Effect of Filgotinib on Pain in Patients with Rheumatoid Arthritis: Results from Phase 3 Clinical Trials

Abstract

Background/Purpose: RA patients (pts) often suffer substantial pain despite ongoing treatment (tx) and regard pain control as a top tx goal. Filgotinib (FIL)—a potent, oral Janus kinase-1 selective inhibitor—was efficacious and generally well tolerated in the FINCH phase 3 RA clinical trial program.1,2 A post hoc analysis of FINCH studies was conducted to assess the impact of FIL on pain.

Methods: All pts met 2010 ACR/EULAR criteria for RA. In FINCH 3 (F3), MTX-naïve RA pts received FIL 200 mg + MTX, FIL 100 mg + MTX, FIL 200 mg monotherapy, or MTX monotherapy for up to 52 weeks (W). Pts in FINCH 1 (F1) had active RA and inadequate response to MTX (MTX-IR) and received FIL 200 mg, FIL 100 mg, adalimumab (ADA) 40 mg, or placebo (PBO) on a background of MTX for up to 52W; at W24, PBO pts were rerandomized to FIL 200 or 100 mg. In FINCH 2 (F2), pts receiving conventional synthetic (cs)DMARDs who had an inadequate response or intolerance to biologic DMARD (bDMARD-IR) received FIL 200 mg, 100 mg, or PBO on a background dose of csDMARD(s) for up to 24W.

Each study was analyzed separately. Pt-reported pain was assessed on a visual analog scale (VAS). Proportions of pts achieving thresholds of 30% (defined as “moderate clinically important differences”) and 50% (“substantial improvements”)3 reduction from baseline were analyzed, as were exploratory thresholds of 70% and 90%, and residual VAS pain scores of ≤10/20/40 mm out of 100 mm. P-values were calculated from the logistic regression with tx groups and stratification factors in the model. Comparisons were not adjusted for multiplicity; nominal P values are presented and should be interpreted as exploratory.

Results: Median duration of RA since diagnosis was 0.3–0.4 years (y) in F3, 4.8–5.8y in F1, and 9.8–10.3y in F2. Baseline pain was high among all arms (mean VAS scores of 64–68 mm across studies). Pain improved across pt populations from MTX-naïve to bDMARD-IR during tx. At W2, the percent of pts with pain reduction ≥30%, ≥50%, and residual pain ≤40 mm was significantly greater for all FIL arms compared with PBO (F1/F2) or MTX (F3) (nominal P < 0.05; Table 1). Pain was reduced by ≥90% by W52 in approximately 25% of pts in F1/F3 (Table 1). Except for pts receiving FIL 100 mg in the ≥30% reduction analysis, significantly more bDMARD-IR pts receiving FIL had pain reduction at W24 compared with PBO in all analyses (F2; nominal P < 0.05; Table 1). FIL + MTX significantly reduced pain in MTX-naïve pts vs MTX monotherapy (F3; nominal P < 0.05 for FIL 200 for all measures and time points and for FIL 100 for several measures and time points; Table 1). Overall, more pts with MTX-IR (F1) receiving FIL had greater pain reduction and lower residual pain vs pts receiving ADA, with significant differences noted for FIL 200 (but not FIL 100) for some measures at W2–W30 (nominal P < 0.05; Table 1; Fig 1; Fig 2).

Conclusion: FIL 200 and 100 mg provided rapid, clinically meaningful pain relief among a broad spectrum of RA pts and across several measures. The degree of improvement was substantial for many pts; ≥40% of pts in all studies had a ≥50% reduction in pain.