Once-daily filgotinib a new option for bDMARD-refractive moderate-to-severe RA
Adults with moderate-to-severe rheumatoid arthritis (RA) with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs) may benefit from treatment with the selective Janus kinase (JAK)-1 inhibitor filgotinib, the phase III FINCH 2* trial shows.
Patients in this randomized, multinational trial had persistent moderate-to-severe RA despite treatment with conventional synthetic (cs)DMARDs and ≥1 bDMARDs (n=448, mean age 56 years, 80.4 percent female, mean DAS28-CRP** score 5.9). They received oral filgotinib at a dose of either 200 mg (n=148) or 100 mg (n=153) or placebo (n=148) once/day in addition to stable doses of 1–2 csDMARDs*** for 24 weeks. BDMARDs were discontinued ≥4 weeks pre-randomization; stable doses of glucocorticoids (≤10 mg/day of prednisone or equivalent) and/or NSAIDs were permitted.
At week 12, more filgotinib than placebo recipients achieved an American College of Rheumatology 20 percent response (ACR20; 66.0 percent [200 mg] and 57.5 percent [100 mg] vs 31.1 percent [placebo]; difference, 34.9 percent and 26.4 percent, respectively; p<0.001 for each dose vs placebo). [JAMA 2019;322:315-325]
The ACR20 achievement was particularly notable among patients who had previously received ≥3 bDMARDs (70.3, 58.8, and 17.6 percent of filgotinib 200 mg, 100 mg, and placebo recipients, respectively; difference, 52.6 percent [200 mg] and 41.2 percent [100 mg] vs placebo; p<0.001 each).
“For patients with active RA refractory to bDMARDs, subsequent treatment has generally been observed to be less effective, especially as the number of previous treatments increases,” said the authors. “Improvements in ACR20 with filgotinib were evident at week 2 [earliest assessment], and responses were maintained or improved over 24 weeks.”
“We found that [the] high levels of response [in FINCH 2] were independent of how many drugs you’d failed, and independent of which drugs you’d failed,” said study principal investigator Professor Mark Genovese from Stanford University, Stanford, California, US.
“For patients who haven’t done well on other therapies, these findings are cause for optimism, enthusiasm, and hope,” he said.
At week 12, filgotinib recipients also demonstrated greater improvements from baseline in HAQ-DI## score (difference, -0.32 [200 mg] and -0.27 [100 mg] vs placebo; p<0.001 for both) and 36-Item Short-Form Health Survey Physical Component score (p≤0.002).
More filgotinib than placebo recipients achieved DAS28-CRP ≤3.2 at week 12 (difference, 24.6 percent [200 mg] and 21.0 percent [100 mg]; p<0.001 vs placebo) and DAS28-CRP <2.6 (remission) at week 24 (difference, 18.5 percent; p<0.001 [200 mg] and 14.0 percent; p=0.003 [100 mg]).
Over 24 weeks, treatment-emergent adverse events (AEs) occurred in 69.4, 63.4, and 67.6 percent of filgotinib 200 mg, 100 mg, and placebo recipients, respectively, with 6.7 percent grade ≥3AEs. The most common AEs were nasopharyngitis in filgotinib 200 mg recipients (10.2 percent), nasopharyngitis, upper respiratory tract infection, and headache in filgotinib 100 mg recipients (5.9 percent each), and bronchitis in placebo recipients (5.4 percent). Serious AEs occurred in six, eight, and five patients, respectively, and five, six, and three patients, respectively, discontinued study drug due to AEs.
Infections occurred in 36.1, 34.0, and 25.7 percent of filgotinib 200 mg, 100 mg, and placebo recipients, respectively, though mostly non-serious AEs, and there were four cases of uncomplicated herpes zoster. No opportunistic infections, active tuberculosis, malignancies, gastrointestinal perforations, or deaths occurred, while laboratory abnormality incidence was comparable between groups.
According to the authors, studies assessing the long-term efficacy and safety of filgotinib, as well as its impact in methotrexate-naïve and poor responders are underway. Future studies should also investigate the impact of filgotinib in more diverse populations, they suggested, as FINCH 2 comprised mostly patients from North America and Western Europe.
“Having more viable treatment options for refractory RA is highly desirable,” said Dr Jasvinder Singh from the University of Alabama at Birmingham, Alabama, US, in an editorial. [JAMA 2019;322:309-311] However, he cautioned that further research is needed to identify the benefits vs risks of the different JAK inhibitors, including whether the associated AEs are medication-related, class-related, or dose-related, as well as patient populations that may be at an elevated risk of AEs.