Ankylosing spondylitis

Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.

“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”

The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
 

Activity limitations rose faster than predicted

According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.

The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.

“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”

Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).

The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”

The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).

Comments on latest findings

Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”

As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”

It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”

Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”

The authors and LaValley have disclosed no relevant financial relationships.

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

Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.

“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”

The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
 

Activity limitations rose faster than predicted

According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.

The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.

“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”

Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).

The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”

The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).

Comments on latest findings

Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”

As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”

It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”

Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”

The authors and LaValley have disclosed no relevant financial relationships.

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

Nearly a quarter of adults in the United States have been diagnosed with various forms of arthritis, new federal estimates report. The disorders limit the activities of 43.9% of them. Researchers also report that adults with poorer mental or physical health and those who are more disadvantaged socially are most vulnerable to arthritis.

“There is a substantial unmet need for existing, evidence-based, arthritis-appropriate interventions for people with arthritis to minimize activity limitations,” study coauthor and Centers for Disease Control and Prevention epidemiologist Kristina Theis, PhD, MPH, told this news organization. “Our findings show that interventions addressing self-management, education, physical activity, workplace accommodations, and mental health, among other areas, are all indicated for people with arthritis.”

The CDC report was published Oct. 8 in Morbidity and Mortality Weekly Report. Researchers estimated the number of arthritis cases on the basis of in-person interviews conducted with tens of thousands of U.S. adults as part of the National Health Interview Survey during 2016-2018. In the report, the researchers considered arthritis to include general arthritis, rheumatoid arthritis, gout, lupus, and fibromyalgia.
 

Activity limitations rose faster than predicted

According to the report, an estimated 58.5 million U.S. adults (23.7%; 21.5% age-standardized) told interviewers that they had been diagnosed with arthritis conditions. Of those, 25.7 million (43.9%; 40.8% age-standardized) had arthritis-attributable activity limitations (AAALs), which represents 10.4% of all adults.

The number of adults who reported having arthritis rose by 4.1 million from previous estimates for the years 2013-2015, a number that’s on pace with predictions. The number in the AAAL category rose by 2 million, a jump that’s higher than what had been predicted.

“The aging of the population is one factor in the increasing number of people with arthritis, even though arthritis is not an inevitable part of aging,” Dr. Theis said. “Individual factors, such as body mass index or other health conditions, and societal factors, such as educational and economic opportunities, likely play a role.”

Arthritis was especially common among those aged ≥ 65 years (50.4%), those who were unable to work or were disabled (52.3%), and those who self-reported fair/poor health (51.2%) or joint symptoms in the past 30 days (52.2%). The rate of arthritis was also high among those whose activities of daily living (ADL) were limited (54.8%) and those whose instrumental activities of daily living (IADL) were limited (55.9%).

The researchers report that the percentage of AAAL was also high among the following groups: “adults with joint symptoms in the past 30 days (51.6%), adults who were unable to work or disabled (54.7%), adults of other/multiple races (54.5%) or non-Hispanic American Indian or Alaska Natives (60.7%), adults with low income (53.3%) or poor/near poor income-to-poverty ratios (63.3%), or with moderate psychological distress (59.5%). AAAL was reported by a high proportion of adults with arthritis who had an ADL disability (82.6%), IADL disability (80.4%), serious psychological distress (76.3%), or fair/poor self-rated health (72.6%).”

The researchers found that among all adults with arthritis, the percentage of adults with arthritis was high among women (59.3%), those with obesity or overweight (74.2%), and those who weren’t sufficiently active (58%).

Comments on latest findings

Michael LaValley, PhD, biostatistician at the Boston University School of Public Health, who has studied arthritis statistics, told this news organization that the findings “fall right in line with the trends that have been observed in arthritis over the past 20 years. The prevalence is increasing, which certainly seems to be influenced by the aging population in the U.S.”

As for specific conditions, he said the rate of osteoarthritis may be influenced by older Americans and by those with obesity and sedentary behavior. “There is also some thinking that there may be environmental factors increasing the risk for some types of arthritis, but nothing conclusive. There also may be more clinical attention paid to arthritic conditions, leading to more people being diagnosed or even just suspecting that they have arthritis.”

It’s difficult to disentangle connections between arthritis and risk factors such as poverty, he said. “There almost certainly are occupational exposures that put people at risk of osteoarthritis – having to kneel, stoop, and lift heavy things – or other musculoskeletal conditions like lower back pain. These exposures are most likely in jobs that would predominantly go to people with few other options because of lower levels of income and education. People in these jobs would also be more likely to have financial stresses that lead to increased psychological distress and less time to take care of their health.”

Also, he said, “There is probably some reverse causation with the occupational results, self-related health, and psychological distress. These could all be affected by a person’s arthritis. Having arthritis may interfere with getting a better-paying job, and arthritis could certainly reduce someone’s self-reported health and induce psychological distress.”

The authors and LaValley have disclosed no relevant financial relationships.

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

The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.

The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.

Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.

The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.

Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.

[email protected]

The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.

The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.

Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.

The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.

Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.

[email protected]

The Food and Drug Administration approved a supplement to the biologics license application of the adalimumab biosimilar drug Cyltezo (adalimumab-adbm) that makes it the first interchangeable biosimilar with Humira (adalimumab), the original branded version of the drug, its manufacturer Boehringer Ingelheim announced Oct. 15.

The FDA originally approved Cyltezo in 2017 for the treatment of multiple chronic inflammatory diseases, including seven of Humira’s nine indications for adults and pediatric patients: rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and plaque psoriasis.

The interchangeability designation means that Cyltezo was tested in an additional clinical trial in which patients were successfully switched back and forth multiple times from Humira to Cyltezo and allows pharmacists to autosubstitute Humira with Cyltezo. In these cases, individual state laws control how and whether physicians will be notified of this switch.

Cyltezo is just the second biosimilar to be designated as interchangeable with its originator biologic product. The first approval, announced July 28, was for the interchangeability of Semglee (insulin glargine-yfgn) with the originator Lantus.

The agency based its decision on positive data from the VOLTAIRE-X study of 238 patients with moderate to severe chronic plaque psoriasis in which Cyltezo had no meaningful clinical differences from Humira in pharmacokinetics, efficacy, immunogenicity, and safety between the switching and continuous treatment groups.

Cyltezo will not be commercially available in the United States until July 1, 2023, according to Boehringer Ingelheim.

[email protected]

The selective and reversible Janus kinase inhibitor upadacitinib (Rinvoq) significantly improved symptoms in adults with either ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) when compared with placebo in a pair of studies from the phase 3 SELECT-AXIS 2 clinical trial, according to press releases issued Oct. 7 by manufacturer AbbVie.

Upadacitinib is currently approved in the European Union for patients with active AS, as well as patients with moderate to severe active rheumatoid arthritis and active psoriatic arthritis. Upadacitinib is approved by the Food and Drug Administration for adults with moderately to severely active RA, but is not currently approved for active AS or nr-axSpA.

In study 1, significantly more patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS 40) response criteria at week 14, compared with placebo (45% vs. 18%) after 14 weeks (P < .0001).

The study of 420 patients with an inadequate response to biologic disease-modifying antirheumatic drug therapy gave half upadacitinib for 104 weeks and the other half placebo for 14 weeks, followed by upadacitinib for 90 weeks.

Patients treated with upadacitinib showed significant improvements in secondary endpoints of back pain, inflammation, physical function, and disease activity at week 14, compared with placebo.

Significantly more upadacitinib- than placebo-treated patients reached low disease activity on the AS Disease Activity Score (ASDAS) (44% vs. 10%). Upadacitinib also led to significantly greater improvements from baseline than did placebo on MRI Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Spine, Patient’s Assessment of Total Back Pain, and Bath AS Functional Index (BASFI) score (–2.26 vs. –1.09).

COVID-19 and headache were the most common adverse events that were seen with upadacitinib during the first 14 weeks of the study (occurring in 3% or more). No adverse events led to study discontinuation among patients taking upadacitinib, compared with 1.4% on placebo, and serious adverse events were reported in 2.8% taking upadacitinib and in 0.5% on placebo. Serious infections with upadacitinib included four cases of COVID-19 and one case of uveitis.

Study 2 in patients with nr-axSpA

Study 2, which included 313 adults with nr-axSpA, yielded results similar to those of study 1 on the primary endpoint of meeting ASAS40 response criteria at week 14 (45% with upadacitinib 15 mg once daily vs. 23% with placebo; P < .0001), as well as on a variety of secondary efficacy endpoints and safety data.

Significantly better responses were observed at week 14 with upadacitinib for rate of low disease activity according to ASDAS (42% vs. 18%), changes in MRI SPARCC Scores for SI joints (–2.49 vs. 0.57), Patient’s Assessment of Total Back Pain (-2.91 vs. -2.00), and physical function based on the BASFI (–2.61 vs. –1.47).

The most common adverse events at 14 weeks, occurring in at least 3% of patients taking upadacitinib, included headache, COVID-19, nasopharyngitis, and nausea. Adverse events leading to study discontinuation occurred in 2.6% with upadacitinib and 1.3% with placebo; serious adverse events occurred in 2.6% and 1.3%, respectively.

Serious infections included COVID-19-induced pneumonia and pyelonephritis in patients taking upadacitinib and one case of hemorrhagic fever with renal syndrome with placebo.

The full results of the SELECT-AXIS 2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal, according to AbbVie.

The selective and reversible Janus kinase inhibitor upadacitinib (Rinvoq) significantly improved symptoms in adults with either ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) when compared with placebo in a pair of studies from the phase 3 SELECT-AXIS 2 clinical trial, according to press releases issued Oct. 7 by manufacturer AbbVie.

Upadacitinib is currently approved in the European Union for patients with active AS, as well as patients with moderate to severe active rheumatoid arthritis and active psoriatic arthritis. Upadacitinib is approved by the Food and Drug Administration for adults with moderately to severely active RA, but is not currently approved for active AS or nr-axSpA.

In study 1, significantly more patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS 40) response criteria at week 14, compared with placebo (45% vs. 18%) after 14 weeks (P < .0001).

The study of 420 patients with an inadequate response to biologic disease-modifying antirheumatic drug therapy gave half upadacitinib for 104 weeks and the other half placebo for 14 weeks, followed by upadacitinib for 90 weeks.

Patients treated with upadacitinib showed significant improvements in secondary endpoints of back pain, inflammation, physical function, and disease activity at week 14, compared with placebo.

Significantly more upadacitinib- than placebo-treated patients reached low disease activity on the AS Disease Activity Score (ASDAS) (44% vs. 10%). Upadacitinib also led to significantly greater improvements from baseline than did placebo on MRI Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Spine, Patient’s Assessment of Total Back Pain, and Bath AS Functional Index (BASFI) score (–2.26 vs. –1.09).

COVID-19 and headache were the most common adverse events that were seen with upadacitinib during the first 14 weeks of the study (occurring in 3% or more). No adverse events led to study discontinuation among patients taking upadacitinib, compared with 1.4% on placebo, and serious adverse events were reported in 2.8% taking upadacitinib and in 0.5% on placebo. Serious infections with upadacitinib included four cases of COVID-19 and one case of uveitis.

Study 2 in patients with nr-axSpA

Study 2, which included 313 adults with nr-axSpA, yielded results similar to those of study 1 on the primary endpoint of meeting ASAS40 response criteria at week 14 (45% with upadacitinib 15 mg once daily vs. 23% with placebo; P < .0001), as well as on a variety of secondary efficacy endpoints and safety data.

Significantly better responses were observed at week 14 with upadacitinib for rate of low disease activity according to ASDAS (42% vs. 18%), changes in MRI SPARCC Scores for SI joints (–2.49 vs. 0.57), Patient’s Assessment of Total Back Pain (-2.91 vs. -2.00), and physical function based on the BASFI (–2.61 vs. –1.47).

The most common adverse events at 14 weeks, occurring in at least 3% of patients taking upadacitinib, included headache, COVID-19, nasopharyngitis, and nausea. Adverse events leading to study discontinuation occurred in 2.6% with upadacitinib and 1.3% with placebo; serious adverse events occurred in 2.6% and 1.3%, respectively.

Serious infections included COVID-19-induced pneumonia and pyelonephritis in patients taking upadacitinib and one case of hemorrhagic fever with renal syndrome with placebo.

The full results of the SELECT-AXIS 2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal, according to AbbVie.

The selective and reversible Janus kinase inhibitor upadacitinib (Rinvoq) significantly improved symptoms in adults with either ankylosing spondylitis (AS) or nonradiographic axial spondyloarthritis (nr-axSpA) when compared with placebo in a pair of studies from the phase 3 SELECT-AXIS 2 clinical trial, according to press releases issued Oct. 7 by manufacturer AbbVie.

Upadacitinib is currently approved in the European Union for patients with active AS, as well as patients with moderate to severe active rheumatoid arthritis and active psoriatic arthritis. Upadacitinib is approved by the Food and Drug Administration for adults with moderately to severely active RA, but is not currently approved for active AS or nr-axSpA.

In study 1, significantly more patients with AS who were randomly assigned to upadacitinib 15 mg once daily met the primary endpoint of 40% improvement in Assessment in Spondyloarthritis International Society (ASAS 40) response criteria at week 14, compared with placebo (45% vs. 18%) after 14 weeks (P < .0001).

The study of 420 patients with an inadequate response to biologic disease-modifying antirheumatic drug therapy gave half upadacitinib for 104 weeks and the other half placebo for 14 weeks, followed by upadacitinib for 90 weeks.

Patients treated with upadacitinib showed significant improvements in secondary endpoints of back pain, inflammation, physical function, and disease activity at week 14, compared with placebo.

Significantly more upadacitinib- than placebo-treated patients reached low disease activity on the AS Disease Activity Score (ASDAS) (44% vs. 10%). Upadacitinib also led to significantly greater improvements from baseline than did placebo on MRI Spondyloarthritis Research Consortium of Canada (SPARCC) Score for Spine, Patient’s Assessment of Total Back Pain, and Bath AS Functional Index (BASFI) score (–2.26 vs. –1.09).

COVID-19 and headache were the most common adverse events that were seen with upadacitinib during the first 14 weeks of the study (occurring in 3% or more). No adverse events led to study discontinuation among patients taking upadacitinib, compared with 1.4% on placebo, and serious adverse events were reported in 2.8% taking upadacitinib and in 0.5% on placebo. Serious infections with upadacitinib included four cases of COVID-19 and one case of uveitis.

Study 2 in patients with nr-axSpA

Study 2, which included 313 adults with nr-axSpA, yielded results similar to those of study 1 on the primary endpoint of meeting ASAS40 response criteria at week 14 (45% with upadacitinib 15 mg once daily vs. 23% with placebo; P < .0001), as well as on a variety of secondary efficacy endpoints and safety data.

Significantly better responses were observed at week 14 with upadacitinib for rate of low disease activity according to ASDAS (42% vs. 18%), changes in MRI SPARCC Scores for SI joints (–2.49 vs. 0.57), Patient’s Assessment of Total Back Pain (-2.91 vs. -2.00), and physical function based on the BASFI (–2.61 vs. –1.47).

The most common adverse events at 14 weeks, occurring in at least 3% of patients taking upadacitinib, included headache, COVID-19, nasopharyngitis, and nausea. Adverse events leading to study discontinuation occurred in 2.6% with upadacitinib and 1.3% with placebo; serious adverse events occurred in 2.6% and 1.3%, respectively.

Serious infections included COVID-19-induced pneumonia and pyelonephritis in patients taking upadacitinib and one case of hemorrhagic fever with renal syndrome with placebo.

The full results of the SELECT-AXIS 2 trial will be presented at a future medical meeting and submitted for publication in a peer-reviewed journal, according to AbbVie.

It took years for Elle Moxley to get a diagnosis that explained her crippling gastrointestinal pain, digestion problems, fatigue, and hot, red rashes. And after learning in 2016 that she had Crohn’s disease, a chronic inflammation of the digestive tract, she spent more than 4 years trying medications before getting her disease under control with a biologic drug called Remicade.

So Ms. Moxley, 33, was dismayed to receive a notice from her insurer in January that Remicade would no longer be covered as a preferred drug on her plan. Another drug, Inflectra, which the Food and Drug Administration says has no meaningful clinical differences from Remicade, is now preferred. It is a “biosimilar” drug.

“I felt very powerless,” said Ms. Moxley, who recently started a job as a public relations coordinator for Kansas City (Mo.) Public Schools. “I have this decision being made for me and my doctor that’s not in my best interest, and it might knock me out of remission.”

After Ms. Moxley’s first Inflectra infusion in July, she developed a painful rash. It went away after a few days, but she said she continues to feel extremely fatigued and experiences gastrointestinal pain, constipation, diarrhea and nausea.

Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe to cut costs.

Yet the United States has been slower to adopt biosimilar drugs since the first such medicine was approved in 2015. That’s partly because of concerns raised by patients like Moxley and their doctors, but also because brand-name biologics have kept biosimilars from entering the market. The companies behind the brand-name drugs have used legal actions to extend the life of their patents and incentives that make offering the brand biologic more attractive than offering a biosimilar on a formulary, listing which drugs are covered on an insurance plan.

“It distorts the market and makes it so that patients can’t get access,” said Jinoos Yazdany, MD, MPH, a professor of medicine and chief of the rheumatology division at Zuckerberg San Francisco General Hospital.

The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market, according to an analysis by NORC, a research organization at the University of Chicago.

Remicade’s manufacturer, Johnson & Johnson, and Pfizer, which makes the Remicade biosimilar Inflectra, have been embroiled in a long-running lawsuit over Pfizer’s claims that Johnson & Johnson tried to choke off competition through exclusionary contracts with insurers and other anticompetitive actions. In July, the companies settled the case on undisclosed terms.

In a statement, Pfizer said it would continue to sell Inflectra in the United States but noted ongoing challenges: “Pfizer has begun to see progress in the overall biosimilars marketplace in the U.S. However, changes in policy at a government level and acceptance of biosimilars among key stakeholders are critical to deliver more meaningful uptake so patients and the health care system at large can benefit from the cost savings these medicines may deliver.”

Johnson & Johnson said it is committed to making Remicade available to patients who choose it, which “compels us to compete responsibly on both price and value.”

Biologic medicines, which are generally grown from living organisms such as animal cells or bacteria, are more complex and expensive to manufacture than drugs made from chemicals. In recent years, biologic drugs have become a mainstay of treatment for autoimmune conditions like Crohn’s disease and rheumatoid arthritis, as well as certain cancers and diabetes, among other conditions.

Other drugmakers can’t exactly reproduce these biologic drugs by following chemical recipes as they do for generic versions of conventional drugs.

Instead, biosimilar versions of biologic drugs are generally made from the same types of materials as the original biologics and must be “highly similar” to them to be approved by the FDA. They must have no clinically meaningful differences from the biologic drug, and be just as safe, pure and potent. More than a decade after Congress created an approval pathway for biosimilars, they are widely accepted as safe and effective alternatives to brand biologics.

Medical experts hope that as biosimilars become more widely used they will increasingly provide a brake on drug spending.

From 2015 to 2019, drug spending overall grew 6.1%, while spending on biologics grew more than twice as much – 14.6% – according to a report by IQVIA, a health care analytics company. In 2019, biologics accounted for 43% of drug spending in the United States

Biosimilars provide a roughly 30% discount over brand biologics in the United States but have the potential to reduce spending by more than $100 billion in the next 5 years, the IQVIA analysis found.

In a survey of 602 physicians who prescribe biologic medications, more than three-quarters said they believed biosimilars are just as safe and effective as their biologic counterparts, according to NORC.

But they were less comfortable with switching patients from a brand biologic to a biosimilar. While about half said they were very likely to prescribe a biosimilar to a patient just starting biologic therapy, only 31% said they were very likely to prescribe a biosimilar to a patient already doing well on a brand biologic.

It can be challenging to find a treatment regimen that works for patients with complicated chronic conditions, and physicians and patients often don’t want to rock the boat once that is achieved.

In Ms. Moxley’s case, for example, before her condition stabilized on Remicade, she tried a conventional pill called Lialda, the biologic drug Humira and a lower dose of Remicade.

Some doctors and patients raise concerns that switching between these drugs might cause patients to develop antibodies that cause the drugs to lose effectiveness. They want to see more research about the effects of such switches.

“We haven’t seen enough studies about patients going from the biologic to the biosimilar and bouncing back and forth,” said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We don’t want our patients to be guinea pigs.”

Manufacturers of biologic and biosimilar drugs have participated in advertising, exhibit or sponsorship opportunities with the American College of Rheumatology, according to ACR spokesperson Jocelyn Givens.

But studies show a one-time switch from Remicade to a biosimilar like Inflectra does not cause side effects or the development of antibodies, said Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, and former member of the Crohn’s & Colitis Foundation’s National Scientific Advisory Committee. Studies may be conducted by researchers with extensive ties to the industry and funded by drugmakers.

Situations like Ms. Moxley’s are unusual, said Kristine Grow, senior vice president of communications at AHIP, an insurer trade group.

“For patients who have been taking a brand-name biologic for some time, health insurance providers do not typically encourage them to switch to a biosimilar because of a formulary change, and most plans exclude these patients from any changes in cost sharing due to formulary changes,” she said.

Drugmakers can seek approval from the FDA of their biosimilar as interchangeable with a biologic drug, allowing pharmacists, subject to state law, to switch a physician’s prescription from the brand drug, as they often do with generic drugs.

However, the FDA has approved only one biosimilar (Semglee, a form of insulin) as interchangeable with a biologic (Lantus).

Like Ms. Moxley, many other patients using biologics get copay assistance from drug companies, but the money often isn’t enough to cover the full cost. In her old job as a radio reporter, Ms. Moxley said, she hit the $7,000 maximum annual out-of-pocket spending limit for her plan by May.

In her new job, Ms. Moxley has an individual plan with a $4,000 maximum out-of-pocket limit, which she expects to blow past once again within months.

But she received good news recently: Her new plan will cover Remicade.

“I’m still concerned that I will have developed antibodies since my last dose,” she said. “But it feels like a step in the direction of good health again.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

It took years for Elle Moxley to get a diagnosis that explained her crippling gastrointestinal pain, digestion problems, fatigue, and hot, red rashes. And after learning in 2016 that she had Crohn’s disease, a chronic inflammation of the digestive tract, she spent more than 4 years trying medications before getting her disease under control with a biologic drug called Remicade.

So Ms. Moxley, 33, was dismayed to receive a notice from her insurer in January that Remicade would no longer be covered as a preferred drug on her plan. Another drug, Inflectra, which the Food and Drug Administration says has no meaningful clinical differences from Remicade, is now preferred. It is a “biosimilar” drug.

“I felt very powerless,” said Ms. Moxley, who recently started a job as a public relations coordinator for Kansas City (Mo.) Public Schools. “I have this decision being made for me and my doctor that’s not in my best interest, and it might knock me out of remission.”

After Ms. Moxley’s first Inflectra infusion in July, she developed a painful rash. It went away after a few days, but she said she continues to feel extremely fatigued and experiences gastrointestinal pain, constipation, diarrhea and nausea.

Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe to cut costs.

Yet the United States has been slower to adopt biosimilar drugs since the first such medicine was approved in 2015. That’s partly because of concerns raised by patients like Moxley and their doctors, but also because brand-name biologics have kept biosimilars from entering the market. The companies behind the brand-name drugs have used legal actions to extend the life of their patents and incentives that make offering the brand biologic more attractive than offering a biosimilar on a formulary, listing which drugs are covered on an insurance plan.

“It distorts the market and makes it so that patients can’t get access,” said Jinoos Yazdany, MD, MPH, a professor of medicine and chief of the rheumatology division at Zuckerberg San Francisco General Hospital.

The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market, according to an analysis by NORC, a research organization at the University of Chicago.

Remicade’s manufacturer, Johnson & Johnson, and Pfizer, which makes the Remicade biosimilar Inflectra, have been embroiled in a long-running lawsuit over Pfizer’s claims that Johnson & Johnson tried to choke off competition through exclusionary contracts with insurers and other anticompetitive actions. In July, the companies settled the case on undisclosed terms.

In a statement, Pfizer said it would continue to sell Inflectra in the United States but noted ongoing challenges: “Pfizer has begun to see progress in the overall biosimilars marketplace in the U.S. However, changes in policy at a government level and acceptance of biosimilars among key stakeholders are critical to deliver more meaningful uptake so patients and the health care system at large can benefit from the cost savings these medicines may deliver.”

Johnson & Johnson said it is committed to making Remicade available to patients who choose it, which “compels us to compete responsibly on both price and value.”

Biologic medicines, which are generally grown from living organisms such as animal cells or bacteria, are more complex and expensive to manufacture than drugs made from chemicals. In recent years, biologic drugs have become a mainstay of treatment for autoimmune conditions like Crohn’s disease and rheumatoid arthritis, as well as certain cancers and diabetes, among other conditions.

Other drugmakers can’t exactly reproduce these biologic drugs by following chemical recipes as they do for generic versions of conventional drugs.

Instead, biosimilar versions of biologic drugs are generally made from the same types of materials as the original biologics and must be “highly similar” to them to be approved by the FDA. They must have no clinically meaningful differences from the biologic drug, and be just as safe, pure and potent. More than a decade after Congress created an approval pathway for biosimilars, they are widely accepted as safe and effective alternatives to brand biologics.

Medical experts hope that as biosimilars become more widely used they will increasingly provide a brake on drug spending.

From 2015 to 2019, drug spending overall grew 6.1%, while spending on biologics grew more than twice as much – 14.6% – according to a report by IQVIA, a health care analytics company. In 2019, biologics accounted for 43% of drug spending in the United States

Biosimilars provide a roughly 30% discount over brand biologics in the United States but have the potential to reduce spending by more than $100 billion in the next 5 years, the IQVIA analysis found.

In a survey of 602 physicians who prescribe biologic medications, more than three-quarters said they believed biosimilars are just as safe and effective as their biologic counterparts, according to NORC.

But they were less comfortable with switching patients from a brand biologic to a biosimilar. While about half said they were very likely to prescribe a biosimilar to a patient just starting biologic therapy, only 31% said they were very likely to prescribe a biosimilar to a patient already doing well on a brand biologic.

It can be challenging to find a treatment regimen that works for patients with complicated chronic conditions, and physicians and patients often don’t want to rock the boat once that is achieved.

In Ms. Moxley’s case, for example, before her condition stabilized on Remicade, she tried a conventional pill called Lialda, the biologic drug Humira and a lower dose of Remicade.

Some doctors and patients raise concerns that switching between these drugs might cause patients to develop antibodies that cause the drugs to lose effectiveness. They want to see more research about the effects of such switches.

“We haven’t seen enough studies about patients going from the biologic to the biosimilar and bouncing back and forth,” said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We don’t want our patients to be guinea pigs.”

Manufacturers of biologic and biosimilar drugs have participated in advertising, exhibit or sponsorship opportunities with the American College of Rheumatology, according to ACR spokesperson Jocelyn Givens.

But studies show a one-time switch from Remicade to a biosimilar like Inflectra does not cause side effects or the development of antibodies, said Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, and former member of the Crohn’s & Colitis Foundation’s National Scientific Advisory Committee. Studies may be conducted by researchers with extensive ties to the industry and funded by drugmakers.

Situations like Ms. Moxley’s are unusual, said Kristine Grow, senior vice president of communications at AHIP, an insurer trade group.

“For patients who have been taking a brand-name biologic for some time, health insurance providers do not typically encourage them to switch to a biosimilar because of a formulary change, and most plans exclude these patients from any changes in cost sharing due to formulary changes,” she said.

Drugmakers can seek approval from the FDA of their biosimilar as interchangeable with a biologic drug, allowing pharmacists, subject to state law, to switch a physician’s prescription from the brand drug, as they often do with generic drugs.

However, the FDA has approved only one biosimilar (Semglee, a form of insulin) as interchangeable with a biologic (Lantus).

Like Ms. Moxley, many other patients using biologics get copay assistance from drug companies, but the money often isn’t enough to cover the full cost. In her old job as a radio reporter, Ms. Moxley said, she hit the $7,000 maximum annual out-of-pocket spending limit for her plan by May.

In her new job, Ms. Moxley has an individual plan with a $4,000 maximum out-of-pocket limit, which she expects to blow past once again within months.

But she received good news recently: Her new plan will cover Remicade.

“I’m still concerned that I will have developed antibodies since my last dose,” she said. “But it feels like a step in the direction of good health again.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

It took years for Elle Moxley to get a diagnosis that explained her crippling gastrointestinal pain, digestion problems, fatigue, and hot, red rashes. And after learning in 2016 that she had Crohn’s disease, a chronic inflammation of the digestive tract, she spent more than 4 years trying medications before getting her disease under control with a biologic drug called Remicade.

So Ms. Moxley, 33, was dismayed to receive a notice from her insurer in January that Remicade would no longer be covered as a preferred drug on her plan. Another drug, Inflectra, which the Food and Drug Administration says has no meaningful clinical differences from Remicade, is now preferred. It is a “biosimilar” drug.

“I felt very powerless,” said Ms. Moxley, who recently started a job as a public relations coordinator for Kansas City (Mo.) Public Schools. “I have this decision being made for me and my doctor that’s not in my best interest, and it might knock me out of remission.”

After Ms. Moxley’s first Inflectra infusion in July, she developed a painful rash. It went away after a few days, but she said she continues to feel extremely fatigued and experiences gastrointestinal pain, constipation, diarrhea and nausea.

Many medical professionals look to biosimilar drugs as a way to increase competition and give consumers cheaper options, much as generic drugs do, and they point to the more robust use of these products in Europe to cut costs.

Yet the United States has been slower to adopt biosimilar drugs since the first such medicine was approved in 2015. That’s partly because of concerns raised by patients like Moxley and their doctors, but also because brand-name biologics have kept biosimilars from entering the market. The companies behind the brand-name drugs have used legal actions to extend the life of their patents and incentives that make offering the brand biologic more attractive than offering a biosimilar on a formulary, listing which drugs are covered on an insurance plan.

“It distorts the market and makes it so that patients can’t get access,” said Jinoos Yazdany, MD, MPH, a professor of medicine and chief of the rheumatology division at Zuckerberg San Francisco General Hospital.

The FDA has approved 31 biosimilar medications since 2015, but only about 60% have made it to market, according to an analysis by NORC, a research organization at the University of Chicago.

Remicade’s manufacturer, Johnson & Johnson, and Pfizer, which makes the Remicade biosimilar Inflectra, have been embroiled in a long-running lawsuit over Pfizer’s claims that Johnson & Johnson tried to choke off competition through exclusionary contracts with insurers and other anticompetitive actions. In July, the companies settled the case on undisclosed terms.

In a statement, Pfizer said it would continue to sell Inflectra in the United States but noted ongoing challenges: “Pfizer has begun to see progress in the overall biosimilars marketplace in the U.S. However, changes in policy at a government level and acceptance of biosimilars among key stakeholders are critical to deliver more meaningful uptake so patients and the health care system at large can benefit from the cost savings these medicines may deliver.”

Johnson & Johnson said it is committed to making Remicade available to patients who choose it, which “compels us to compete responsibly on both price and value.”

Biologic medicines, which are generally grown from living organisms such as animal cells or bacteria, are more complex and expensive to manufacture than drugs made from chemicals. In recent years, biologic drugs have become a mainstay of treatment for autoimmune conditions like Crohn’s disease and rheumatoid arthritis, as well as certain cancers and diabetes, among other conditions.

Other drugmakers can’t exactly reproduce these biologic drugs by following chemical recipes as they do for generic versions of conventional drugs.

Instead, biosimilar versions of biologic drugs are generally made from the same types of materials as the original biologics and must be “highly similar” to them to be approved by the FDA. They must have no clinically meaningful differences from the biologic drug, and be just as safe, pure and potent. More than a decade after Congress created an approval pathway for biosimilars, they are widely accepted as safe and effective alternatives to brand biologics.

Medical experts hope that as biosimilars become more widely used they will increasingly provide a brake on drug spending.

From 2015 to 2019, drug spending overall grew 6.1%, while spending on biologics grew more than twice as much – 14.6% – according to a report by IQVIA, a health care analytics company. In 2019, biologics accounted for 43% of drug spending in the United States

Biosimilars provide a roughly 30% discount over brand biologics in the United States but have the potential to reduce spending by more than $100 billion in the next 5 years, the IQVIA analysis found.

In a survey of 602 physicians who prescribe biologic medications, more than three-quarters said they believed biosimilars are just as safe and effective as their biologic counterparts, according to NORC.

But they were less comfortable with switching patients from a brand biologic to a biosimilar. While about half said they were very likely to prescribe a biosimilar to a patient just starting biologic therapy, only 31% said they were very likely to prescribe a biosimilar to a patient already doing well on a brand biologic.

It can be challenging to find a treatment regimen that works for patients with complicated chronic conditions, and physicians and patients often don’t want to rock the boat once that is achieved.

In Ms. Moxley’s case, for example, before her condition stabilized on Remicade, she tried a conventional pill called Lialda, the biologic drug Humira and a lower dose of Remicade.

Some doctors and patients raise concerns that switching between these drugs might cause patients to develop antibodies that cause the drugs to lose effectiveness. They want to see more research about the effects of such switches.

“We haven’t seen enough studies about patients going from the biologic to the biosimilar and bouncing back and forth,” said Marcus Snow, MD, chair of the American College of Rheumatology’s Committee on Rheumatologic Care. “We don’t want our patients to be guinea pigs.”

Manufacturers of biologic and biosimilar drugs have participated in advertising, exhibit or sponsorship opportunities with the American College of Rheumatology, according to ACR spokesperson Jocelyn Givens.

But studies show a one-time switch from Remicade to a biosimilar like Inflectra does not cause side effects or the development of antibodies, said Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s Hospital in Columbus, Ohio, and former member of the Crohn’s & Colitis Foundation’s National Scientific Advisory Committee. Studies may be conducted by researchers with extensive ties to the industry and funded by drugmakers.

Situations like Ms. Moxley’s are unusual, said Kristine Grow, senior vice president of communications at AHIP, an insurer trade group.

“For patients who have been taking a brand-name biologic for some time, health insurance providers do not typically encourage them to switch to a biosimilar because of a formulary change, and most plans exclude these patients from any changes in cost sharing due to formulary changes,” she said.

Drugmakers can seek approval from the FDA of their biosimilar as interchangeable with a biologic drug, allowing pharmacists, subject to state law, to switch a physician’s prescription from the brand drug, as they often do with generic drugs.

However, the FDA has approved only one biosimilar (Semglee, a form of insulin) as interchangeable with a biologic (Lantus).

Like Ms. Moxley, many other patients using biologics get copay assistance from drug companies, but the money often isn’t enough to cover the full cost. In her old job as a radio reporter, Ms. Moxley said, she hit the $7,000 maximum annual out-of-pocket spending limit for her plan by May.

In her new job, Ms. Moxley has an individual plan with a $4,000 maximum out-of-pocket limit, which she expects to blow past once again within months.

But she received good news recently: Her new plan will cover Remicade.

“I’m still concerned that I will have developed antibodies since my last dose,” she said. “But it feels like a step in the direction of good health again.”

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

“Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment,” John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

“We’re currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts,” Dr. Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Dr. Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a “little bit puzzling,” one delegate said after Dr. Reveille’s presentation. “The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy,” the delegate observed.

“I was confounded when I saw the data,” Dr. Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. “Interestingly, we have seen this negative association with some other parameters, too,” he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Dr. Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Dr. Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

“Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment,” John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

“We’re currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts,” Dr. Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Dr. Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a “little bit puzzling,” one delegate said after Dr. Reveille’s presentation. “The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy,” the delegate observed.

“I was confounded when I saw the data,” Dr. Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. “Interestingly, we have seen this negative association with some other parameters, too,” he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Dr. Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Dr. Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

Older age, higher subjective disease activity, and exercising for more than 120 minutes per week were three factors linked to patients with ankylosing spondylitis (AS) who switched from their original tumor necrosis factor inhibitor (TNFi) treatment within 2 years in a U.S.-based study.

Data from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS) also found that higher levels of inflammation, but not radiographic disease, were linked to patients changing from one TNFi to another, or to an interleukin (IL)-17 inhibitor or Janus kinase (JAK) inhibitor.

“Different factors were associated in AS patients who switch from their initial TNF inhibitor to another TNF inhibitor, IL-17 inhibitor, or JAK inhibitor within 2 years versus after 2 years of treatment,” John D. Reveille, MD, professor and vice chair of rheumatology and clinical immunogenetics with McGovern Medical School at UTHealth Houston, said at the 12th International Congress on Spondyloarthritides.

“We’re currently looking at different approaches to analyzing these data. And, certainly, this needs need to be looked at in other cohorts,” Dr. Reveille said.

PSOAS is a prospective observational cohort study that has been looking at predictors of AS severity for almost 20 years. Started in 2002, the study has routinely collected a whole host of data on various demographic and disease-related factors.

The reasoning behind the current analysis of PSOAS data was that a relatively recent study based on a commercial claims database had found that many patients with AS do not remain on their initial TNFi 2 years after initiation. So, Dr. Reveille and associates decided to look at the factors that could be influencing whether patients who started a TNFi would remain on their original drug in the PSOAS cohort.

In all, 533 patients from the PSOAS cohort who had at least 2 years of follow-up were included in the analysis. The majority (n = 496) were treated with a TNFi, 34 had received an IL-17 inhibitor, and 3 had received a JAK inhibitor.

Of the 496 patients treated with a TNFi, almost 70% (n = 344) persisted with this treatment for the duration of the study. Of those that switched to another TNFi or IL-17 or JAK inhibitor treatment, 20% (n = 101) did so within 2 years and the remaining 10% (n = 51) after 2 years.

Multinominal logistic regression modeling revealed a number of different factors that were associated with switching within 2 years versus switching after 2 years.

Compared to patients who persisted with treatment throughout the study period, patients who switched from their original TNFi within 2 years were more likely to be older (odds ratio [OR], 2.0 for ≥ 40 vs. < 40 years; P = .002), have a higher Bath Ankylosing Spondyloarthritis Disease Activity Index (BASDAI) score at baseline (OR, 1.73 for ≥ 4 vs. < 4; P = .03), higher C-reactive protein levels (OR, 1.94 for ≥ 0.8 mg/dL vs. < 0.8 mg/dL, P = .004), and greater weekly duration of exercise (OR, 1.95 for ≥ 120 minutes per week vs. < 120; P <.001).

Switchers also were less likely to have severe radiographic disease at baseline, as determined by the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS, OR, 0.63; P = .03), and less likely to be current smokers (OR, 0.69; P < .001).

Factors associated with switching after 2 years versus persisting with treatment were higher baseline BASDAI (OR, 2.31; P = .01), exercising more than 120 minutes per week (OR, 1.66; P = .03), and having more comorbidities (OR, 1.63 for ≥ 2 vs. < 2, P = .04).

However, patients who switched after 2 years were less likely to be depressed (OR, 0.35; P = .002) or to have a longer baseline disease duration (OR, 0.27 for ≥ 20 years vs. < 20 years P < .001).

The association observed between switching within 2 years and lower likelihood of currently smoking was a “little bit puzzling,” one delegate said after Dr. Reveille’s presentation. “The opposite has been shown in the literature, and current smokers seem to be refractory to TNF inhibitor therapy,” the delegate observed.

“I was confounded when I saw the data,” Dr. Reveille acknowledged. Because this was an observational study, this finding needs more investigation, he agreed. “Interestingly, we have seen this negative association with some other parameters, too,” he added.

The HLA-B27 carrier and radiographic status were carefully checked, so there should not be a problem with the diagnosis, Dr. Reveille reassured. Further analyses of the findings are now warranted.

Funding for the study was provided by the U.S. Department of Health and Human Services, the National Institutes of Health, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Additional funding was received from the Spondyloarthritis Association of America and Eli Lilly.

Dr. Reveille made no personal disclosures; a coauthor of the abstract was an employee of Eli Lilly.

How best to define axial spondyloarthritis (axSpA) flares in practice remains the subject of some debate as evidenced by the discussion that followed an abstract presentation at the 12th International Congress on Spondyloarthritides.

It’s an important topic, said Maxime Breban, MD, PhD, of Ambroise Paré Hospital in Paris, as flares can adversely affect patient outcomes. The absence of flares may also a useful measure of how well a patient is responding to treatment in clinical trials and whether a treatment can be tapered.

“There have been many ways to define flares in the past and there is no consensus,” he observed.

Although the Assessment of Spondyloarthritis International Society (ASAS) devised 12 preliminary definitions of flare in 2016, “these were not that good when we moved to patients,” Dr. Breban suggested.

The ASAS definitions were based on patient vignettes, he explained, and used a combination of variables from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a visual analog scale (VAS) of pain, and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP).

The study that Dr. Breban presented looked at the performance of the ASAS preliminary definitions of axSpA flares in a real-life patient population, as well as prospectively determining how variations in BASDAI and VAS pain were associated with patient-perceived flares of disease.

A total of 99 patients took part in the study, recruited through a secure e-health platform called SPONDY+. Once a week, patients completed the BASDAI questionnaire and the pain VAS, and stated whether their disease had flared in the past week.

Receiver operating characteristic (ROC) curves were calculated to see how well the BASDAI and pain VAS identified patients who were experiencing a flare or had a recently resolved flare of axSpA.

Dr. Breban reported that variation in the BASDAI “appears a suitable variable to monitor the occurrence and resolution of patient-reported flare in axial spondylarthritis.”

In predicting a flare, the area under the curve (AUC) was significantly higher for the change in BASDAI than for the change in pain VAS, at a respective 0.81 and 0.77 (P = .01). However, both variables were similarly accurate in predicting the resolution of a flare, with respective AUCs of 0.78 and 0.80 (P = .3).

A 0.22-point increase in BASDAI was reported to be the best balance between sensitivity (70%) and specificity (79%) for a flare. However, this is “outside of what is possible within a test–retest situation,” Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, said during discussion.

Dr. van der Heijde told Dr. Breban: “I understand that that comes out of your data, that that’s the best combination for sensitivity and specificity, but the next step is to decide if that makes sense.”

The ROC curves that Dr. Breban presented showed the range of sensitivities and specificities that could be achieved. If the specificity was increased to be 90% or higher, the specificity fell to 55%, with the change in BASDAI being an increase of 0.8 points. Conversely, bringing the sensitivity above 90% meant the specificity dropped to 39% and the change in BASDAI was a decrease of 0.1 point.

“So that means you can choose whatever you want as a cutoff,” Dr. Breban said. It depends on what you are aiming to do. “If you want to identify a flare, you can increase sensitivity, or specificity, according to what your purpose is,” he suggested.

“The next step, of course, is what to choose as a flare. Then it depends on how you want to use a flare if you want to use a flare to change the treatment,” agreed Dr. van der Heijde. “That was why, in the ASAS group, it was decided to have a high specificity so that you are not changing treatment all the time.”

In the data that Dr. Breban presented, the ASAS preliminary definitions were highly specific but lacked sensitivity. None of the ASAS definitions yielded sensitivity values higher than 37%, whereas specificity was higher than 95% for all of them.

The study’s design did not allow researchers to test the ASDAS-CRP as a definition of flare in its real-world patient sample. Thus, it is looking only at the patient’s perspective on flare, and there is a “huge discrepancy” between patient and physician-reported disease activity, Dr. van der Heijde noted. “So, I think before using your data to really choose the flare definition, I think we need to take it all into account.”

Maxime Dougados, MD, PhD, of Cochin Hospital in Paris, who has been “deeply involved in the elaboration of the definition of flare” added his thoughts: “Flare means for me, not a status, but a change,” he observed.

But if the aim of treating people with axSpA is to achieve a good or acceptable state of health, he questioned whether work should be continued to define the concept of a flare.

The definition of a flare was conceived for use in clinical trials mainly, Dr. van der Heijde noted. It helped to assess how changes in treatment might affect the outcomes of patients. In clinical practice, especially now with treat-to-target gaining more and more traction in axSpA, she agreed that perhaps the goal should be to focus more on the health status of patients.

Dr. Breban acknowledged that the SPONDY+ platform has been developed by bepatient with support from Merck Sharp & Dohme. No other disclosures were made.

How best to define axial spondyloarthritis (axSpA) flares in practice remains the subject of some debate as evidenced by the discussion that followed an abstract presentation at the 12th International Congress on Spondyloarthritides.

It’s an important topic, said Maxime Breban, MD, PhD, of Ambroise Paré Hospital in Paris, as flares can adversely affect patient outcomes. The absence of flares may also a useful measure of how well a patient is responding to treatment in clinical trials and whether a treatment can be tapered.

“There have been many ways to define flares in the past and there is no consensus,” he observed.

Although the Assessment of Spondyloarthritis International Society (ASAS) devised 12 preliminary definitions of flare in 2016, “these were not that good when we moved to patients,” Dr. Breban suggested.

The ASAS definitions were based on patient vignettes, he explained, and used a combination of variables from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a visual analog scale (VAS) of pain, and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP).

The study that Dr. Breban presented looked at the performance of the ASAS preliminary definitions of axSpA flares in a real-life patient population, as well as prospectively determining how variations in BASDAI and VAS pain were associated with patient-perceived flares of disease.

A total of 99 patients took part in the study, recruited through a secure e-health platform called SPONDY+. Once a week, patients completed the BASDAI questionnaire and the pain VAS, and stated whether their disease had flared in the past week.

Receiver operating characteristic (ROC) curves were calculated to see how well the BASDAI and pain VAS identified patients who were experiencing a flare or had a recently resolved flare of axSpA.

Dr. Breban reported that variation in the BASDAI “appears a suitable variable to monitor the occurrence and resolution of patient-reported flare in axial spondylarthritis.”

In predicting a flare, the area under the curve (AUC) was significantly higher for the change in BASDAI than for the change in pain VAS, at a respective 0.81 and 0.77 (P = .01). However, both variables were similarly accurate in predicting the resolution of a flare, with respective AUCs of 0.78 and 0.80 (P = .3).

A 0.22-point increase in BASDAI was reported to be the best balance between sensitivity (70%) and specificity (79%) for a flare. However, this is “outside of what is possible within a test–retest situation,” Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, said during discussion.

Dr. van der Heijde told Dr. Breban: “I understand that that comes out of your data, that that’s the best combination for sensitivity and specificity, but the next step is to decide if that makes sense.”

The ROC curves that Dr. Breban presented showed the range of sensitivities and specificities that could be achieved. If the specificity was increased to be 90% or higher, the specificity fell to 55%, with the change in BASDAI being an increase of 0.8 points. Conversely, bringing the sensitivity above 90% meant the specificity dropped to 39% and the change in BASDAI was a decrease of 0.1 point.

“So that means you can choose whatever you want as a cutoff,” Dr. Breban said. It depends on what you are aiming to do. “If you want to identify a flare, you can increase sensitivity, or specificity, according to what your purpose is,” he suggested.

“The next step, of course, is what to choose as a flare. Then it depends on how you want to use a flare if you want to use a flare to change the treatment,” agreed Dr. van der Heijde. “That was why, in the ASAS group, it was decided to have a high specificity so that you are not changing treatment all the time.”

In the data that Dr. Breban presented, the ASAS preliminary definitions were highly specific but lacked sensitivity. None of the ASAS definitions yielded sensitivity values higher than 37%, whereas specificity was higher than 95% for all of them.

The study’s design did not allow researchers to test the ASDAS-CRP as a definition of flare in its real-world patient sample. Thus, it is looking only at the patient’s perspective on flare, and there is a “huge discrepancy” between patient and physician-reported disease activity, Dr. van der Heijde noted. “So, I think before using your data to really choose the flare definition, I think we need to take it all into account.”

Maxime Dougados, MD, PhD, of Cochin Hospital in Paris, who has been “deeply involved in the elaboration of the definition of flare” added his thoughts: “Flare means for me, not a status, but a change,” he observed.

But if the aim of treating people with axSpA is to achieve a good or acceptable state of health, he questioned whether work should be continued to define the concept of a flare.

The definition of a flare was conceived for use in clinical trials mainly, Dr. van der Heijde noted. It helped to assess how changes in treatment might affect the outcomes of patients. In clinical practice, especially now with treat-to-target gaining more and more traction in axSpA, she agreed that perhaps the goal should be to focus more on the health status of patients.

Dr. Breban acknowledged that the SPONDY+ platform has been developed by bepatient with support from Merck Sharp & Dohme. No other disclosures were made.

How best to define axial spondyloarthritis (axSpA) flares in practice remains the subject of some debate as evidenced by the discussion that followed an abstract presentation at the 12th International Congress on Spondyloarthritides.

It’s an important topic, said Maxime Breban, MD, PhD, of Ambroise Paré Hospital in Paris, as flares can adversely affect patient outcomes. The absence of flares may also a useful measure of how well a patient is responding to treatment in clinical trials and whether a treatment can be tapered.

“There have been many ways to define flares in the past and there is no consensus,” he observed.

Although the Assessment of Spondyloarthritis International Society (ASAS) devised 12 preliminary definitions of flare in 2016, “these were not that good when we moved to patients,” Dr. Breban suggested.

The ASAS definitions were based on patient vignettes, he explained, and used a combination of variables from the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), a visual analog scale (VAS) of pain, and the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP).

The study that Dr. Breban presented looked at the performance of the ASAS preliminary definitions of axSpA flares in a real-life patient population, as well as prospectively determining how variations in BASDAI and VAS pain were associated with patient-perceived flares of disease.

A total of 99 patients took part in the study, recruited through a secure e-health platform called SPONDY+. Once a week, patients completed the BASDAI questionnaire and the pain VAS, and stated whether their disease had flared in the past week.

Receiver operating characteristic (ROC) curves were calculated to see how well the BASDAI and pain VAS identified patients who were experiencing a flare or had a recently resolved flare of axSpA.

Dr. Breban reported that variation in the BASDAI “appears a suitable variable to monitor the occurrence and resolution of patient-reported flare in axial spondylarthritis.”

In predicting a flare, the area under the curve (AUC) was significantly higher for the change in BASDAI than for the change in pain VAS, at a respective 0.81 and 0.77 (P = .01). However, both variables were similarly accurate in predicting the resolution of a flare, with respective AUCs of 0.78 and 0.80 (P = .3).

A 0.22-point increase in BASDAI was reported to be the best balance between sensitivity (70%) and specificity (79%) for a flare. However, this is “outside of what is possible within a test–retest situation,” Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, said during discussion.

Dr. van der Heijde told Dr. Breban: “I understand that that comes out of your data, that that’s the best combination for sensitivity and specificity, but the next step is to decide if that makes sense.”

The ROC curves that Dr. Breban presented showed the range of sensitivities and specificities that could be achieved. If the specificity was increased to be 90% or higher, the specificity fell to 55%, with the change in BASDAI being an increase of 0.8 points. Conversely, bringing the sensitivity above 90% meant the specificity dropped to 39% and the change in BASDAI was a decrease of 0.1 point.

“So that means you can choose whatever you want as a cutoff,” Dr. Breban said. It depends on what you are aiming to do. “If you want to identify a flare, you can increase sensitivity, or specificity, according to what your purpose is,” he suggested.

“The next step, of course, is what to choose as a flare. Then it depends on how you want to use a flare if you want to use a flare to change the treatment,” agreed Dr. van der Heijde. “That was why, in the ASAS group, it was decided to have a high specificity so that you are not changing treatment all the time.”

In the data that Dr. Breban presented, the ASAS preliminary definitions were highly specific but lacked sensitivity. None of the ASAS definitions yielded sensitivity values higher than 37%, whereas specificity was higher than 95% for all of them.

The study’s design did not allow researchers to test the ASDAS-CRP as a definition of flare in its real-world patient sample. Thus, it is looking only at the patient’s perspective on flare, and there is a “huge discrepancy” between patient and physician-reported disease activity, Dr. van der Heijde noted. “So, I think before using your data to really choose the flare definition, I think we need to take it all into account.”

Maxime Dougados, MD, PhD, of Cochin Hospital in Paris, who has been “deeply involved in the elaboration of the definition of flare” added his thoughts: “Flare means for me, not a status, but a change,” he observed.

But if the aim of treating people with axSpA is to achieve a good or acceptable state of health, he questioned whether work should be continued to define the concept of a flare.

The definition of a flare was conceived for use in clinical trials mainly, Dr. van der Heijde noted. It helped to assess how changes in treatment might affect the outcomes of patients. In clinical practice, especially now with treat-to-target gaining more and more traction in axSpA, she agreed that perhaps the goal should be to focus more on the health status of patients.

Dr. Breban acknowledged that the SPONDY+ platform has been developed by bepatient with support from Merck Sharp & Dohme. No other disclosures were made.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

Interleukin (IL)–23 inhibition may still have a role to play in the treatment of patients with axial spondyloarthritis (SpA), suggests research presented at the 12th International Congress on Spondyloarthritides.

There is a strong rationale for using IL-23 inhibitors in patients with axial SpA, and the IL-23/IL-17 axis has been proposed as a critical player in the pathophysiology of the disease. But around 2018 it became clear from randomized, controlled trials that IL-23 inhibition was ineffective at improving key clinical outcomes, at least in patients with axial disease.

Although the overall results of a systematic review and meta-analysis that was presented at the meeting corroborated the negative results seen with IL-23–inhibiting agents in clinical trials, there were some data showing benefits of the IL-23 inhibitor risankizumab on secondary outcomes in one trial.

To look at the available evidence, Louise Vanhoutte, a 2nd-year internal medicine student at University Hospitals Leuven (Belgium) worked under the guidance of Rik Lories, MD, PhD, head of the division of rheumatology at University Hospitals Leuven. Together they searched known databases for randomized, controlled trials investigating the use of IL-23 and IL-17 inhibitors for the treatment of adults with axial SpA or psoriatic arthritis. Studies could be either phase 2 or phase 3, but had to have included a placebo and used the ASAS40 (40% Improvement in Assessment of SpondyloArthritis International Society Response criteria), ASAS20, Bath Ankylosing Spondylitis Disease Activity Index, or SPARCC (Spondyloarthritis Research Consortium of Canada) index score to assess outcomes.

The systematic review whittled the number of clinical trials in the meta-analysis to 12, which concerned the use of ustekinumab, an IL-12/23 inhibitor, and risankizumab, along with two IL-17 inhibitors, ixekizumab and secukinumab. Data for the IL-23 inhibitors guselkumab and tildrakizumab were not available.

“To no surprise, Forest plots showed that there was a lack of efficacy for IL-23 agents in the treatment of axial spondyloarthritis and a superior efficacy for IL-17 inhibitors in the treatment of axial spondyloarthritis,” Ms. Vanhoutte reported.

The respective odds ratios for IL-23 and IL-17 inhibitors in getting patients to meet ASAS40 response criteria in comparison to baseline were 1.51 (95% confidence interval, 0.98-2.31) and 2.54 (95% CI, 2.02-3.19).

“Does this mean it is a dead-end street for all IL-23 inhibition?” she asked. Not necessarily. In the meta-analysis, not only did risankizumab lower the Ankylosing Spondylitis Disease Activity Score based on C-reactive protein (ASDAS-CRP) by a mean difference (MD) of –0.30 (95% CI, –0.41 to –0.19) from baseline values, but it also led to statistically significant reductions in SPARCC index score for the spine (MD, –3.10; 95% CI, –4.50 to –1.70) and high-sensitivity CRP (MD, –2.10; 95% CI, –2.56 to –1.64). The risankizumab findings might suggest there are potential disease-modifying properties for specifically targeting IL-23p19. There could also be a window of opportunity to use IL-23 inhibitors earlier.

“These are only results from one randomized, controlled trial in a small sample size where outcomes were reported as medians and interquartile ranges, so they had to be converted to means and standard deviations to have an odds ratio in the end,” she explained.

“Also, these were results from a radiographic axial spondyloarthritis population and not a nonradiographic axial spondyloarthritis population,” she added.

While that might limit the interpretation of the findings, “what we see here is both reduction in inflammation and reduction in structural disease progression as [measured] by SPARCC,” Ms. Vanhoutte said.

“Since IL-23 is an upstream molecule from IL-17 it’s probable that IL-23 is present in the prephase of the disease, in a prephase inflammation state,” she hypothesized. “This is especially interesting because there are very few randomized, controlled trials that examine therapeutic agents in nonradiographic axial spondyloarthritis,” she observed. Looking at IL-23 in radiographic, or established, disease therefore may not be as useful.

“I’m thinking you’re making actually a very important point for us,” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center.

“We are discussing whether or not IL-23 is important in inhibiting the disease activity of patients with axial spondyloarthritis, and we are surprised that it is not shown in RCTs.

“Why is it completely ineffective in axial spondyloarthritis? You show us that that is probably not the case,” Dr. Landewé suggested.

“What you make very clear here is that indeed there is some efficacy, and from a pathophysiological way of thinking it might be slightly different as compared with what most clinicians nowadays think.”

The study had no specific funding, and no disclosures were reported.

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

The European Medicines Agency’s Committee for Medicinal Products for Human Use recommended marketing authorization this week for two new adalimumab biosimilars, Hukyndra and Libmyris.

The biosimilars, both developed by STADA Arzneimittel AG, will be available as a 40-mg solution for injection in a pre-filled syringe and pre-filled pen and 80-mg solution for injection in a pre-filled syringe. Both biosimilars will have 15 indications:

• rheumatoid arthritis
• polyarticular juvenile idiopathic arthritis
• enthesitis-related arthritis
• ankylosing spondylitis
• axial spondyloarthritis without radiographic evidence of ankylosing spondylitis
• psoriatic arthritis
• chronic plaque psoriasis (adults and children)
• hidradenitis suppurativa
• Crohn’s disease (adults and children)
• ulcerative colitis (adults and children)
• uveitis (adults and children)

Data show that both Hukyndra and Libmyris are highly similar to the reference product Humira (adalimumab), a monoclonal antibody to tumor necrosis factor alpha, and have comparable quality, safety, and efficacy.

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

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

Better retention and remission rates with tumor necrosis factor inhibitors (TNFi) have been observed in patients with spondyloarthritis (SpA) who were also treated with a conventional synthetic disease-modifying antirheumatic drug (csDMARD) rather than monotherapy.

Data from the EuroSpA Research Collaboration have shown that 82% of patients who received TNFi and csDMARD cotherapy were still taking their TNFi at 1 year versus 79% of those who were taking the biologic alone (P < .001).

Combination therapy led to remission in 21.8%, compared with TNFi monotherapy at 19.5% (P < .0001), with rates of remission according to Ankylosing Spondylitis Disease Activity Score <1.3 (23.7% vs. 21.8%, P = .011) and Bath Ankylosing Spondylitis Disease Activity Index <2 (5.9% vs. 7.7%, P < .0001) also favoring the cotherapy group.

“We did see a considerable heterogeneity across the countries in this study, both in the use of csDMARD therapy and in the TNF [inhibitor] retention,” Michael J. Nissen, MBBS, FRACP, MD, a rheumatologist at the University of Geneva, said in an oral abstract presentation at the 12th International Congress on Spondyloarthritides.

“Overall, the 1-year TNFi retention was better with cotherapy, particularly in countries in the Scandinavian region and Switzerland,” Dr. Nissen observed.

“The csDMARD cotherapy significantly improved remission; we could perhaps argue whether these small differences are clinically meaningful, but they were highly significant in the study.”
 

Why look at csDMARD and TNFi cotherapy?

European guidelines suggest that csDMARDs are not that useful for treating people with SpA, stating that they should not be used in axial disease and used only as monotherapy in those with peripheral disease.

“Nevertheless, these medications are often used, which begs us to ask the question why is that the case?” Dr. Nissen said.

As previous work by Dr. Nissen and others had suggested that there might be a benefit of combining a csDMARD and a TNFi, the aim was to build upon this and see if looking at a very large patient population might be able to provide some clear answers.

The analysis included data from 13 European registries and more than 24,000 patients who had started their first TNFi between 2006 and 2017. The mean age of the study population was 42.5 years, and 58% were male, with an average disease duration of 5.9 years. Nearly one-third of patients were receiving comedication with a csDMARD, although this ranged from 13.5% to 71.2% depending on the country.

The most frequently used TNFi were adalimumab (31% of patients overall), etanercept (24%), and infliximab (25%), and the most-used csDMARDs were methotrexate (56%) and sulfasalazine (45%).

The effectiveness of treatment in achieving clinical remission was examined according to the TNFi used and for the use of csDMARDs.

“We found that sulfasalazine and methotrexate were similarly effective in terms of improving outcomes in addition to a TNF inhibitor,” Dr. Nissen said. For example, the adjusted odds ratios for using sulfasalazine or methotrexate with infliximab were a respective 1.32 and 1.37, and the aORs for uses these specific csDMARDs with etanercept were 1.38 and 1.35.

The researchers reported finding significantly higher aORs if both sulfasalazine and methotrexate were used with a TNFi (1.67 for any TNFi, 1.95 for infliximab, 1.45 foretanercept, and 1.85 for adalimumab).

This perhaps suggests “there’s some role for combining csDMARDs to have an even greater effect,” Dr. Nissen put forward.
 

A ‘very provocative conclusion’

That’s “a very provocative conclusion” commented Robert Landewé, MD, PhD, of Amsterdam University Medical Center who chaired the sessions. “You can see it by the [number] of people that want to ask questions.”

Désirée van der Heijde, MD, PhD, of Leiden (the Netherlands) University Medical Center, commented these data were “timely as we are updating the ASAS/EULAR [Assessment of SpondyloArthritis international Society/European Alliance of Associations for Rheumatology] recommendations at the moment.” She queried, however, if the differences were clinically significant.

“I think if you have a database of 24,000 patients, highly, statistically significant doesn’t tell me a lot. So, I want to look at the clinical meaning of the differences. So, if you have a 2% difference in retention rate, is that worth prescribing comedication?” Dr. van der Heijde said.

“I think you’re absolutely right,” Dr. Nissen responded. “We’re obviously going to find highly significant differences with such a big patient group.” While the small statistical differences seen may not look very clinically relevant at face value, they could provide some guidance for clinical decision making.

“It may alter our approach if that patient is already on a csDMARD and has peripheral disease; perhaps there’s tendency to then to keep that csDMARD rather than then stopping it and switching to a biologic agent,” Dr. Nissen argued. It’s a topic that has been debated for some time, he added, and further study is needed, but “I think it helps give a little bit more clarity to the idea.”

Another point of discussion was the proportion of patients who had “pure axial disease.” More patients in the comedication group had peripheral disease, Dr. van der Heijde pointed out, “that’s also where we expect to see the differences.”

Further research is needed, but there doesn’t seem to be any impact in terms of the effect on retention, Dr. Nissen said, “but it’s a little bit harder to interpret for efficacy.”

Confounding by indication was another issued raised, which “is very difficult to control for in this type of study,” Dr. Nissen said.

“The hope is that you have a big enough population” so this doesn’t matter, but as is the nature there were lots of missing data that would have been useful to have and adjust for, such as psoriasis and smoking status. There was also no adjustment for the number of patient visits, as it’s very different from registry to registry.

Dr. Nissen disclosed grant/research support from AbbVie and Novartis. He also acknowledged acting as a consultant or speaker for AbbVie, Celgene, Janssen, Eli Lilly, Novartis, and Pfizer.

A new study rebuts the conventional rheumatology wisdom about ankylosing spondylitis (AS) by reporting that actually there’s no gender gap in the prevalence of the disease. Researchers found no statistically significant difference in rates between men and women based on an analysis of military medical records.

feellife/Thinkstock

“Our findings challenge the widely held belief that AS in the U.S. occurs substantially more frequently in males than females,” the study authors, led by data scientist D. Alan Nelson, PhD, of Stanford (Calif.) University, wrote in a study published Aug. 30 in Arthritis Care & Research.

The researchers launched the study to fill a gap in knowledge regarding case rates by gender. “The incidence of AS in the U.S. has been understudied and incompletely characterized,” they wrote.

Even though AS is fairly common, affecting an estimated 1% of the American adult population (2.5 million people), only one published population study has examined rates by gender in the United States. That study tracked cases in Minnesota’s Olmsted County during 1980-2009 and found that the ratio of cases in men vs. women was 3.8:1, which was “consistent with more recent estimates” at the time.

However, the population in that study in 1980 was 100% White, the authors of the new study note. A Canadian study that tracked an Ontario population from 1995 to 2010, meanwhile, suggested that AS rates among women were rising and the gender gap was shrinking. AS rates as a whole also nearly tripled, possibly because of more awareness.

For the new study, researchers retrospectively tracked 728,556 members of the U.S. military who underwent guideline-directed screening for back pain during 2014-2017. The study population was about 68% White, 22% Black, 5% Asian or Pacific Islander, and the remainder were other races or unknown. About 85% were male.

The subjects were monitored for a mean of 2.21 years, and 438 (0.06%) were diagnosed with AS at least once over that period.

The researchers found that the AS rates among males vs. females were similar (incidence rate ratio, 1.16; P = .23; adjusted odds ratio, 0.79; 95% confidence interval, 0.61-1.02; P = .072).

The researchers also found that Whites were more likely to develop AS than Blacks (aOR, 1.39; 95% CI, 1.01-1.66; P = .04).

The risk of AS increased with age, the researchers reported, with the odds growing sevenfold in the 45-and-older population vs. the under-24 population (aOR, 7.3; 95% CI, 5.7-10.3; P < .001).

The researchers noted that their study examined a more diverse population than the earlier Minnesota study. It’s also possible that the results of the two studies differed because of differences in definitions of AS diagnosis or imprecision in diagnosis codes, they wrote.

The researchers added that “the finding of a 1.21 male-female prevalence ratio of AS in the Canadian Ontario study was also generally consistent with our findings. Similar to our study population, the Canadian population was racially more diverse than the Olmsted study population at the times of both studies.”

Some limitations of the study include the fact that the military population is not a random sample and may have low rates of AS. “It is highly likely that most clinically evident cases of AS would have been screened out prior to enrollment in the military service,” they wrote. “Differences between military service members and the general population may explain why we observed a different association between AS incidence and age in comparison to that reported by prior studies. The increasing risk of AS with adult age that we observed could reflect selective discharge patterns related to very early symptoms of AS in this population.”

The study was funded in part by a grant from the Spondylitis Association of America. No information about potential conflicts of interest was provided in the manuscript.

A new study rebuts the conventional rheumatology wisdom about ankylosing spondylitis (AS) by reporting that actually there’s no gender gap in the prevalence of the disease. Researchers found no statistically significant difference in rates between men and women based on an analysis of military medical records.

feellife/Thinkstock

“Our findings challenge the widely held belief that AS in the U.S. occurs substantially more frequently in males than females,” the study authors, led by data scientist D. Alan Nelson, PhD, of Stanford (Calif.) University, wrote in a study published Aug. 30 in Arthritis Care & Research.

The researchers launched the study to fill a gap in knowledge regarding case rates by gender. “The incidence of AS in the U.S. has been understudied and incompletely characterized,” they wrote.

Even though AS is fairly common, affecting an estimated 1% of the American adult population (2.5 million people), only one published population study has examined rates by gender in the United States. That study tracked cases in Minnesota’s Olmsted County during 1980-2009 and found that the ratio of cases in men vs. women was 3.8:1, which was “consistent with more recent estimates” at the time.

However, the population in that study in 1980 was 100% White, the authors of the new study note. A Canadian study that tracked an Ontario population from 1995 to 2010, meanwhile, suggested that AS rates among women were rising and the gender gap was shrinking. AS rates as a whole also nearly tripled, possibly because of more awareness.

For the new study, researchers retrospectively tracked 728,556 members of the U.S. military who underwent guideline-directed screening for back pain during 2014-2017. The study population was about 68% White, 22% Black, 5% Asian or Pacific Islander, and the remainder were other races or unknown. About 85% were male.

The subjects were monitored for a mean of 2.21 years, and 438 (0.06%) were diagnosed with AS at least once over that period.

The researchers found that the AS rates among males vs. females were similar (incidence rate ratio, 1.16; P = .23; adjusted odds ratio, 0.79; 95% confidence interval, 0.61-1.02; P = .072).

The researchers also found that Whites were more likely to develop AS than Blacks (aOR, 1.39; 95% CI, 1.01-1.66; P = .04).

The risk of AS increased with age, the researchers reported, with the odds growing sevenfold in the 45-and-older population vs. the under-24 population (aOR, 7.3; 95% CI, 5.7-10.3; P < .001).

The researchers noted that their study examined a more diverse population than the earlier Minnesota study. It’s also possible that the results of the two studies differed because of differences in definitions of AS diagnosis or imprecision in diagnosis codes, they wrote.

The researchers added that “the finding of a 1.21 male-female prevalence ratio of AS in the Canadian Ontario study was also generally consistent with our findings. Similar to our study population, the Canadian population was racially more diverse than the Olmsted study population at the times of both studies.”

Some limitations of the study include the fact that the military population is not a random sample and may have low rates of AS. “It is highly likely that most clinically evident cases of AS would have been screened out prior to enrollment in the military service,” they wrote. “Differences between military service members and the general population may explain why we observed a different association between AS incidence and age in comparison to that reported by prior studies. The increasing risk of AS with adult age that we observed could reflect selective discharge patterns related to very early symptoms of AS in this population.”

The study was funded in part by a grant from the Spondylitis Association of America. No information about potential conflicts of interest was provided in the manuscript.

A new study rebuts the conventional rheumatology wisdom about ankylosing spondylitis (AS) by reporting that actually there’s no gender gap in the prevalence of the disease. Researchers found no statistically significant difference in rates between men and women based on an analysis of military medical records.

feellife/Thinkstock

“Our findings challenge the widely held belief that AS in the U.S. occurs substantially more frequently in males than females,” the study authors, led by data scientist D. Alan Nelson, PhD, of Stanford (Calif.) University, wrote in a study published Aug. 30 in Arthritis Care & Research.

The researchers launched the study to fill a gap in knowledge regarding case rates by gender. “The incidence of AS in the U.S. has been understudied and incompletely characterized,” they wrote.

Even though AS is fairly common, affecting an estimated 1% of the American adult population (2.5 million people), only one published population study has examined rates by gender in the United States. That study tracked cases in Minnesota’s Olmsted County during 1980-2009 and found that the ratio of cases in men vs. women was 3.8:1, which was “consistent with more recent estimates” at the time.

However, the population in that study in 1980 was 100% White, the authors of the new study note. A Canadian study that tracked an Ontario population from 1995 to 2010, meanwhile, suggested that AS rates among women were rising and the gender gap was shrinking. AS rates as a whole also nearly tripled, possibly because of more awareness.

For the new study, researchers retrospectively tracked 728,556 members of the U.S. military who underwent guideline-directed screening for back pain during 2014-2017. The study population was about 68% White, 22% Black, 5% Asian or Pacific Islander, and the remainder were other races or unknown. About 85% were male.

The subjects were monitored for a mean of 2.21 years, and 438 (0.06%) were diagnosed with AS at least once over that period.

The researchers found that the AS rates among males vs. females were similar (incidence rate ratio, 1.16; P = .23; adjusted odds ratio, 0.79; 95% confidence interval, 0.61-1.02; P = .072).

The researchers also found that Whites were more likely to develop AS than Blacks (aOR, 1.39; 95% CI, 1.01-1.66; P = .04).

The risk of AS increased with age, the researchers reported, with the odds growing sevenfold in the 45-and-older population vs. the under-24 population (aOR, 7.3; 95% CI, 5.7-10.3; P < .001).

The researchers noted that their study examined a more diverse population than the earlier Minnesota study. It’s also possible that the results of the two studies differed because of differences in definitions of AS diagnosis or imprecision in diagnosis codes, they wrote.

The researchers added that “the finding of a 1.21 male-female prevalence ratio of AS in the Canadian Ontario study was also generally consistent with our findings. Similar to our study population, the Canadian population was racially more diverse than the Olmsted study population at the times of both studies.”

Some limitations of the study include the fact that the military population is not a random sample and may have low rates of AS. “It is highly likely that most clinically evident cases of AS would have been screened out prior to enrollment in the military service,” they wrote. “Differences between military service members and the general population may explain why we observed a different association between AS incidence and age in comparison to that reported by prior studies. The increasing risk of AS with adult age that we observed could reflect selective discharge patterns related to very early symptoms of AS in this population.”

The study was funded in part by a grant from the Spondylitis Association of America. No information about potential conflicts of interest was provided in the manuscript.