Filgotinib Effective in Refractory RA, Study Finds

Troy Brown, RN

July 23, 2019

Patients with treatment-refractory active rheumatoid arthritis (RA) who received the experimental Janus kinase 1 (JAK1) inhibitor filgotinib were more likely to achieve a clinical response at week 12 compared with patients who received placebo, new data show.

However, one expert cautions that the drug may be too expensive for many patients, and its longer-term safety and efficacy are still unclear.

Results from the FINCH 2 trial, conducted by Mark C. Genovese, MD, from the Division of Immunology and Rheumatology, Stanford University School of Medicine, Palo Alto, California, and colleagues, were published online today in JAMA.

The researchers enrolled 449 patients from 114 sites internationally for the randomized, placebo-controlled phase 3 trial. To be eligible, patients had to have had an inadequate response or be intolerant to one or more biologic disease-modifying antirheumatic drugs (bDMARDs) and were continuing treatment with a conventional synthetic DMARD. The investigators randomly assigned participants to receive filgotinib 200 mg (n = 148), filgotinib 100 mg (n = 153), or placebo (n = 148) once daily by mouth.

Patients who were deemed responders at week 14 continued to take their assigned study drug in a blinded manner through week 24. Efficacy and adverse events (AEs) were evaluated at day 1 and weeks 2, 4, 8, 12, 14, 16, 20, and 24 (or early termination).

Patients who received filgotinib 200 mg (66.0%) or 100 mg (57.5%) were more likely to achieve a 20% improvement in American College of Rheumatology criteria (ACR20) at 12 weeks, compared with those in the placebo group (31.1%). The difference between the filgotinib and placebo groups was 34.9% (95% confidence interval [CI], 23.5% – 46.3%) in the high-dose group and 26.4% (95% CI, 15.0% – 37.9%) in the low-dose group. Both were significant improvements (for both, P < .001).

Similar response rates were seen in the subset of patients with prior exposure to at least three bDMARDs (70.3%, 58.8%, and 17.6%, respectively).

Secondary efficacy endpoints included change from baseline in Health Assessment Questionnaire–Disability Index score, the proportion of patients

with disease activity score in 28 joints count using C-reactive protein (DAS28-CRP) of 2.6 or less at week 24, and the change from baseline in the 36-Item Short-Form Health Survey Physical Component and Functional Assessment of Chronic Illness Therapy–Fatigue scores at week 12.

"All hierarchically tested secondary end points (ACR response, DAS28-CRP, Simplified Disease Activity Index, Clinical Disease Activity Index, and individual ACR core set parameters) demonstrated significant improvements vs placebo in patients who had active RA despite prior bDMARD therapy," the investigators write.

The most common AE for patients taking filgotinib 200 mg was nasopharyngitis (10.2%). For those taking 100 mg, the most frequently seen AEs were headache, nasopharyngitis, and upper respiratory infection (5.9% each). The most common AE for those in the placebo group was RA (6.1%).

Study limitations include the 24-week length of the study, which does not allow for assessment of the drug's longer-term safety and benefit. In addition, the study did not use radiographic endpoints for evaluation of structural joint damage, and the study population only included those with refractory RA after bDMARD therapy. The results may not be generalizable to populations outside North America and Western Europe.

The authors note, however, that the FINCH 1 and FINCH 3 studies are investigating AEs, efficacy, and radiographic endpoints in other patient populations. As reported previously, preliminary data from the FINCH 1 trial showed filgotinib to be noninferior to adalimumab and methotrexate for patients who had an inadequate response to methotrexate alone.

Unlike bDMARDs, JAK inhibitors can be given orally, Jasvinder A. Singh, MBBS, MPH, from Birmingham Veterans Affairs Medical Center and the University of Alabama at Birmingham, writes in an accompanying editorial. "However, the risk profile of filgotinib and other JAK inhibitors is more similar to the biologic DMARDs rather than the conventional DMARDs, such as methotrexate, with comparable risks of serious infections, herpes zoster, and opportunistic infections."

Given the short duration of the FINCH 2 trial, safety data will have to come from other randomized trials and from postmarketing studies, Singh notes. In the meantime, the efficacy data from FINCH 2 are valuable.

"Having more viable treatment options for refractory RA is highly desirable. RA is a heterogeneous disease, and a significant proportion of patients with RA are either nonresponders or are intolerant to all current therapies," he writes.

"However, to help promote use, these oral JAK inhibitor therapies will need to be priced at levels comparable with the conventional synthetic DMARDs rather than the biologics. Patients and clinicians express frustration over the high pricing of new RA therapies because a portion of the cost is often passed on to the patients by the health insurance plan, which limits access to these therapies," Singh continues.

"Head-to-head comparison of filgotinib with other JAK inhibitors, biologic DMARDs, and triple conventional DMARD therapy will further define the most appropriate use of filgotinib for patients with RA by examining the comparative efficacy and safety," he writes.

The study was supported by Gilead Sciences, Inc. The study authors' and the editorialist's relevant financial relationships are listed in the original articles.

JAMA. Published online July 23, 2019. Abstract, Editorial

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