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What Will Be the Place of JAK Inhibitors in the New ACR 2020 Pharmacologic Recommendations for the Management of RA?

Released: December 23, 2020

Expiration: December 22, 2021

Stanley B. Cohen
Stanley B. Cohen, MD
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The new American College of Rheumatology (ACR) 2020 pharmacologic recommendations for the management of rheumatoid arthritis (RA) were presented at this year’s ACR/ARP Convergence meeting, and we expect publication in early 2021.

One of the interesting facets of the proposed recommendations was the placement of JAK inhibitors. In the 2015 recommendations, biologics were recommended prior to JAK inhibitors, but that was because much fewer data were available.

In the last 4 or 5 years there have been numerous clinical trial data presented on JAK inhibitors; baricitinib has been approved, upadacitinib has been approved, and filgotinib has been approved in Europe. Based on those trial data, the committee conditionally recommended that after conventional synthetic disease-modifying antirheumatic drug (DMARD) incomplete response or failure, either a JAK inhibitor or a biologic would be an appropriate therapy.

That change levels the playing field for both classes, and this is very exciting to me. Both of these classes would be recommended over triple therapy with hydroxychloroquine, sulfasalazine, and methotrexate. Based on the rapidity and persistence of the response with biologics and JAK inhibitors, these therapies were conditionally recommended. I think this is important, and it also aligns with the 2019 update of the European League Against Rheumatism (EULAR) recommendations.

Both EULAR and ACR included one caveat concerning the potential venous thromboembolism (VTE) risk suggested with JAK inhibitors. They point out that, in patients at high risk for VTE, biologics might be a more appropriate therapy.

Cycling or Switching?
One question that the new ACR recommendations addressed is whether to cycle through TNF inhibitors. Well, historically, we did exactly that—cycle to another TNF inhibitor if the first one failed. Patients would respond to a different TNF inhibitor, although not as robustly and not for as long as the initial TNF inhibitor.

However, based on growing data from observational studies and randomized clinical trials, we now think that if a patient’s RA does not adequately respond to one mechanism of action such as a TNF inhibitor, they will probably do better if you move on to a second mechanism of action.

This strategy of switching out of class was conditionally recommended by the committee, particularly for patients who had failed a biologic DMARD or targeted synthetic DMARD such as a JAK inhibitor. I think this aligns with what we’re seeing in practice, and how we’re managing our patients in the clinics today.

Tapering?
Another interesting recommendation in the new guidelines concerns stopping therapy in patients receiving combination therapy with a biologic and conventional synthetic DMARD. In contrast to what EULAR had recommended—they suggested tapering the more expensive therapy—the ACR committee conditionally recommends tapering the conventional synthetic DMARD. I think the primary rationale was that, if you added the biologic to the conventional synthetic DMARD to get the RA under control, how can you remove the biologic and expect the RA to stay under control?

At this year’s ACR meeting, Curtis and colleagues presented data that confirmed that patients receiving combination therapy did not maintain low disease activity if the biologic was removed, whereas almost twice as many people did maintain low disease activity if the conventional synthetic DMARD was removed.

This is what I see in clinic as well. My patients don’t like being on combination therapy. They don’t particularly like taking conventional synthetic DMARDs, predominantly methotrexate, and they vote with their feet. Sometimes I ask them how they’re doing on their methotrexate and JAK inhibitor therapy, and they say that they stopped methotrexate 3 months ago and they are maintaining their benefit.

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What are your thoughts on the place of JAK inhibitors in the treatment of RA? Please answer the polling question and share your thoughts in the comments box below.

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In your practice, what would you recommend for most patients with RA after failure of a JAK inhibitor?
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