Background/Purpose: Filgotinib (FIL), an oral, selective, Janus Kinase 1 (JAK1) inhibitor was effective in phase 2 studies of active RA in patients (pts) with insufficient response to MTX, warranting further evaluation in phase 3.

Methods: In this global, phase 3 study (ClinicalTrials.gov Identifier: NCT02873936), pts with moderately-to-severely active RA and an inadequate response or intolerance to 1 or more prior biologic DMARDs (bDMARDs), were randomized 1:1:1 to once daily FIL 200 mg, 100 mg, or placebo (PBO) for 24 weeks; pts were required to continue stable conventional synthetic DMARDs. The primary endpoint was the proportion of subjects who achieved an ACR20 response at Week (Wk) 12.

Results: Baseline characteristics of the 448 pts randomized and treated with the study drug (FIL 200 mg, n=147; FIL 100 mg, n=153; and PBO, n=148) included: 80.4% female; 23.4% ≥ 3 prior bDMARDs; 56 yrs mean age; 12.4 yrs RA disease duration; 27 of 68 tender joint count; 17 of 66 swollen joint count; and 5.9 DAS28(CRP). At Wk 12, an ACR20 response was achieved by more pts receiving FIL 200 mg or 100 mg than PBO (66.0, 57.5 and 31.1%, respectively; both p<0.001) (Table 1). The reduction from baseline in HAQ-Disability Index (HAQ-DI) at Wk 12 was greater in the FIL 200 mg and 100 mg groups compared to the PBO group (-0.55 and -0.48 vs -0.23, respectively; both p<0.001). Other key secondary endpoints, including SF-36 and FACIT-Fatigue, were also met at both FIL doses (Table 1).

Adverse event (AE) rates were similar for FIL 200 mg, FIL 100 mg and PBO groups (69.4% and 63.4% vs 67.6%, respectively) as were rates of serious AEs (4.1%, 5.2% and 3.4%, respectively) (Table 2). There were 4 cases of uncomplicated herpes zoster (2 in each FIL group). There was one non-serious AE of retinal vein occlusion in the FIL 200 mg group; no other venous thrombotic events were reported. Two adjudicated MACE were reported: subarachnoid hemorrhage in the PBO group and myocardial ischemia in the FIL 100 mg group. There were no cases of opportunistic infection/active TB, malignancy, GI perforation or death.  

Conclusion: In this phase 3 study of pts with highly active RA and prior inadequate response/intolerance to bDMARDs, treatment with FIL over a 24-week period was associated with significant improvement in the signs and symptoms of RA, with a safety profile consistent with Phase 2 data. FIL may provide a novel treatment option for pts who continue to have active RA despite prior biologic therapies.

This study was sponsored by Gilead Sciences, Inc.