Filgotinib Effective in RA Patients When bDMARDs Fail

Patients with active rheumatoid arthritis (RA) who are nonresponsive or intolerant to biologic disease-modifying antirheumatic drug (bDMARD) therapy may benefit from filgotinib, according to a randomized controlled trial.

“Patients with active rheumatoid arthritis (RA) despite treatment with biologic disease-modifying antirheumatic drug (bDMARD) therapy need treatment options,” the study authors wrote in JAMA. They sought “To evaluate the effects of filgotinib vs placebo on the signs and symptoms of RA in a treatment-refractory population.”

The 24-week study spanned 114 sites internationally and took place between July 2016 and June 2018. A total of 449 adult RA patients were randomized to either filgotinib 200 mg, filgotinib 100 mg, or placebo. Patients had moderately to severely active RA and had a history of inadequate response or intolerance to at least one prior bDMARD. The study’s primary outcome was the proportion of patients achieving 12-week 20% improvement in the American College of Rheumatology criteria (ACR20). Other outcomes were assessments of 12-week low disease activity (disease activity score in 28 joints–C-reactive protein [DAS28-CRP] ≤ 3.2) and 24-week remission (DAS28-CRP <2.6); adverse events; and changes in Health Assessment Questionnaire–Disability Index, 36-Item Short-Form Health Survey Physical Component, and Functional Assessment of Chronic Illness Therapy–Fatigue scores.

Of the 448 patients (mean [SD] age, 56 [12] years; 360 women [80.4%]; mean [SD] DAS28-CRP score, 5.9 [0.96]; 105 [23.4%] with ≥ 3 prior bDMARDs) treated, 381 completed the trial. After 12 weeks, ACR20 response was achieved in 66% of filgotinib 200 mg patients and 57.5% of filgotinib 100 mg patients, compared to 31.1% of placebo patients difference vs. placebo: 34.9% [95% confidence interval {CI}, 23.5%-46.3%] and 26.4% [95% CI, 15.0%-37.9%], respectively; P < 0.001 for both). Both doses of filgotinib were associated with a better response than placebo even in patients who had a history of three or more bDMARDs: filgotinib 200 mg, 70.3%; filgotinib 100 mg, 58.8%; and placebo, 17.6% (difference vs. placebo: 52.6% [95% CI, 30.3%-75.0%] for filgotinib 200 mg, and 41.2% [95% CI, 17.3%-65.0%] for filgotinib 100 mg; P < 0.001 for both). In the high-dose filgotinib group, the most common adverse event (AE) was nasopharyngitis (10.2%); for the low-dose group, the most common AEs were headache, nasopharyngitis, and upper respiratory infection (5.9% each). In the placebo group, RA was the most common AE (6.1%). In the filgotinib group, there were four cases of uncomplicated herpes zoster and one case of retinal vein occlusion. No opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations, or deaths were reported.

In sum, the authors wrote, “Among patients with active RA who had an inadequate response or intolerance to 1 or more bDMARDs, filgotinib, 100 mg daily or 200 mg daily, compared with placebo resulted in a significantly greater proportion achieving a clinical response at week 12. However, further research is needed to assess longer-term efficacy and safety.”