Ankylosing spondylitis

The rheumatologist of the future will see patients who have been assessed and triaged with artificial intelligence utilizing data from remote kiosk-placed ultrasound scanners and physician-directed algorithms. Practices will be broadly fueled by AI, which will screen charts, produce notes, handle prior authorizations and insurance issues, aid in earlier diagnoses, find patients for clinical trials, and maybe even suggest the next best therapy for individual patients.

Such is the future envisioned by Alvin F. Wells, MD, PhD, and John J. Cush, MD, who discussed the current and forthcoming reach of AI — and their own uses of it — at the 2024 Rheumatology Winter Clinical Symposium.

“We’re not at the stage where ChatGPT and AI can tell us what the next best therapy is, but we’re getting there,” said Dr. Cush, a rheumatologist based in Dallas and executive director of RheumNow.com. For now, he said, “AI affords us a truly big-time increase in efficiency. It helps you deal with your time constraints in managing information overload and task overload.”

Bruce Jancin/MDedge News

At a time when “PubMed doubles every 73 days ... and it’s getting harder and harder to stay abreast,” for example, new applications such as Scite, SciSpace, and Consensus can help curate, focus, and analyze the literature to match one’s own clinical interests. Such review tools are “just now getting into play and are evolving,” Dr. Cush said, noting that many but not all of them are based on ChatGPT, OpenAI’s chatbot that had a over 100 million users by January 2023 — just over a month after its version 3.5 was released.

For Dr. Wells, a rheumatologist and Midwest Region director in the department of rheumatology for the Advocate Health Medical Group in Franklin, Wisconsin, clinician-developed algorithms are helping his group assess patients — often remotely — and triage them to be seen fairly immediately by a rheumatologist versus in 4-6 weeks or in several months. “You can use AI to guide your access,” he said.

A patient “with a family history of RA, sed rate above 50, and osteopenia on x-rays” would be seen within a week, for example, while “another patient who’s had a [positive] ANA with no other symptoms, and maybe a family history, might be seen in 4-6 weeks,” said Dr. Wells, sharing his belief that “there is not a shortage of rheumatologists, [but a] shortage of using rheumatologists efficiently.”

Dr. Wells

AI for Improving Workflow

Current and future advances will enrich the intersection of AI and virtual medicine and improve outcomes and the rheumatologist-patient interaction, Dr. Wells said, pointing to research presented at the American College of Rheumatology (ACR) 2023 annual meeting on the use of computer vision technology for remotely assessing disease activity in rheumatoid arthritis (RA).

In the proof-of-concept “MeFisto” study, 28 patients with RA used an app that enabled computer vision inference of hand motion data. Upon recording, an algorithm tracked the mean degree change of joint angle on flexion and the mean time to maximal flexion for each joint.

The researchers found a strong correlation between flexion of the distal interphalangeal (DIP) joint and the Disease Activity Score in 28 joints, the Swollen Hand Joint Count, and the Tender Hand Joint Count. DIP flexion was found to be a significant predictor of low disease activity/remission and high disease activity, the researchers reported in their abstract.

“This blows you away — that a single camera on [one’s] smartphone can look at the manipulation of a hand … and that AI can tell me, there’s a chance this might be an inflammatory arthritis,” said Dr. Wells, noting that researchers are also developing ways to detect joint swelling in RA by AI.

AI can also be used for remote ultrasound scanning in RA, as evidenced by use of the ARTHUR system in Europe, he said. Developed by the Danish company ROPCA, the ARTHUR technology (Rheumatoid Arthritis Ultrasound Robot) interacts directly with the patient who has new joint pain or established RA to capture ultrasound images in grayscale and color flow of 11 joints per hand. AI analyzes the images and creates a report for the specialist.

“They’re trying to get a foothold in the US,” Dr. Wells said, sharing his prediction that similar technology will someday be seen not only in pharmacies but also — in support of equitable access — in locations such as grocery stores. “Again,” he said, “nothing will replace us. I’m taking all [such] information and saying, who needs to be seen in 7 days and who can wait.”
 

AI for Writing, for Improving Practice and Patient Care

To manage his “task overload,” Dr. Cush uses ChatGPT for jobs such as first drafts of articles and making PowerPoint slides. It must be used cautiously for medical writing, however, as inaccuracies and false data/fabricated information — some of which has been coined AI “hallucinations” — are not uncommon.

“It’s very good at manuscript drafts, at generating bibliographies … it can do systematic reviews, it can do network meta-analyses, and it can find trends and patterns that can very helpful when it comes to writing. But you have to know how it’s a tool, and how it can hurt you,” he said.

Researchers recently reported asking ChatGPT to write an editorial about “how AI may replace the rheumatologist in editorial writing,” Dr. Cush noted. ChatGPT was “very politically correct,” he quipped, because it wrote that AI is “a tool to help the rheumatologist, but not replace him.”

Publishers want to preserve human intelligence — critical thinking and the ability to interpret, for instance — and most of the top medical journals (those most often cited) have issued guidance on the use of generative AI. “One said AI can’t be attributed as an author because being an author carries with it accountability of the work, and AI can’t take responsibility,” Dr. Cush said. Journals also “are saying you can use AI but you have to be totally transparent about it … [how it’s used] has to be very well spelled out.”

In practice, chatbots can be used for summarizing medical records, drafting post-visit summaries, collecting patient feedback, reminding about vaccinations, and performing administrative functions. “It’s really limitless as to what chatbots can do,” Dr. Cush said. “The question is, [what is] really going to help you?”

Much of the research submitted for presentation at major rheumatology meetings over the years has had questionable real-world utility and value, he said. But in the future this will likely change. “Take the PsA [psoriatic arthritis] patient who hasn’t responded to methotrexate or apremilast [Otezla]. There are [so many] choices, and there really isn’t a clear one. Shouldn’t data guide us on whether an IL-23 is better than a JAK, or maybe a JAK preferred over a TNF for some reason?” Dr. Cush said. “That’s what we’re hoping will happen down the line.”

More realistic AI-guided clinical scenarios for now include the following: AI screens the chart of a 68-year-old with RA on methotrexate and etanercept who is following up, and retrieves pieces of history — an elevated C-reactive protein 3 months ago, for instance, and diverticulosis 5 years ago. “AI tells you, based on this, he may have active disease, and here are three medications covered by his insurance,” Dr. Wells said.

Or, in the case of a 58-year-old patient with RA who has scheduled a virtual follow-up visit after having been on methotrexate and hydroxychloroquine for 12 weeks, AI detects a low platelet count in her previsit labs and also sees that she received an MMR booster 5 weeks ago at a local CVS Minute Clinic. AI retrieves for the rheumatologist a review article about thrombocytopenic purpura after MMR vaccination.
 

AI for Drug Development, Clinical Trials

Dr. Cush is following with keen interest the integration of AI into the process of drug development, from drug discovery and biomarker evaluation to clinical trial efficiency and patient recruitment, as well as marketing. “A lot hasn’t been ‘rolled out’ or shown to us, but there’s a lot going on … everyone is investing,” he said. “The number one challenge is regulatory: How will the [Food and Drug Administration] handle AI-generated data sets or AI-generated or monitored trials?”

The FDA is working to ensure quality and utility of data and is rapidly “approving AI algorithms for use in medicine and healthcare,” he said.

AI’s ability to identify patients in populations can not only facilitate earlier diagnoses but can accelerate patient recruitment for clinical trials, Dr. Cush emphasized. He pointed to research presented at the ACR 2021 annual meeting in which a machine-learning algorithm was used with electronic health records in the United Kingdom to estimate the probability of a patient’s being diagnosed with axial spondyloarthritis (axSpA).

AI identified 89 best clinical predictors (out of 820 analyzed). When applying these predictors to the population, AI was able to differentiate patients with axSpA from healthy controls with a sensitivity of 75%, a specificity of 96%, and a positive predictive value of 81%. Such an application of AI “is ideal … It would make clinical trials more streamlined and productive,” he said.

The extent to which AI will lead to cost savings — in the pharmacology arena, for instance, or for Well’s medical group — is unknown, Dr. Cush and Dr. Wells said. And, of course, there are concerns about potential bias and abuse of AI. “The worry,” Dr. Cush said, “is, who’s watching?”

Dr. Wells disclosed that he has research support and has served as a member of advisory boards and/or speaker bureaus for 17 different pharmaceutical or medical technology companies. Dr. Cush disclosed relationships with AbbVie, Amgen, Bristol-Myers Squibb, Novartis, Sanofi, and UCB.

The rheumatologist of the future will see patients who have been assessed and triaged with artificial intelligence utilizing data from remote kiosk-placed ultrasound scanners and physician-directed algorithms. Practices will be broadly fueled by AI, which will screen charts, produce notes, handle prior authorizations and insurance issues, aid in earlier diagnoses, find patients for clinical trials, and maybe even suggest the next best therapy for individual patients.

Such is the future envisioned by Alvin F. Wells, MD, PhD, and John J. Cush, MD, who discussed the current and forthcoming reach of AI — and their own uses of it — at the 2024 Rheumatology Winter Clinical Symposium.

“We’re not at the stage where ChatGPT and AI can tell us what the next best therapy is, but we’re getting there,” said Dr. Cush, a rheumatologist based in Dallas and executive director of RheumNow.com. For now, he said, “AI affords us a truly big-time increase in efficiency. It helps you deal with your time constraints in managing information overload and task overload.”

Bruce Jancin/MDedge News

At a time when “PubMed doubles every 73 days ... and it’s getting harder and harder to stay abreast,” for example, new applications such as Scite, SciSpace, and Consensus can help curate, focus, and analyze the literature to match one’s own clinical interests. Such review tools are “just now getting into play and are evolving,” Dr. Cush said, noting that many but not all of them are based on ChatGPT, OpenAI’s chatbot that had a over 100 million users by January 2023 — just over a month after its version 3.5 was released.

For Dr. Wells, a rheumatologist and Midwest Region director in the department of rheumatology for the Advocate Health Medical Group in Franklin, Wisconsin, clinician-developed algorithms are helping his group assess patients — often remotely — and triage them to be seen fairly immediately by a rheumatologist versus in 4-6 weeks or in several months. “You can use AI to guide your access,” he said.

A patient “with a family history of RA, sed rate above 50, and osteopenia on x-rays” would be seen within a week, for example, while “another patient who’s had a [positive] ANA with no other symptoms, and maybe a family history, might be seen in 4-6 weeks,” said Dr. Wells, sharing his belief that “there is not a shortage of rheumatologists, [but a] shortage of using rheumatologists efficiently.”

Dr. Wells

AI for Improving Workflow

Current and future advances will enrich the intersection of AI and virtual medicine and improve outcomes and the rheumatologist-patient interaction, Dr. Wells said, pointing to research presented at the American College of Rheumatology (ACR) 2023 annual meeting on the use of computer vision technology for remotely assessing disease activity in rheumatoid arthritis (RA).

In the proof-of-concept “MeFisto” study, 28 patients with RA used an app that enabled computer vision inference of hand motion data. Upon recording, an algorithm tracked the mean degree change of joint angle on flexion and the mean time to maximal flexion for each joint.

The researchers found a strong correlation between flexion of the distal interphalangeal (DIP) joint and the Disease Activity Score in 28 joints, the Swollen Hand Joint Count, and the Tender Hand Joint Count. DIP flexion was found to be a significant predictor of low disease activity/remission and high disease activity, the researchers reported in their abstract.

“This blows you away — that a single camera on [one’s] smartphone can look at the manipulation of a hand … and that AI can tell me, there’s a chance this might be an inflammatory arthritis,” said Dr. Wells, noting that researchers are also developing ways to detect joint swelling in RA by AI.

AI can also be used for remote ultrasound scanning in RA, as evidenced by use of the ARTHUR system in Europe, he said. Developed by the Danish company ROPCA, the ARTHUR technology (Rheumatoid Arthritis Ultrasound Robot) interacts directly with the patient who has new joint pain or established RA to capture ultrasound images in grayscale and color flow of 11 joints per hand. AI analyzes the images and creates a report for the specialist.

“They’re trying to get a foothold in the US,” Dr. Wells said, sharing his prediction that similar technology will someday be seen not only in pharmacies but also — in support of equitable access — in locations such as grocery stores. “Again,” he said, “nothing will replace us. I’m taking all [such] information and saying, who needs to be seen in 7 days and who can wait.”
 

AI for Writing, for Improving Practice and Patient Care

To manage his “task overload,” Dr. Cush uses ChatGPT for jobs such as first drafts of articles and making PowerPoint slides. It must be used cautiously for medical writing, however, as inaccuracies and false data/fabricated information — some of which has been coined AI “hallucinations” — are not uncommon.

“It’s very good at manuscript drafts, at generating bibliographies … it can do systematic reviews, it can do network meta-analyses, and it can find trends and patterns that can very helpful when it comes to writing. But you have to know how it’s a tool, and how it can hurt you,” he said.

Researchers recently reported asking ChatGPT to write an editorial about “how AI may replace the rheumatologist in editorial writing,” Dr. Cush noted. ChatGPT was “very politically correct,” he quipped, because it wrote that AI is “a tool to help the rheumatologist, but not replace him.”

Publishers want to preserve human intelligence — critical thinking and the ability to interpret, for instance — and most of the top medical journals (those most often cited) have issued guidance on the use of generative AI. “One said AI can’t be attributed as an author because being an author carries with it accountability of the work, and AI can’t take responsibility,” Dr. Cush said. Journals also “are saying you can use AI but you have to be totally transparent about it … [how it’s used] has to be very well spelled out.”

In practice, chatbots can be used for summarizing medical records, drafting post-visit summaries, collecting patient feedback, reminding about vaccinations, and performing administrative functions. “It’s really limitless as to what chatbots can do,” Dr. Cush said. “The question is, [what is] really going to help you?”

Much of the research submitted for presentation at major rheumatology meetings over the years has had questionable real-world utility and value, he said. But in the future this will likely change. “Take the PsA [psoriatic arthritis] patient who hasn’t responded to methotrexate or apremilast [Otezla]. There are [so many] choices, and there really isn’t a clear one. Shouldn’t data guide us on whether an IL-23 is better than a JAK, or maybe a JAK preferred over a TNF for some reason?” Dr. Cush said. “That’s what we’re hoping will happen down the line.”

More realistic AI-guided clinical scenarios for now include the following: AI screens the chart of a 68-year-old with RA on methotrexate and etanercept who is following up, and retrieves pieces of history — an elevated C-reactive protein 3 months ago, for instance, and diverticulosis 5 years ago. “AI tells you, based on this, he may have active disease, and here are three medications covered by his insurance,” Dr. Wells said.

Or, in the case of a 58-year-old patient with RA who has scheduled a virtual follow-up visit after having been on methotrexate and hydroxychloroquine for 12 weeks, AI detects a low platelet count in her previsit labs and also sees that she received an MMR booster 5 weeks ago at a local CVS Minute Clinic. AI retrieves for the rheumatologist a review article about thrombocytopenic purpura after MMR vaccination.
 

AI for Drug Development, Clinical Trials

Dr. Cush is following with keen interest the integration of AI into the process of drug development, from drug discovery and biomarker evaluation to clinical trial efficiency and patient recruitment, as well as marketing. “A lot hasn’t been ‘rolled out’ or shown to us, but there’s a lot going on … everyone is investing,” he said. “The number one challenge is regulatory: How will the [Food and Drug Administration] handle AI-generated data sets or AI-generated or monitored trials?”

The FDA is working to ensure quality and utility of data and is rapidly “approving AI algorithms for use in medicine and healthcare,” he said.

AI’s ability to identify patients in populations can not only facilitate earlier diagnoses but can accelerate patient recruitment for clinical trials, Dr. Cush emphasized. He pointed to research presented at the ACR 2021 annual meeting in which a machine-learning algorithm was used with electronic health records in the United Kingdom to estimate the probability of a patient’s being diagnosed with axial spondyloarthritis (axSpA).

AI identified 89 best clinical predictors (out of 820 analyzed). When applying these predictors to the population, AI was able to differentiate patients with axSpA from healthy controls with a sensitivity of 75%, a specificity of 96%, and a positive predictive value of 81%. Such an application of AI “is ideal … It would make clinical trials more streamlined and productive,” he said.

The extent to which AI will lead to cost savings — in the pharmacology arena, for instance, or for Well’s medical group — is unknown, Dr. Cush and Dr. Wells said. And, of course, there are concerns about potential bias and abuse of AI. “The worry,” Dr. Cush said, “is, who’s watching?”

Dr. Wells disclosed that he has research support and has served as a member of advisory boards and/or speaker bureaus for 17 different pharmaceutical or medical technology companies. Dr. Cush disclosed relationships with AbbVie, Amgen, Bristol-Myers Squibb, Novartis, Sanofi, and UCB.

The rheumatologist of the future will see patients who have been assessed and triaged with artificial intelligence utilizing data from remote kiosk-placed ultrasound scanners and physician-directed algorithms. Practices will be broadly fueled by AI, which will screen charts, produce notes, handle prior authorizations and insurance issues, aid in earlier diagnoses, find patients for clinical trials, and maybe even suggest the next best therapy for individual patients.

Such is the future envisioned by Alvin F. Wells, MD, PhD, and John J. Cush, MD, who discussed the current and forthcoming reach of AI — and their own uses of it — at the 2024 Rheumatology Winter Clinical Symposium.

“We’re not at the stage where ChatGPT and AI can tell us what the next best therapy is, but we’re getting there,” said Dr. Cush, a rheumatologist based in Dallas and executive director of RheumNow.com. For now, he said, “AI affords us a truly big-time increase in efficiency. It helps you deal with your time constraints in managing information overload and task overload.”

Bruce Jancin/MDedge News

At a time when “PubMed doubles every 73 days ... and it’s getting harder and harder to stay abreast,” for example, new applications such as Scite, SciSpace, and Consensus can help curate, focus, and analyze the literature to match one’s own clinical interests. Such review tools are “just now getting into play and are evolving,” Dr. Cush said, noting that many but not all of them are based on ChatGPT, OpenAI’s chatbot that had a over 100 million users by January 2023 — just over a month after its version 3.5 was released.

For Dr. Wells, a rheumatologist and Midwest Region director in the department of rheumatology for the Advocate Health Medical Group in Franklin, Wisconsin, clinician-developed algorithms are helping his group assess patients — often remotely — and triage them to be seen fairly immediately by a rheumatologist versus in 4-6 weeks or in several months. “You can use AI to guide your access,” he said.

A patient “with a family history of RA, sed rate above 50, and osteopenia on x-rays” would be seen within a week, for example, while “another patient who’s had a [positive] ANA with no other symptoms, and maybe a family history, might be seen in 4-6 weeks,” said Dr. Wells, sharing his belief that “there is not a shortage of rheumatologists, [but a] shortage of using rheumatologists efficiently.”

Dr. Wells

AI for Improving Workflow

Current and future advances will enrich the intersection of AI and virtual medicine and improve outcomes and the rheumatologist-patient interaction, Dr. Wells said, pointing to research presented at the American College of Rheumatology (ACR) 2023 annual meeting on the use of computer vision technology for remotely assessing disease activity in rheumatoid arthritis (RA).

In the proof-of-concept “MeFisto” study, 28 patients with RA used an app that enabled computer vision inference of hand motion data. Upon recording, an algorithm tracked the mean degree change of joint angle on flexion and the mean time to maximal flexion for each joint.

The researchers found a strong correlation between flexion of the distal interphalangeal (DIP) joint and the Disease Activity Score in 28 joints, the Swollen Hand Joint Count, and the Tender Hand Joint Count. DIP flexion was found to be a significant predictor of low disease activity/remission and high disease activity, the researchers reported in their abstract.

“This blows you away — that a single camera on [one’s] smartphone can look at the manipulation of a hand … and that AI can tell me, there’s a chance this might be an inflammatory arthritis,” said Dr. Wells, noting that researchers are also developing ways to detect joint swelling in RA by AI.

AI can also be used for remote ultrasound scanning in RA, as evidenced by use of the ARTHUR system in Europe, he said. Developed by the Danish company ROPCA, the ARTHUR technology (Rheumatoid Arthritis Ultrasound Robot) interacts directly with the patient who has new joint pain or established RA to capture ultrasound images in grayscale and color flow of 11 joints per hand. AI analyzes the images and creates a report for the specialist.

“They’re trying to get a foothold in the US,” Dr. Wells said, sharing his prediction that similar technology will someday be seen not only in pharmacies but also — in support of equitable access — in locations such as grocery stores. “Again,” he said, “nothing will replace us. I’m taking all [such] information and saying, who needs to be seen in 7 days and who can wait.”
 

AI for Writing, for Improving Practice and Patient Care

To manage his “task overload,” Dr. Cush uses ChatGPT for jobs such as first drafts of articles and making PowerPoint slides. It must be used cautiously for medical writing, however, as inaccuracies and false data/fabricated information — some of which has been coined AI “hallucinations” — are not uncommon.

“It’s very good at manuscript drafts, at generating bibliographies … it can do systematic reviews, it can do network meta-analyses, and it can find trends and patterns that can very helpful when it comes to writing. But you have to know how it’s a tool, and how it can hurt you,” he said.

Researchers recently reported asking ChatGPT to write an editorial about “how AI may replace the rheumatologist in editorial writing,” Dr. Cush noted. ChatGPT was “very politically correct,” he quipped, because it wrote that AI is “a tool to help the rheumatologist, but not replace him.”

Publishers want to preserve human intelligence — critical thinking and the ability to interpret, for instance — and most of the top medical journals (those most often cited) have issued guidance on the use of generative AI. “One said AI can’t be attributed as an author because being an author carries with it accountability of the work, and AI can’t take responsibility,” Dr. Cush said. Journals also “are saying you can use AI but you have to be totally transparent about it … [how it’s used] has to be very well spelled out.”

In practice, chatbots can be used for summarizing medical records, drafting post-visit summaries, collecting patient feedback, reminding about vaccinations, and performing administrative functions. “It’s really limitless as to what chatbots can do,” Dr. Cush said. “The question is, [what is] really going to help you?”

Much of the research submitted for presentation at major rheumatology meetings over the years has had questionable real-world utility and value, he said. But in the future this will likely change. “Take the PsA [psoriatic arthritis] patient who hasn’t responded to methotrexate or apremilast [Otezla]. There are [so many] choices, and there really isn’t a clear one. Shouldn’t data guide us on whether an IL-23 is better than a JAK, or maybe a JAK preferred over a TNF for some reason?” Dr. Cush said. “That’s what we’re hoping will happen down the line.”

More realistic AI-guided clinical scenarios for now include the following: AI screens the chart of a 68-year-old with RA on methotrexate and etanercept who is following up, and retrieves pieces of history — an elevated C-reactive protein 3 months ago, for instance, and diverticulosis 5 years ago. “AI tells you, based on this, he may have active disease, and here are three medications covered by his insurance,” Dr. Wells said.

Or, in the case of a 58-year-old patient with RA who has scheduled a virtual follow-up visit after having been on methotrexate and hydroxychloroquine for 12 weeks, AI detects a low platelet count in her previsit labs and also sees that she received an MMR booster 5 weeks ago at a local CVS Minute Clinic. AI retrieves for the rheumatologist a review article about thrombocytopenic purpura after MMR vaccination.
 

AI for Drug Development, Clinical Trials

Dr. Cush is following with keen interest the integration of AI into the process of drug development, from drug discovery and biomarker evaluation to clinical trial efficiency and patient recruitment, as well as marketing. “A lot hasn’t been ‘rolled out’ or shown to us, but there’s a lot going on … everyone is investing,” he said. “The number one challenge is regulatory: How will the [Food and Drug Administration] handle AI-generated data sets or AI-generated or monitored trials?”

The FDA is working to ensure quality and utility of data and is rapidly “approving AI algorithms for use in medicine and healthcare,” he said.

AI’s ability to identify patients in populations can not only facilitate earlier diagnoses but can accelerate patient recruitment for clinical trials, Dr. Cush emphasized. He pointed to research presented at the ACR 2021 annual meeting in which a machine-learning algorithm was used with electronic health records in the United Kingdom to estimate the probability of a patient’s being diagnosed with axial spondyloarthritis (axSpA).

AI identified 89 best clinical predictors (out of 820 analyzed). When applying these predictors to the population, AI was able to differentiate patients with axSpA from healthy controls with a sensitivity of 75%, a specificity of 96%, and a positive predictive value of 81%. Such an application of AI “is ideal … It would make clinical trials more streamlined and productive,” he said.

The extent to which AI will lead to cost savings — in the pharmacology arena, for instance, or for Well’s medical group — is unknown, Dr. Cush and Dr. Wells said. And, of course, there are concerns about potential bias and abuse of AI. “The worry,” Dr. Cush said, “is, who’s watching?”

Dr. Wells disclosed that he has research support and has served as a member of advisory boards and/or speaker bureaus for 17 different pharmaceutical or medical technology companies. Dr. Cush disclosed relationships with AbbVie, Amgen, Bristol-Myers Squibb, Novartis, Sanofi, and UCB.

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

A Danish study showing that about half of patients with newly diagnosed inflammatory bowel disease (IBD) had findings consistent with spondyloarthritis (SpA) was highlighted as one of last year’s more actionable studies on SpA and axial SpA (axSpa) at the 2024 Rheumatology Winter Clinical Symposium (RWCS).

“There’s a lesson here,” said Eric M. Ruderman, MD, professor of medicine and associate chief of clinical affairs in the division of rheumatology at Northwestern University Feinberg School of Medicine, Chicago, Illinois. “We’ve spent a lot of time working with the dermatologists in the last 10 years to try to coordinate what we’re doing [for psoriatic disease]. It’s time to start working with the gastroenterologists more.”

The findings offer “more evidence” for an increasingly documented overlap of IBD with SpA — whether axial or peripheral — and suggest there is underdiagnosis of SpA among patients with IBD. “It’s important,” he said at the meeting, “because if there are meaningful joint symptoms, this should be considered when making treatment choices [for IBD],” just as rheumatologists must be aware of the potential for IBD in choosing therapies.

Dr. Ruderman also urged rheumatologists making treatment decisions for axSpA to more carefully consider the role of central pain in driving residual symptoms in patients on biologic disease-modifying antirheumatic drugs (bDMARDs). He pointed to a 2023 study of patients with radiographic axSpA (r-axSpA) receiving bDMARDs that showed significant associations between high central pain and a greater odds of having higher disease activity, independent of elevated C-reactive protein (CRP) levels.

“I’ve come to the conclusion that there’s a huge amount of central pain in our patients — that it [affects] 20%-30% of our patients, no matter what rheumatologic disease they have,” he said, “and if you don’t acknowledge and consider that, you’ll keep churning through medications that aren’t going to work because you’re not addressing a fundamental issue.”

Among other key studies of 2023 highlighted by Dr. Ruderman was a large retrospective cohort study showing a similar incidence of ankylosing spondylitis (AS) in US military men and women screened for chronic back pain and the GO-BACK withdrawal and retreatment trial of golimumab suggesting that dosing can be extended.

Meanwhile, last year brought more bad news for interleukin (IL)-23 inhibition in axSpA, with the termination of a phase 2 study of tildrakizumab (Ilumya). Good news came with the US Food and Drug Administration approval in 2023 of an intravenous formulation of the IL-17 inhibitor secukinumab (Cosentyx), which will be helpful for some Medicare patients. And moving forward, the biologic pipeline is SpA is “almost all about new pathways in the IL-17 arena,” Dr. Ruderman said.

Making Good Drug Choices for the Gut and the Joints

In the study of SpA among patients with IBD, reported at the EULAR 2023 meeting in Milan, Italy, rheumatologists assessed 110 consecutive patients — 34% of whom were diagnosed with Crohn’s disease and 59% of whom had ulcerative colitis — from a Danish IBD inception cohort. The patients, about 40% of whom were male, had a mean age of 42.

At the time of IBD diagnosis, 49% had arthralgias/musculoskeletal symptoms, 52% fulfilled Assessment of SpondyloArthritis International Society (ASAS) classification criteria for peripheral SpA, and 49% had synovitis and/or enthesitis verified by ultrasound, Dr. Ruderman said.

Gastroenterologists like the integrin antagonist vedolizumab (Entyvio) for some patients with IBD because “it’s a very gut-specific drug and doesn’t have as much impact on the systemic immune system as other drugs, but because it’s gut specific, it does nothing for peripheral or axial joint symptoms,” Dr. Ruderman said in an interview after the meeting. “We’ve seen patients switched to this drug from Humira [or other biologics] and suddenly they have joint pains they never had before.”

The IL-12/23 inhibitor ustekinumab (Stelara) and the IL-23 inhibitor risankizumab (Skyrizi) are also sometimes selected for IBD, but “neither work well for patients with confirmed axSpA or inflammatory axial spine pain and arthritis,” he said. “Maybe these patients belong on a TNF [tumor necrosis factor] inhibitor or a JAK [Janus kinase] inhibitor, which will manage both the joints and the gut.”

“It’s not that we don’t talk to one another, but as we get more and more drugs in this space — both us and the gastroenterologists — it behooves us to communicate better to make sure we’re making the right choices for patients,” Dr. Ruderman said in the interview.

On the flip side, there’s a clear link between patients with axSpA who have or later develop IBD, as was further documented in 2023 by a multicenter Spanish study that evaluated patients with SpA (including both radiographic and nonradiographic axSpA) for the prevalence of undiagnosed IBD, Dr. Ruderman said at the RWCS.

The study, reported at the American College of Rheumatology (ACR) 2023 annual meeting, included only patients who were bDAMRD-naive and off of steroids for at least 30 days. The researchers used elevated fecal calprotectin levels (≥ 80 mcg/g) followed by colonoscopy — and an endoscopic capsule study or MRI if colonoscopy was normal — to confirm a diagnosis of IBD. Of 559 patients, 4.4% had such a confirmed diagnosis (95% with Crohn’s disease), and interestingly, only 30% of these patients had clinical IBD symptoms.

“These are people who had no suspicion,” Dr. Ruderman said at the meeting. “You could say that maybe not having symptoms is not a big deal, but over time, maybe there will be consequences.”

The IL-17 inhibitors ixekizumab (Taltz), secukinumab, and bimekizumab (Bimzelx) are generally felt to be contraindicated in patients who have confirmed IBD, Dr. Ruderman noted in the interview. “While we don’t want to necessarily avoid those drugs, we need to be aware of the potential [for IBD],” he said, “and we need to have a low threshold of suspicion if our patients develop any GI symptoms.”

Considering Noninflammatory Residual Pain

The 2023 central pain study that caught Dr. Ruderman’s attention — research reported at the EULAR 2023 meeting — looked at 70 patients with r-axSpA receiving bDMARD treatment (mostly TNF inhibitors) who were being followed in an extension of the German Spondyloarthritis Inception Cohort. Investigators used the Widespread Pain Index (WPI) to help quantify central pain/central sensitization and the Ankylosing Spondylitis Disease Activity Score using C-reactive protein (ASDAS-CRP) to measure disease activity.

“Central pain was actually associated with having residual symptoms,” Dr. Ruderman said at the RWCS. Higher WPI scores were significantly associated with higher ASDAS-CRP scores, and a high WPI was also associated with higher odds of having high or very high disease activity (ASDAS > 2.1), independent of other factors including elevated CRP, the investigators reported in their abstract.

Arthur Kavanaugh, MD, professor of medicine at the University of California, San Diego, commented that “we don’t have great [non-opioid] treatments for pain,” prompting Dr. Ruderman to emphasize the importance of “resisting the urge to [automatically] switch to another biologic” without trying to discern whether residual pain is inflammatory or noninflammatory in nature.

“I’m really comfortable with this,” Dr. Ruderman said, noting that he prescribes drugs like duloxetine or pregabalin for suspected central pain. “For the statin (for cardiovascular disease prevention), I’m more likely to turn back to the primary care physician and work with them, but here it’s part of what we’re treating — it becomes part of our tool kits.”

The central pain issue, Dr. Ruderman said after the meeting, is one of recognition and nomenclature. In the last few years, “there’s been a tendency to get away from secondary fibromyalgia as a label. There’s a lot of baggage with the diagnosis, unfortunately,” he said in the interview. “And it’s all connected. … It’s very likely that the [central] pain signaling is triggered by the inflammatory pain in the first place.”

A New Look at Sex-Specific Incidence of AS

The study on AS in a retrospective cohort of 729,000 working-age US military service members “flew under the radar,” but its finding of a similar incidence in men and women who underwent screening for chronic back pain is “fascinating,” Dr. Ruderman said. Compared with females, men were not significantly more likely to have a diagnosis of AS (adjusted odds ratio [OR], 0.79; 95% CI, 0.61-1.02; P = .072), the researchers reported.

“We’ve always assumed that AS is a male disease, and that, as we got into nonradiographic axSpA, we would see more women. This study calls that into question,” he said.

More Light on bDMARD Dosage Extension and Withdrawal

The GO-BACK study of the TNF inhibitor golimumab (Simponi) randomized 188 patients with inactive nonradiographic axSpA after 6 months of 50 mg golimumab monthly to treatment withdrawal/monthly placebo, continued monthly treatment, or treatment every 2 months. The take-home message, Dr. Ruderman said, is that “withdrawal, but not reduction in dose, led to a higher risk of flare.”

Also notable in this study published in 2023 is that “almost 100% of those who flared were recaptured with the reinitiation of monthly dosing,” he said. “So you don’t lose if you try to stop … [although] I don’t think that will ever be a successful strategy.” (The proportion of patients without a disease flare over 12 months was 34% in the withdrawal group, 68% in the extended dosing group, and 84% in the continued monthly treatment group.)

Dosing extensions have been shown to be potentially viable with other biologics, “but with this one, it looks like you can spread it out almost with impunity because it doesn’t look like there’s much difference” between continuing monthly and extending, Dr. Kavanaugh commented.

Another study from 2023 of the IL-17A inhibitor ixekizumab in axSpA similarly showed a high recapture rate for patients who withdrew from therapy and then flared. In this phase 3 extension study in which 155 patients with inactive or low-level disease were randomized at week 24 to continued ixekizumab or placebo, 53% of placebo patients flared by 2 years, compared with 13% in the ixekizumab arm. Of those who flared, 96% recaptured low disease activity with re-initiation of therapy.

“It’s the same story. You might get away with [stopping the therapy] because it’s not 100% who flared. But is it worth it?” Dr. Ruderman said.

IL-23 Inhibition in Axial Disease and the Pipeline

Is the chapter on IL-23 inhibitors closed for axSpA? Aside from a possible role for axial disease in psoriatic arthritis (PsA), it likely is, Dr. Ruderman said, pointing to the phase 2 randomized, double-blind, placebo-controlled study of tildrakizumab in patients with AS that was terminated at week 24 after the drug showed no difference in efficacy from placebo.

Dr. Kavanaugh agreed. “This adds to the data on risankizumab and ustekinumab in studies done properly in AS,” he said. “There’s no benefit.”

The “real issue” still to be determined, said Dr. Ruderman, “is what is the role of IL-23 inhibitors in patients with axial PsA?”

A post-hoc analysis of data from the SELECT PsA 1 and 2 trials, published in 2023, showed greater improvement in the overall Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score in patients with axial disease who received 15 mg upadacitinib (Rinvoq), compared with placebo.

“It suggests there’s improvement in the patients with axial PsA as defined [by a high BASDAI score], but they didn’t compare this with patients without axial disease … it’s muddy,” Dr. Ruderman said. Other research that’s underway should provide clarity, Dr. Kavanaugh said.

The pipeline for new treatments for SpA, including axSpA, is focused on new biologics targeting the IL-17 pathways, as well as a fair number of targeted synthetics, Dr. Ruderman said. “What will be interesting to me is what happens with the TYK2 inhibitors … because one of the postulated mechanisms is that the IL-23 signals through TYK-2,” he said. “So if that’s the mechanism, will they really help our patients with axial disease? We need the trials to find out.”

The intravenous formulation of secukinumab, approved in 2023 for AS, nr-axSpA, and PsA, is a “nice addition to our armamentarium, Dr. Ruderman noted in his 2023 review. “For years, a patient doing well on an IL-17 inhibitor for their axial disease or their psoriatic disease would hit Medicare age and suddenly couldn’t afford subcutaneous administration, and we had to switch them over to an IV-TNF inhibitor,” he said. “Now we have an IV IL-17 inhibitor.”

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

Tools to screen for spondyloarthritis (SpA) among people with the extra-musculoskeletal conditions that commonly co-occur with SpA — psoriasis, uveitis, and inflammatory bowel disease (IBD) — show potential for their use in target populations but have limited generalizability for patients at risk for SpA, according to findings from a scoping review of 18 tools.

Prior to the review comparing available tools, first author Vartika Kesarwani, MBBS, of the University of Connecticut, Farmington, and colleagues wrote that the performance of SpA screening tools in dermatology, ophthalmology, and gastroenterology contexts had not been evaluated.

“Given the evolving landscape of therapeutics for spondyloarthritis, recognizing the full spectrum of disease manifestations in individual patients becomes increasingly important. This knowledge can inform treatment decisions, potentially altering the course of the disease,” corresponding author Joerg Ermann, MD, of Brigham and Women’s Hospital, Boston, said in an interview.

In the study, published on February 1 in Arthritis Care & Research, the investigators identified 13 SpA screening tools for psoriasis (screening specifically for psoriatic arthritis), two for uveitis, and three for IBD. All tools with the exception of one for uveitis were patient-oriented questionnaires with an average completion time of less than 5 minutes.

Overall, the researchers found significant variability in the nature of the questions used to identify clinical features of SpA; 15 tools included at least one question on back pain or stiffness; 16 tools had at least one question on joint pain, swelling, or inflammation; 10 included questions about heel or elbow pain; and 10 included questions about swelling of digits.

All 13 of the psoriasis tools were screened for peripheral arthritis, while 10 screened for axial involvement, eight screened for enthesitis, and eight screened for dactylitis.

All three of the IBD tools were screened for axial involvement and peripheral arthritis, and two were screened for enthesitis and dactylitis.

Both of the uveitis tools were screened for axial involvement, but neither was screened for peripheral arthritis, enthesitis, or dactylitis.

Sensitivities in the primary validation groups were similar for the 16 tools for which sensitivities were reported, ranging mainly from 82% to 92% for 11 psoriasis tools, 91% to 96% for uveitis tools, and 83% to 93% for IBD tools.

Specificities for psoriasis tools ranged from 69% to 83% for all but two of the tools, which was 46% for one and 35%-89% for another across three geographical cohorts. For uveitis tools, specificities were 91%-97% for uveitis tools, and for IBD tools, 77%-90%. Most of the secondary validations involved psoriasis tools, and these were generally lower and also more variable.
 

The Case for a Generic Tool

The relatively few SpA tools for patients with uveitis and IBD, compared with psoriasis, may be attributable to a lack of awareness of the association between these conditions on the part of ophthalmologists and gastroenterologists, the researchers wrote in their discussion. Therefore, a generic SpA screening tool that could apply to any extra-articular manifestation might increase screening across clinical settings and streamline rheumatology referrals, they noted.

The review’s findings were limited by several factors, including the inclusion of only articles in English and the relatively few tools for uveitis and IBD patients, the researchers noted.

The findings suggested that although the performances of the tools are similar, their degree of variability supports the value of a generic tool, they concluded.
 

Streamlining to Increase Screening

“Compared to the large amount of research in psoriasis and psoriatic arthritis, relatively little has been done with regard to screening for spondyloarthritis in patients with uveitis or IBD,” Dr. Ermann told this news organization. “Despite the numerous screening tools developed for psoriatic arthritis, no ideal screening tool has emerged, and the implementation of effective screening strategies in clinical practice is challenging,” he said. In the current study, the compartmentalization of research into individual conditions like psoriasis, uveitis, and IBD was notable despite the interconnected nature of these conditions with SpA, he added.

In practice, Dr. Ermann advised clinicians to maintain a high index of suspicion for SpA in patients presenting with psoriasis, uveitis, or IBD and proactively ask patients about symptoms outside their primary specialty.

“Future research should focus on developing a universal spondyloarthritis screening tool that is comprehensive, easily understandable, and can be used across various clinical settings,” he said.
 

Need for Early Identification and Closer Collaboration

A delay in SpA diagnosis of as little as 6 months can lead to worse outcomes, Rebecca Haberman, MD, a rheumatologist at NYU Langone Health, New York City, said in an interview. “Patients with these conditions may first present to dermatologists, gastroenterologists, and/or ophthalmologists before rheumatologic evaluation. If we can identify these patients early at this stage, we might be able to improve outcomes, but the question remains of how we get these patients to the proper care,” she said.

The review examined the currently available screening tools for use in patients with psoriasis, IBD, and uveitis and highlights the heterogeneity of these tools in terms of use and disease characteristics, as well as the lack of tools for use in gastroenterology and ophthalmology offices, Dr. Haberman said.

The review “proposes several important ideas, such as creating a unified screening tool that can be used across diseases and fields, to reduce confusion by providers and help provide standardization of the referral process to rheumatologists,” she said.

“Even though SpA is prevalent in many patients with psoriasis, IBD, and uveitis, it remains very underdiagnosed, and often referrals to rheumatologists are not made,” Dr. Haberman told this news organization. Diagnostic challenges likely include SpA’s heterogeneous presentation, the specialists’ lack of knowledge regarding the connection between these conditions and joint disease, and time pressures in clinical settings, she said.

“Other practitioners are not always trained to ask about joint pain and often have limited time in their exams to ask additional questions. To overcome this, more collaboration is needed between dermatologists, gastroenterologists, ophthalmologists, and rheumatologists, as many of our diseases live in the same family,” Dr. Haberman said.

Improving clinician education and creating relationships can help facilitate questions and referrals, she said. Short, effective screening tools that can be filled out by the patient may also help overcome specialists’ discomfort about asking musculoskeletal-related questions and would save time in the clinical visit, she said.

More research is needed to identify the best screening tools and questions and which are the most highly sensitive and specific, Dr. Haberman said. “This will allow for rheumatologists to see patients who may have SpA earlier in their course without overwhelming the system with new referrals.” In addition, more work is needed on how and whether screening tools are being used in clinical practice, not just in research studies, she said.

The study was supported by a grant from the National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases. The researchers and Dr. Haberman had no financial conflicts to disclose.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

The US Food and Drug Administration has approved the first interchangeable, high-concentration, citrate-free adalimumab biosimilar, adalimumab-ryvk (Simlandi).

This is the 10th adalimumab biosimilar approved by the regulatory agency and the first biosimilar approval in the US market for the Icelandic pharmaceutical company Alvotech in partnership with Teva Pharmaceuticals.

“An interchangeable citrate-free, high-concentration biosimilar adalimumab has the potential to change the market dynamics in a rapidly evolving environment for biosimilars in the U.S.,” said Robert Wessman, chairman and CEO of Alvotech, in a company press release on February 23.

Adalimumab-ryvk was approved in the European Union in 2021 and in Australia and Canada in 2022. 

Adalimumab-ryvk is indicated for adults with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, Crohn’s disease, plaque psoriasis, hidradenitis suppurativa, and noninfectious intermediate and posterior uveitis and panuveitis. In pediatric patients, it is indicated for polyarticular juvenile idiopathic arthritis in children 2 years of age and older and Crohn’s disease in children 6 years of age and older.

Adalimumab-ryvk is the third Humira biosimilar overall granted interchangeability status, which allows pharmacists (depending on state law) to substitute the biosimilar for the reference product without involving the prescribing clinician. Adalimumab-adbm (Cyltezo), manufactured by Boehringer Ingelheim, and adalimumab-afzb (Abrilada), manufactured by Pfizer, were previously granted interchangeability status; however, they both are interchangeable with the low-concentration formulation of Humira, which make up only an estimated 15% of Humira prescriptions, according to a report by Goodroot. 

Adalimumab-ryvk will be launched “imminently” in the United States, according to the press release, but no specific dates were provided. It is also not yet known how the biosimilar will be priced compared with Humira. Other adalimumab biosimilars have launched with discounts from 5% to 85% of Humira’s list price.

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Pooled data from 9225 adults with psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) showed no new safety signals with extended exposure to ixekizumab (Taltz).

METHODOLOGY:

• Researchers combined patient data from 25 randomized, controlled trials of the safety and effectiveness of at least one dose of ixekizumab in adults with PsO (n = 6892), PsA (n = 1401), and axSpA (n = 932).
• The study population included patients with a mean age of approximately 43-49 years; at least 49% were male and at least 74% were White across the three conditions.
• Patients’ median duration of ixekizumab exposure was 1.3 years for PsO, 1.4 years for PsA, and 2.7 years for axSpA, with data up to 6 years for PsO and up to 3 years for PsA and axSpA.
• The primary outcomes were exposure-adjusted incidence rates per 100 patient-years overall and at successive year intervals for treatment-emergent adverse events, serious adverse events, and selected adverse events of interest.

TAKEAWAY:

• The incidence rate per 100 person-years for any treatment-emergent adverse event was 32.5 for PsO, 50.3 for PsA, and 38.0 for axSpA; these did not increase with lengthier exposure.
• The incidence rates for serious adverse events for patients with PsO, PsA, or axSpA were 5.4, 6.0, and 4.8 per 100 person-years, respectively.
• A total of 45 deaths were reported across the studies, including 36 in patients with PsO, six with PsA, and three with axSpA.
• Infections were the most common treatment-emergent adverse events across all patient groups, reported in patients at rates of 62.5% with PsO, 52.4% with PsA, and 57.9% with axSpA; incidence of infections did not increase over time.

IN PRACTICE:

“These final, end-of-study program results surrounding the long-term use of [ixekizumab] in patients with PsO, PsA, and axSpA should serve as an important point of reference for physicians considering [ixekizumab],” the researchers wrote.

SOURCE:

The lead author on the study was Atul Deodhar, MD, of Oregon Health & Science University, Portland. The study was published online on February 12 in Arthritis Research & Therapy.

LIMITATIONS:

Study limitations included the small sample sizes and short treatment durations in some studies, the primarily White study population, the inability to stratify risk, the lack of a long-term comparator, and potential survivor bias.

DISCLOSURES:

The studies in the review were supported by Eli Lilly. Lead author Dr. Deodhar disclosed an honorarium and serving on advisory boards at AbbVie, Bristol-Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, as well as research grants from AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, MoonLake, Novartis, Pfizer, and UCB.
 

A version of this article appeared on Medscape.com.

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

Comorbidities may play a large role in driving poor pregnancy outcomes in pregnant people with certain immune-mediated inflammatory diseases (IMIDs).

In a new study of 12 individual IMIDs, people with rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) did not have signficantly increased risk for preterm birth (PTB) or low birth weight (LBW), compared with people who did not have an IMID, after adjusting for additional chronic conditions and other confounding factors.

The study was published online on February 1 in eClinicalMedicine.

While many studies have explored the relationships between pregnancy outcomes and IMIDs, “the impact of comorbidities on the relation between IMIDs and pregnancy course is insufficiently examined,” the authors wrote. These previous studies also tended to have a small sample size.
 

Pregnancy Outcome Risks Varied Between IMIDs

To remedy this, researchers used electronic health record data from Providence St Joseph Health — a multistate integrated healthcare system — to identify more than 365,000 pregnant people with live births between January 1, 2013, and December 31, 2022. The cohort included more than 5700 people with at least one of 12 IMIDs: Psoriasis, IBD, RA, spondyloarthritis (SpA), multiple sclerosis, systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), antiphospholipid syndrome (APS), Sjögren syndrome (SjS), vasculitis, sarcoidosis, and systemic sclerosis. The study included only live births with a gestational age of 20 weeks or greater.

Researchers compared maternal-fetal health outcomes between the two groups, controlling for comorbidities including diabetes, cardiovascular disease, chronic kidney disease, obesity, and depression. They also accounted for confounding variables including race, age, smoking status, and socioeconomic status.

In total, 83% of people in the IMID group had no immunomodulatory medication prescriptions during their pregnancy. Of the 17% taking medication, 48%-70% continued taking their medication until delivery. Most patients were White, comprising 62.9% of the non-IMID group and 73.1% of the IMID group.

After adjusting for comorbidities, patients with any of the 12 IMIDs had a 10%-20% higher risk for PTB, LBW, small for gestation age (SGA), and cesarean section than did comparators.

But these risks varied between IMIDs. Patients with RA and IBD did not have an increased risk for PTB or LBW. However, when researchers did not control for comorbidities, pregnancy risks were higher and showed statistical significance in these two groups.

“This suggests that for RA and IBD, comorbidities may be a more important factor for adverse outcomes than the underlying autoimmune disease,” senior author Jennifer Hadlock, MD, an associate professor and director of medical data science at the Institute for Systems Biology in Seattle, Washington, said in a video accompanying a press release.

Overall, the analysis found that women with IMIDs were approximately two to three times more likely to have chronic comorbidities than the control group.

Like previous studies, there was a strong association between SLE and APS and poor pregnancy outcomes, even after controlling for confounding factors. Patients with SpA had a 50% increased risk for PTB, while those with SLE and APS had more than a twofold higher risk. Patients with SLE were 90% more likely than comparators to deliver babies with an SGA condition, while RA patients had a 30% higher risk. SLE was the only condition with an increased risk for LBW (relative risk, 3.5). IBD, RA, PsA, SpA, SLE, APS, and SjS were all associated with a higher likelihood of delivery via cesarean section.

“The findings of this study reveal that the associations between IMIDs and adverse pregnancy outcomes are influenced by the specific type of IMIDs and the presence of comorbidities,” the authors wrote.
 

A Large Study, But How Representative Is It?

Asked to comment on the study, Catherine Sims, MD, a rheumatologist at Duke University Medical Center in Durham, North Carolina, noted that the analysis was much larger than many reproductive rheumatology studies, and “their statistics were phenomenal.”

She agreed that “not all autoimmune diseases are created equal when it comes to pregnancy-associated risks.” However, she added that this study’s patient population may not be totally representative of pregnant people with IMIDs or autoimmune diseases.

“We’re making generalizations about autoimmune diseases based on this demographic of White women who are not taking immunosuppression,” she said.

“We know that race and ethnicity play a huge role in pregnancy outcomes, and Black women have higher maternal and fetal morbidity and mortality, which is likely related to systemic racism and biases in the medical system,” she added. “While the study did control for sociodemographic factors, the population studied is not diverse.”

Only 17% of people with IMID in the cohort were on immunosuppressive medication, which could suggest low disease activity in the study population, Dr. Sims said. If the population generally had well-controlled disease, that could have positioned them for better pregnancy outcomes.

The authors noted that their analysis did not have information on IMID disease activity or severity — one of the limitations of the study.

However, the authors argued that the observed low prescription rate during the study may have increased poor pregnancy outcomes.

“Although this reflects real-world care in the population studied, results from this study may show higher risk than might be achieved with recommended care guidelines,” they wrote.

Ultimately, the authors argued that these findings show how co-occurring health conditions can affect pregnancy outcomes in autoimmune diseases, particularly for RA and IBD.

“There is a need to take comorbidities into consideration for guidelines for patients with inflammatory bowel disease and rheumatoid arthritis and when designing future research to investigate maternal health in patients with IMIDs,” they wrote.

The study was funded by the National Institutes of Health. Dr. Sims declared no relevant financial relationships. Dr. Hadlock has received research funding (paid to the institute) from Pfizer, Novartis, Janssen, Bristol-Myers Squibb, and Gilead.

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

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Adults with axial spondyloarthritis (axSpA) with longstanding back pain symptoms had response rates to nonsteroidal anti-inflammatory drugs (NSAIDs) that were no different from patients with non-axSpA back pain of similar duration, according to findings from a prospective study.

METHODOLOGY:

The researchers recruited 233 consecutive outpatients with chronic back pain, including 68 with axSpA and 165 with non-axSpA back pain.

The mean ages of the participants in the axSpA and non-axSpA groups were 42.7 years and 49.3 years, respectively; symptom durations were approximately 15 years in both groups.

Participants were given NSAIDs and “any response” was defined as back pain improvement of more than two units on the Numerical Rating Scale, while “good response” was defined as an improvement of > 50% compared with baseline.

TAKEAWAY: 

After 4 weeks, 30.9% of patients with axSpA and 29.1% of patients with non-axSpA back pain had any response, and 23.5% and 16.4% of patients with axSpA and non-axSpA back pain, respectively, had a good response.

The proportion of patients showing improvement ranged from 19% to 31% in both groups after 4 weeks of treatment.

No significant differences in response appeared in subgroups of patients based on inflammatory back pain stage or in different axSpA stages.

IN PRACTICE:

“We think that this information has an effect on clinical practice since a response to NSAIDs is an important criterion in the ASAS [Assessment of SpondyloArthritis international Society]/European Alliance of Associations for Rheumatology treatment recommendations that may influence decisions to initiate treatment with biologic or targeted-synthetic DMARDs [disease-modifying antirheumatic drugs]. Further, a good response to NSAIDs is also an important clinical feature in the ASAS classification criteria,” the researchers wrote.

SOURCE: 

The lead author on the study was Xenofon Baraliakos, MD, of Ruhr University Bochum, Germany. The study was published online on January 15, 2024, in The Journal of Rheumatology.

LIMITATIONS:

The uneven sex match in the diagnoses and the history of NSAID treatment among patients in both groups were potential limiting factors. The researchers also noted that a similarly conducted study in patients with early disease could have findings that are “much different.”

DISCLOSURES:

The study was sponsored in part by Novartis. The researchers reported no relevant financial relationships. 
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

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

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

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

TOPLINE: 

Men with an inflammatory arthritis (IA) diagnosis are less likely to be childless than healthy comparators, according to an epidemiological study.

METHODS:

• 10,865 men in the Norwegian Arthritis Registry were compared with 54,325 men without IA, matched by age and location.
• In the arthritis group, 37% had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis.
• Researchers used childlessness and number of children as proxies for male fertility.

TAKEAWAY:

• 21% of men with IA were childless compared with 27% in the healthy cohort (P < .001).
• On an average, a man with IA had 1.80 children whereas a man in the control group had 1.69 children (P < .001).
• These findings were consistent over time, but the most pronounced difference between groups was seen in men diagnosed after the year 2000.

IN PRACTICE:

The finding “is novel and generates new hypotheses regarding associations between fertility, inflammatory rheumatic diseases, and immune-modulating drugs,” the authors wrote.

SOURCE:

First author Gudrun David Sigmo, of the department of rheumatology at Stavanger (Norway) University Hospital, and colleagues had their work published online on January 23, 2024, in Annals of the Rheumatic Diseases.

LIMITATIONS:

The analysis relied on administrative data, and researchers did not have data on confounding factors.

DISCLOSURES:

The study was funded by the nonprofit organizations Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and Fagsenter for medisins-ke kvalitetsregistre i Helse Vest. The authors declared no relevant conflicts of interest.

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

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

A new diagnostic tool can effectively discriminate different rheumatologic conditions and could potentially aid in the diagnosis of early inflammatory arthritis.

The algorithm — called Genetic Probability tool (G-PROB) — uses genetic information to calculate the probability of certain diseases.

University of Manchester

“At such an early stage of disease, it’s not always easy to determine what the final outcome will be with respect to final diagnosis,” said John Bowes, PhD, a senior lecturer in the division of musculoskeletal & dermatological sciences at the University of Manchester in the United Kingdom. He was a senior author of the newest study of G-PROB. “What we are hoping for here is that genetics can help [clinicians] with the decision-making process and hopefully accelerate the correct diagnosis and get individuals onto the correct treatment as early as possible.”
 

Creating the Algorithm

G-PROB was first developed by an international group of scientists with the goal of using genetic risk scores to predict the probabilities of common diagnoses for patients with early signs of arthritis, such as synovitis and joint swelling. According to the study authors, about 80% of these types of patients are eventually diagnosed with the following conditions: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), psoriatic arthritis (PsA), ankylosing spondylitis (AS), and gout.

The algorithm combines existing knowledge about single-nucleotide polymorphisms from prior genomic studies to create genetic risk scores — also called polygenic risk score (PRS) — for multiple diseases. Using these scores, the program then calculates the probabilities of certain diagnoses for a patient, based on the assumption that at least one disease was present.

In this first study, researchers trained the tool on simulated data and then tested it in three patient cohorts totaling about 1700 individuals from the Electronic Medical Records and Genomics database and Mass General Brigham Biobank. In the initial study, G-PROB identified a likely diagnosis in 45% of patients, with a positive predictive value (PPV) of 64%. Adding these genetic scores to clinical data improved diagnostic accuracy from 39% to 51%.
 

Validating G-PROB

But data from these biobanks may not necessarily be representative of early arthritis in patients appearing in outpatient clinics, noted Dr. Bowes. In this new study, researchers sought to independently validate the original study’s findings using data from the Norfolk Arthritis Register, a community-based, long-term observational study on inflammatory polyarthritis. The team applied G-PROB in this cohort and then compared the tool’s probabilities for common rheumatic conditions to the final clinician diagnosis.

The study ultimately included 1047 individuals with early inflammatory arthritis with genotype data. In the cohort, more than 70% (756 individuals) were diagnosed with RA. Of the remaining patients, 104 had PsA, 18 had SLE, 16 had AS, and 12 had gout. The research team also added an “other diseases” category to the algorithm. A total of 141 patients fell into this category and were diagnosed with diseases including chronic pain syndrome (52 individuals), polymyalgia rheumatica (29 individuals), and Sjögren’s syndrome (9 individuals).

G-PROB was best at excluding diagnoses: Probabilities under 5% for a single disease corresponded to a negative predictive value (NPV) of 96%. If probabilities for two diseases were both < 5%, the NPV was 94%.

For patients with a single probability above 50%, the tool had a PPV of 70.3%. In 55.7% of all patients, the disease with the highest probability ended up being the final diagnosis.

Generally, PRSs, as well as tests using biomarkers, were better at excluding diagnoses than affirming them, noted Matthew Brown, MBBS, MD, a professor of medicine at King’s College London, who was not involved with the research. If disease prevalence is low, then a test aimed at diagnosis of that disease would be better at excluding a diagnosis than affirming it, he explained.

Queensland University of Technology

Can G-PROB Improve Diagnosis?

The new study’s key contribution was that it independently validated findings from a previous study, noted Katherine Liao, MD, a rheumatologist at Brigham and Women’s Hospital in Boston, Massachusetts. She coauthored an accompanying editorial to the newest study and coauthored the original G-PROB paper.

Dr. Liao

This new study also brought up an important question about G-PROB that has yet to be tested: Will this tool help clinicians make more efficient and accurate diagnoses in practice?

A prospective trial would be necessary to begin answering this question, both Dr. Bowes and Dr. Liao agreed. For example, one clinician group would have access to G-PROB data, while another would not, and “see if that helps [the first group] make the diagnosis faster or more accurately,” Dr. Liao said.

Dr. Bowes was also interested in exploring if combining G-PROB with other clinical data would improve diagnostic performance.

“Genetics isn’t the full story,” he said. Dr. Bowes saw genetics as one additional, complementary tool in a clinician’s toolbox.

Future studies were needed to understand the clinical utility of genetic information in conjunction with current diagnostic practices, such as imaging, physical exams, and lab results, Dr. Liao and her editorial coauthors argued. 

“For example, in cardiovascular disease, the clinical utility of polygenic risk scores has been defined by their ability to improve risk stratification beyond what is already achieved with more common risk factors and measures such as cholesterol levels, smoking status, and coronary calcium scores,” Dr. Liao and her coauthors wrote. “Similarly, a polygenic risk score for breast cancer would not be clinically implemented alone for risk prediction but rather as one risk factor among others, such as hormonal and reproductive factors and prior mammographic data.”
 

Future of Genetics in Rheumatology

An additional hurdle for using tools like G-PROB was that a patient must have undergone DNA sequencing, and these data must be available to clinicians. Even a decade ago, this type of testing may have seemed unrealistic to incorporate in daily practice, Dr. Liao noted, but technological advancements continue to make genetic sequencing more accessible to the public.

There are already efforts in the United Kingdom to incorporate genetics into healthcare, including trials for PRSs and heart disease, noted Dr. Bowes, as well as large-scale studies such as Our Future Health.

“As these population-based studies expand more, a high proportion of individuals should hopefully have access to this kind of data,” he said.

Brown added that genetic testing is already used to make rheumatology diagnoses.

“[HLA] B-27 testing, for example, is an extremely commonly used test to assist in the diagnosis of ankylosing spondylitis. Is it that different to change to a PRS as opposed to a straight HLA testing? I don’t think it is,” he said.

While there would need to be systematic training for clinicians to understand how to calculate and use PRSs in daily practice, Dr. Brown did not think this adjustment would be too difficult.

“There is a lot of exceptionalism about genetics, which is actually inappropriate,” he said. “This is actually just a quantitative score that should be easy for people to interpret.”

Dr. Bowes and Dr. Brown reported no relevant financial relationships. Dr. Liao worked as a consultant for UCB.

A version of this article appeared on Medscape.com.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.

SAN DIEGO – Monthly use of intravenously administered secukinumab (Cosentyx) proved its efficacy over placebo in treating psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) in two industry-sponsored, randomized, double-blinded, phase 3 trials of the drug’s second and newly approved route of administration.

The studies of the human monoclonal antibody secukinumab, an interleukin-17 inhibitor, were presented at the annual meeting of the American College of Rheumatology. A subcutaneously injectable formulation of the drug is available, and the Food and Drug Administration approved the IV form for the conditions in October, although at a recommended lower monthly dose than the new trials examined.

In the PsA trial, 191 patients took IV secukinumab, and 190 took placebo. For the primary endpoint, the percentages who reached at least a 50% improvement in American College of Rheumatology response criteria (ACR 50) at 16 weeks were 31.4% and 6.3%, respectively (P < .0001).

In the axSpA trial, 264 patients took IV secukinumab, and 262 took placebo. The primary endpoint, at least a 40% improvement in Assessment of the Spondyloarthritis International Society response criteria (ASAS 40), was met at 16 weeks by 40.9% and 22.9%, respectively (P < .0001).

“Both studies appear to present clear efficacy of IV route administration of secukinumab with no clear increase in safety signals,” consultant rheumatologist Nicola Goodson, MBChB, PhD, of Aintree University Hospital in Liverpool, England, said in an interview.

“Offering IV administration as an option to patients is helpful,” added Dr. Goodson, who was not involved with the study but is familiar with its findings.

As Dr. Goodson explained, secukinumab “was the first IL [interleukin]-17 inhibitor used to treat spondyloarthropathies, and we have been using subcutaneous secukinumab to treat psoriasis, psoriatic arthritis, and axial spondyloarthritis/ankylosing spondylitis since 2016 in the U.K. Our experience with this medication has been good with similar efficacy to anti-TNF [tumor necrosis factor] therapy in axial spondyloarthritis. The medication is generally well-tolerated, and the subcutaneous pen injection device is easy for patients to use.”

However, IV treatment may speed up onset of action, she said, and it may be useful in situations when compliance is a challenge.
 

PsA trial details

In the PsA trial, known as INVIGORATE-2, researchers recruited patients who met the CASPAR criteria for active PsA with symptoms for ≥ 6 months, and had ≥ 3 tender joints out of 78 joints and ≥ 3 swollen joints out of 76.

Participants with a mean age of 48, including 55% females, were randomized 1:1 to receive placebo or secukinumab (6 mg/kg at baseline followed by 3 mg/kg every 4 weeks). Those in the placebo group were switched to the same monthly doses of secukinumab at 16 weeks.

“Patients who switched from the placebo had a similar increase of efficacy as the original treated group,” rheumatologist Alan J. Kivitz, MD, of the Altoona Center for Clinical Research, in Duncansville, Penn., said in his presentation at the meeting. Specifically, at 52 weeks, the groups had similar ACR 50 response rates: 58% with secukinumab and 64% with placebo-to-secukinumab.

The fact that patients in the original placebo group who received 3 mg IV doses without 6-mg loading doses achieved ACR response rates similar to those who took secukinumab during the whole trial “could suggest that the IV loading dose may not be required. This would need to be explored in a randomized head-to-head study, but it’s an interesting observation that may reduce costs and exposure to higher doses of medication at the start of treatment,” Dr. Goodson said.

Among the patients who received secukinumab at any point in the study, 63% had a treatment-emergent adverse event, including 5.9% with serious events. One death was reported in the placebo group before week 16. No other deaths were reported.
 

AxSpA trial details

In the axSpA trial, called INVIGORATE-1, researchers recruited people aged ≥18 years with a diagnosis of active radiographic axSpA according to modified New York criteria or nonradiographic axSpA according to ASAS criteria, and all had inflammatory back pain for ≥6 months with an onset before age 45. They were randomized at a 1:1 ratio to receive IV secukinumab (6 mg/kg loading dose, followed by 3 mg/kg every 4 weeks) or placebo for 16 weeks. At that point, the placebo group switched to the same monthly doses of IV secukinumab.

Participants had a mean age of about 39, and about one-third were female.

Following the statistical superiority in ASAS 40 response rates seen with IV secukinumab at week 16, patients who from there switched from placebo to IV secukinumab achieved comparable ASAS 40 response rates to those of patients originally randomized to secukinumab by week 24, reaching 66.8% for those on secukinumab the whole time and 74.9% for those who switched.

Secondary outcome measures were similar in both groups at week 52.

Among all patients who took secukinumab – the percentage with any adverse event was 63.2%, and 6% had a nonfatal adverse event deemed serious. There was one death during secukinumab treatment not suspected to be related to treatment.

In a presentation about the axSpA study findings, Atul Deodhar, MD, of Oregon Health & Science University, noted that “having an IV biologic available in the U.S. has some advantages. There are certain insurance providers such as Medicare where it is more economical for the patient to have an IV drug available.”

Dr. Deodhar also noted that in October the FDA approved a recommended lower dose for the IV treatment than in the study: 1.75 mg/kg instead of 3 mg/kg following the loading dose. That’s because the 3 mg/kg dose caused blood levels to be higher than those in the subcutaneous form, he said.

The FDA made the same dose recommendation for PsA.
 

Study limitations

Dr. Goodson, the U.K. consultant rheumatologist, noted a limitation of the trials: “It would have been interesting to compare IV to subcutaneous route secukinumab.” Still, the findings suggest that “the safety and efficacy of IV administration appears comparable,” she said.

“IV administration will have associated costs of attending hospital or infusion clinics,” she added, “and the cost of additional staff and administration need to be considered.”

Novartis, the maker of secukinumab, funded both studies. The PsA study authors report multiple relationships with industry, and some, such as Dr. Kivitz, have connections to Novartis. The axSpA study authors also report multiple relationships with industry, and some, such as Dr. Deodhar, have connections to Novartis. Some authors of both studies are Novartis employees. Dr. Goodson disclosed financial relationships with UCB and AbbVie.