement. When a PsA patient fails at least one csDMARD, then switching to a biologic DMARD is recommended. For a patient with skin involvement, a drug that targets interleukin-17 or IL-12 and -23 is preferred. If skin involvement is not a major issue, then treatment with a TNF inhibitor is equally valid, she said.
The 2018 PsA management guideline from the American College of Rheumatology (ACR) proposed a strikingly different sequence, endorsing initial treatment with a TNF inhibitor first over all other options, including methotrexate and other “oral small molecules” (the ACR term for csDMARD), and also including NSAIDs (Arthritis Rheumatol. 2019 Jan;71[1]:5-32).
This schism between EULAR and the ACR could be seen as predictable, given the different constraints the two societies have set for themselves.
“EULAR recommendations take into account drug costs; the ACR guideline is supposed to be agnostic to costs,” explained Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle and a member of the ACR panel that wrote the 2018 PsA guideline.
In fact it was a study Dr. Mease recently led and reported results from that provided the most recent and perhaps best assessment of a TNF inhibitor, compared with methotrexate, as initial treatment for PsA, with findings that suggest that, although the advice from the two societies may sharply differ, the viewpoints of both groups are evidence based.
The SEAM-PsA (Study of Etanercept and Methotrexate in Subjects with Psoriatic Arthritis) trial randomized 851 PsA patients receiving their first treatment to methotrexate only, the TNF inhibitor etanercept (Enbrel) only, or both drugs. The study’s two coprimary outcomes, the ACR 20 and minimal disease activity responses after 24 weeks, showed that etanercept monotherapy produced these responses in 61% and 36% of patients, respectively, while methotrexate monotherapy produced response rates of 51% and 23%, respectively. Both these differences between etanercept monotherapy and methotrexate monotherapy were statistically significant. Combining methotrexate with etanercept did not produce a significant improvement over etanercept alone.
Interpreting the meaning of this finding for clinical practice “depends on the lens you look through,” Dr. Mease said in an interview. “A lot of patients respond to methotrexate, which is good when treatment resources are challenged. But when there is no resource challenge, the data support going straight to a TNF inhibitor.”
Dr. Gossec confirmed the importance of the SEAM-PsA findings in the writing panel’s decision during discussion of the draft, replying to a question about consideration of the study’s findings. “We carefully looked at the SEAM-PsA trial results, which provide some of the only data we have on methotrexate” for PsA. “We felt that the results were in favor of methotrexate’s efficacy, and therefore did not go against our proposal to keep a graduated approach starting with a csDMARD.”
Patients who fail to receive adequate relief from a csDMARD could then try a biologic DMARD – a TNF inhibitor, IL-17 inhibitor, or IL-12/23 inhibitor, Dr. Gossec said. When skin involvement is minimal, any of these options are possible, she said. If skin involvement is significant, the panel recommended preferentially using an IL-17 or IL-12/23 inhibitor based on head-to-head trials in patients with psoriasis, she said.
When a biologic DMARD is not appropriate or fails, another option is to then try a targeted synthetic DMARD, such as a Janus kinase inhibitor. When none of these options are appropriate, or they all fail, another option for patients with mild oligo- or monoarthritis or in patients with limited skin involvement is apremilast (Otezla), a phosphodiesterase-4 inhibitor. The draft recommendations also advise clinicians to be sure to distinguish fibromyalgia pain from enthesitis involvement, and they introduce the possibility of, with “great caution,” tapering down DMARD treatment in PsA patients who show sustained remission.
Dr. Gossec and Dr. Mease have both been consultants to and received honoraria from several companies. SEAM-PsA was sponsored by Amgen, the company that markets Enbrel.
REPORTING FROM EULAR 2019 CONGRESS
Infections linked with transition to psoriatic arthritis
MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.
The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.
The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.
The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.
Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.
The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.
During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.
The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).
This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.
All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.
SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.
MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.
The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.
The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.
The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.
Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.
The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.
During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.
The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).
This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.
All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.
SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.
MADRID – Several novel risk associations with psoriasis progression were found to differ by sex, and collectively appeared to implicate infections and the “stress response” as a trigger of psoriatic arthritis.
The findings come from a risk factor analysis of a U.S. claims database of more than 200,000 adults with psoriasis including more than 4,000 patients who progressed to psoriatic arthritis during nearly 6 years of follow-up.
The new analysis confirmed several previously described risk associations linked with progression to psoriatic arthritis (PsA) that have roughly equal impact on both women and men: fatigue, obesity, and depression, Alexis Ogdie, MD, said at the European Congress of Rheumatology. The new findings also showed several novel, sex-specific associations. In women, these associations included salmonella infection, sepsis, and uveitis; in men, they included gangrene, encephalitis, and hidradenitis suppurativa.
The links with various infections were generally rare; they showed strong nominal associations in multivariate analyses but with wide confidence limits. The findings suggest that events that induce major stress responses, such as infections, often preceded the progression of psoriasis to a diagnosis of PsA, said Dr. Ogdie, director of the psoriatic arthritis clinic at the University of Pennsylvania in Philadelphia. Other, noninfectious clinical features that significantly linked with PsA development but at a lower magnitude included anemia and diabetes in women, and irritable bowel syndrome and venous thromboembolism in men.
Dr. Ogdie cautioned that the findings were preliminary and need confirmation in different data sets, as well as in additional subgroup analyses of the data used in the current analysis, taken from the electronic medical records of 215,386 U.S. residents diagnosed with psoriasis in the Optum medical-claims database for 2006-2017.
The analysis focused on patients who received a second diagnostic code in their EMR for psoriasis during the 12 months after the index psoriasis entry. The identified group averaged 50 years old; 55% of the psoriasis patients were women, and 86% were white.
During the year after their first diagnostic-code entry for psoriasis, 4.6% of the patients received a biological drug and 4.2% received an oral drug for their psoriasis. During 5.6 years of follow-up, 4,288 patients (2%) developed PsA, a rate of 3.5 cases/1,000 patient-years. Dr. Ogdie noted that prior studies have documented the challenge of diagnosing PsA in patients with psoriasis, so this may be a conservative estimate of the progression rate.
The researchers assessed possible linkage with PsA progression for more than 250 different entries in the EMR, but the analysis was limited by the absence of measures of rheumatoid susceptibility, such as immunologic markers, which were not included in the EMR. In multivariate analysis of the full cohort, fatigue at baseline was linked with a 77% higher rate of progression to PsA, obesity was linked with a 48% higher rate, and depression with a 29% higher rate of progression when compared with psoriasis patients without each of these factors. All three differences were statistically significant. Dr. Ogdie cited an article she recently coauthored that detailed the background to this approach in studying the etiology of PsA (Nat Rev Rheumatol. 2019 March;15:153-66).
This is the first study to report sex-linked differences in clinical measures that link with progression to PsA, Dr. Ogdie noted. In women, salmonella infection linked with a 9-fold higher rate of PsA development compared with women with psoriasis without salmonella infection, women with uveitis had a 2.9-fold higher rate of PsA development, and those with sepsis had a 2.4-fold increased rate of PsA. Among men, those with gangrene, encephalitis, or hidradenitis suppurativa each had a greater than 4-fold higher rate of developing PsA, and men with osteomyelitis had a 2.7-fold increase.
All these between-group differences were statistically significant. But because each of these was a relatively rare event, the confidence intervals around these point estimates were wide. For example, in women with salmonella infection from a statistical standpoint the possible range of increased risk could be anywhere from 1.3 to 66. The analysis identified among women and men several additional sex-specific risk associations that were statistically significant but with smaller point estimates.
SOURCE: Ogdie A et al. Ann Rheum Dis. Jun 2019;78(Suppl 2):131-2. Abstract OP0115. doi: 10.1136/annrheumdis-2019-eular.4390.
REPORTING FROM THE EULAR 2019 CONGRESS