Background Filgotinib (GLPG0634, GS-6034) is an oral, selective JAK1 inhibitor that has shown a favorable safety and efficacy profile both as add-on to methotrexate (MTX) and as monotherapy in two 24-week placebo-controlled phase 2B studies in active rheumatoid arthritis (RA) patients with inadequate response to MTX (MTX-IR)1,2.
Objectives To assess effect of baseline serum CRP levels on clinical efficacy in MTX-IR RA patients treated with filgotinib.
Methods Patients were randomized in a double blind manner to placebo (PBO) or one of 3 daily doses of filgotinib (50mg, 100mg or 200mg) for 24 weeks. In the DARWIN 1 study, filgotinib on the background of MTX was evaluated as once (QD) or twice daily treatment. In the DARWIN 2 study once-daily filgotinib was assessed as monotherapy. The inclusion criterion for CRP was amended during the studies and decreased over time from 13.5 mg/L to 6.3 mg/L. This post hoc analysis included patients treated with the selected Phase 3 filgotinib doses, 100mg and 200mg QD, and PBO. Efficacy outcomes were analyzed by baseline CRP level (low: ≤9 mg/L and high: >9 mg/L, with 9mg/L as ULN).
Results Baseline disease activity was high, with mean DAS28(CRP) scores of 5.6 and 5.7 in the low CRP subgroups for DARWIN 1 and DARWIN 2, respectively, and 6.3 in the high CRP subgroups for both studies. Mean CRP levels at baseline were elevated (16.3 - 35.3 mg/L). In both low and high CRP subgroups, patients on filgotinib 100mg or 200mg QD for 12 weeks showed efficacy over PBO, as measured by change from baseline in DAS28(CRP), CDAI and HAQ-DI, and ACR20 (Table 1). Despite slight numerical differences, baseline CRP level had no consistent effect on filgotinib efficacy, neither for endpoints including CRP (DAS28(CRP) or ACR20) nor for endpoints not including CRP (CDAI). Results were similar across both studies.
Conclusions Post hoc analysis of two Phase 2B studies in MTX-IR RA patients suggests that filgotinib treatment once daily at 100mg and 200mg both on the background of MTX and as monotherapy is consistently associated with improved clinical outcomes compared to placebo, regardless of baseline CRP levels.
Westhovens R et al. Ann Rheum Dis 2016;0:1–11.
Kavanaugh A et al. Ann Rheum Dis 2016;0:1–11.
Disclosure of Interest R. Westhovens Grant/research support from: Roche, Consultant for: Galapagos, Speakers bureau: BMS, A. Kavanaugh Consultant for: Galapagos, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, C. Jamoul Employee of: Galapagos NV, C. Tasset Employee of: Galapagos NV, P. Harrison Employee of: Galapagos NV, A. Van der Aa Employee of: Galapagos NV