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Northwestern University Feinberg School of Medicine
Clinical Practice Director
Northwestern Medical Group
Eric M. Ruderman, MD, has disclosed that he has received consulting fees from AbbVie, Amgen, Gilead Sciences, Janssen, Lilly, Novartis, Pfizer, and Selecta.
As more biologic disease-modifying antirheumatic drugs (bDMARDs) and targeted small-molecule DMARDs become available for the treatment of rheumatoid arthritis (RA), we are faced with both more choices for initial treatment and challenging management decisions for patients in whom these therapies have failed. Recent data presented at the 2020 EULAR e-Congress may help us better understand and make treatment choices for this important patient population.
SELECT-CHOICE: Upadacitinib Safety After Previous bDMARDs
The highly anticipated phase III SELECT-CHOICE trial demonstrated both noninferiority and superiority of upadacitinib vs abatacept in change from baseline in DAS28(CRP) at Week 12 in patients with RA failing biologics, with upadacitinib further showing statistical superiority for other endpoints (eg, CDAI/SDAI remission, ACR/EULAR Boolean remission, ACR50, and ACR70).
These efficacy findings were notable, but what struck me were the safety outcomes.
The comparator abatacept is sometimes believed to be associated with fewer infectious adverse events than other biologics. Indeed, in this trial, the upadacitinib arm had numerically more frequent serious infections, opportunistic infections, and serious adverse events. However, these were still uncommon. And although JAK inhibitors have been associated with herpes zoster infection, the SELECT-CHOICE investigators reported only 8 cases of herpes zoster (1.3%), and they were equally distributed between the abatacept and upadacitinib arms.
FINCH 2: Efficacy of Filgotinib Maintained Regardless of Previous bDMARDs
The phase III FINCH 2 trial compared conventional synthetic DMARDs in combination with filgotinib vs placebo in 448 patients with active RA and inadequate response to 1 or more previous bDMARDs. A subanalysis presented at EULAR 2020 looked at the response to filgotinib when stratified by the mechanism of action and number of previous bDMARDs.
To me, the data suggest that filgotinib, if approved, will be an appropriate option regardless of previous bDMARD use.
Whereas patients treated with either 1 or 2 previous bDMARDs achieved DAS28(CRP) ≤ 3.2 at a higher rate with filgotinib than those with ≥ 3 previous bDMARDs, the difference in response with filgotinib vs placebo was comparable regardless of the number of previous bDMARDs.
In addition, the difference in response was similar in those who had previously received a TNF vs an IL-6 inhibitor.
Safety, as assessed by adverse events, was also similar regardless of the nature or number of previous bDMARDs..
Switching JAK Inhibitors
As small-molecule DMARDs are being more widely used, rheumatologists are having to make treatment recommendations for patients with RA with previous small-molecule DMARD therapy.
A small series reported at EULAR 2020 described outcomes in 28 patients switching to a second JAK inhibitor. One half had received tofacitinib as their first JAK inhibitor and the other half had received baricitinib; 86% had previously received a bDMARD.
Of 21 patients followed out to 12 months, 13 remained on their second JAK inhibitor, and the 8 who discontinued did so for lack of efficacy. The likelihood of continuing the second JAK inhibitor was similar regardless of whether the first JAK inhibitor was discontinued for inefficacy or adverse events.
These data, although preliminary, suggest that switching to a second JAK inhibitor after failure of a first may be an appropriate option in clinical practice.
Sequencing JAK Inhibitors After bDMARDs
We now have data showing that JAK inhibitors can be successfully used after bDMARDs in practice, at least based on continuation rates. At EULAR 2020, investigators presented the first analysis from JAK-POT, a consortium of 17 international registries of more than 25,000 patients with RA being treated with bDMARDs or JAK inhibitors.
These real-world data showed that persistence on drug was similar between patients initiating JAK inhibitors (who had previously been treated with a higher number of bDMARDs and/or small-molecule DMARDs) and those starting therapy with abatacept or an IL-6 inhibitor. Persistence on drug was greater in those receiving a JAK inhibitor vs a TNF inhibitor.
The authors plan to explore this issue further by examining treatment response measures in the different groups.
Which new findings reported at EULAR 2020 will most influence how you manage biologic-experienced patients with RA? Join the discussion by posting a comment. 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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