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JAK Inhibitors

CME

EULAR 2020: New Data on JAK Inhibitors for Patients With RA

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

Released: July 16, 2020

Expiration: July 15, 2021

Eric M. Ruderman
Eric M. Ruderman, MD
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Despite restructuring as a virtual conference, a great deal of very real data was presented at the 2020 EULAR e-Congress, including data on the safety and efficacy of the newer JAK inhibitor therapies in rheumatoid arthritis (RA). Here are the studies that I thought were most interesting.

SELECT-CHOICE: Upadacitinib After Biologics
One of the more eagerly awaited trials presented at the meeting was the randomized phase III SELECT-CHOICE study, comparing upadacitinib and abatacept therapy in patients with RA and inadequate response or intolerance to a biologic disease-modifying antirheumatic drug (DMARD). Although previous analyses of registry data have explored the comparative efficacy of a second biologic after failure of a first, this was the first prospective head-to-head trial of this therapeutic approach in patients with RA. In this trial, 612 patients were randomized 1:1 to receive upadacitinib 15 mg PO daily or abatacept IV at the approved weight-based dose, while receiving blinded placebo for the other drug and continuing stable background DMARDs. The study met its primary endpoint: noninferiority in change from baseline in Disease Activity Score 28 (DAS28) with C-reactive protein for upadacitinib at Week 12. Upadacitinib also met the threshold for superiority at this time point, and it was associated with a statistically superior likelihood of achieving clinical remission by DAS28 criteria. Serious adverse events, serious infections, and opportunistic infections were numerically more frequent in the upadacitinib arm, whereas 4 cases of herpes zoster were reported in each arm.

FINCH 1: Filgotinib After Methotrexate
In a second comparative, randomized phase III trial, FINCH 1, 1755 patients with RA and an inadequate response to methotrexate were randomized to one of 2 doses of filgotinib (100 mg or 200 mg daily), adalimumab, or placebo. At Week 24, patients in the placebo arm were re-randomized to one of the 2 filgotinib arms. In the Week 52 analysis presented at EULAR 2020, 1417 patients remained on therapy, with similar ACR 20, 50, and 70 responses in the 2 filgotinib arms as well as the adalimumab arm. The higher dose of filgotinib was numerically superior for other outcomes, including a small but statistically significant superiority in DAS28 remission and low disease activity rates.

JAK-pot: Real-World JAKs
Additional registry data on the efficacy of JAK inhibitors in RA was also presented at the virtual meeting. The JAK-pot collaboration reported on 25,521 patients from 19 international registries initiating therapy with inhibitors of JAKs, TNF, or IL-6 as well as abatacept. In this real-world data set, JAK inhibitors tended to have a longer retention rate (a surrogate for efficacy) than the other drugs, although the difference was not statistically significant.

All in all, the efficacy data presented on JAK inhibitors provides more evidence of their effectiveness and utility across the spectrum of patients with RA, from methotrexate inadequate responders, to biologic inadequate responders, and even to DMARD-naive patients.

Adverse Events With JAK Inhibitors
At EULAR 2020, we also saw data regarding 2 specific adverse events of concern with JAK inhibitors: herpes zoster and venous thromboembolism.

Herpes Zoster
We know that herpes zoster is more common in patients with RA vs the general population, which can lead to postherpetic neuralgia. Data from 12,470 patients in the German RABBIT registry was used to compare incidence rates of herpes zoster among patients receiving JAK inhibitors, biologics, and conventional synthetic DMARDs. Compared with conventional synthetic DMARDs, JAK inhibitors were associated with a 5-fold increase in the crude incidence of herpes zoster. Biologics, regardless of mechanism, were also associated with increased crude incidences of herpes zoster, although the increase was numerically smaller.

In a separate analysis of data from the SELECT clinical trial program of upadacitinib in RA, the only clear risk factors for herpes zoster in patients receiving upadacitinib were trial participation at Asian sites and a prior history of herpes zoster. Concomitant corticosteroid or methotrexate use were not associated with increased risk, and an age of 65 years or older was associated with a small increase in risk only with the unapproved 30-mg dose of upadacitinib.

Venous Thromboembolism
Finally, in an analysis from the World Health Organization’s global safety database, patients with reported venous and pulmonary thromboembolic events while receiving tofacitinib or baricitinib tended to be older, to be receiving prothrombotic medications (eg, oral contraceptives), or to be at greater risk as indicated by concomitant use of antithrombotic therapy.

As additional data are reported on JAK inhibitors, we have not seen new safety signals not previously identified. Zoster remains a particularly important concern, even more than with biologic DMARDs, but this can be mitigated with the newer zoster vaccine. Venous thromboembolisms do remain a clinical concern, although additional information is needed to determine whether any risk is truly a class effect or may vary among the molecules and whether specific patients can be identified as having particularly higher risk.

Your Thoughts?
How will new data from EULAR 2020 influence your practice with JAK inhibitors for patients with RA? Join the discussion by posting a comment below. For more coverage of RA from the virtual meeting, download focused Capsule Summaries of key studies and use the slides in your own presentations.

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Based on new data from EULAR 2020, how comfortable would you be prescribing a JAK inhibitor for a patient with RA and an inadequate response to a previous biologic therapy?
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