February 03, 2020
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Updated EULAR recommendations for RA allow larger role for JAK inhibitors

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Josef S. Smolen, MD
Josef S. Smolen

When treating rheumatoid arthritis initially with methotrexate and glucocorticoids, the presence of poor prognostic factors should prompt physicians to add any JAK inhibitor or biologic DMARD, with no preference given to the latter, according to a 2019 update to the EULAR recommendations for RA management.

“Over the course of the decade, the development of new classification criteria for RA; novel information on optimal clinical targets, such as the American College of Rheumatology (ACR)-EULAR remission definitions; evolution of treatment algorithms and strategies and the advent of new drugs already necessitated two updates of the EULAR recommendations,” Josef S. Smolen, MD, of the Medical University of Vienna, and colleagues wrote in the Annals of the Rheumatic Diseases.

“Although relevant data accrue rapidly, several of the recommendations, even in the 2016 update, were based on rather low levels of evidence and many have elicited intense debates because of variable interpretations of evidence and empirical approaches,” they added. “Three years have passed since the last update.”

In the face of several developments — including newly licensed drugs, the long-term efficacy and safety of long-approved agents, comparative effectiveness studies, therapeutic targets and treatment strategies, and safety aspects — the EULAR executive committee approved the effort to update the recommendations.

Image of arthritic hand 
Then treating RA initially with methotrexate and glucocorticoids, the presence of poor prognostic factors should prompt physicians to add any JAK inhibitor or biologic DMARD, with no preference given to the latter, according to a 2019 update to the EULAR recommendations.
Source: Adobe

The steering committee — made up of eight rheumatologists, one patient representative and two fellows — performed two systematic literature reviews. The reviews focused on the efficacy of DMARDs, glucocorticoids, treatment strategies and safety, as well as data from randomized control trials and extensions. Literature reviewed in the development of the 2016 update were used as a starting point.

A 47-member task force — including members of the steering committee, three patients, two health professionals and two delegates of the EULAR young rheumatologists network — considered the new evidence. The members used a predefined voting process to amend, or leave unchanged, items in the 2016 recommendations, as well as assigning strengths and levels of agreement.

The task force ultimately developed five overarching principles and 12 recommendations. The members recommended initial treatment with methotrexate plus glucocorticoids, with stratification according to risk factors if the response is insufficient withing 3 to 6 months. If the patient presents poor prognostic factors — such as the presence of autoantibodies, high disease activity, early erosions or the failure of two conventional synthetic DMARDs — any JAK inhibitor or biologic DMARD should be added.

This is in contrast to the 2016 recommendations, which stated “If the treatment target is not achieved with the first [conventional synthetic] DMARD strategy when poor prognostic factors are present, addition of a [biologic] DMARD or a [targeted synthetic] DMARD should be considered; current practice would be to start a [biologic] DMARD.” According to the task force, the preference for biologic DMARDs was eliminated due to new evidence regarding the successful long-term efficacy and safety of JAK inhibitors. In addition, “should be considered” was changed to “should be added.”

Furthermore, if that fails, any other biologic DMARD, from the same or another class, or targeted synthetic DMARD is recommended. DMARDs may be tapered, but not ceased, upon sustained remission.

“Adhering to these recommendations, which are based on systematic literature reviews and opinions of experts from around the world, will allow optimal treatment of patients with RA at the beginning of the third decade of this century,” Smolen and colleagues wrote. “Using the many therapeutic options available, the treatment target can be reached in most patients; however, about 20% to 30% remain refractory to current therapies.”

“For these, new treatment options, but also better insights into the pathogenesis of RA will be needed,” they added. “The research agenda points to unresolved questions and enables future task forces to further improve the EULAR recommendations.” – by Jason Laday

Disclosure: Smolen reports grants from Abbvie, AstraZeneca, Janssen, Eli Lilly, Novartis and Roche, as well as honoraria from Abbvie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO, Janssen, Eli Lilly, MSD, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi and UCB. Please see the study for all other authors’ relevant financial disclosures.