O02. FILGOTINIB, AN ORAL JAK1 SELECTIVE INHIBITOR WITH A RAPID ONSET OF ACTION: RESULTS FROM THE DARWIN 1 STUDY IN METHOTREXATE INADEQUATE RESPONSE RHEUMATOID ARTHRITIS PATIENTS

Abstract

Background: Filgotinib, an oral, selective JAK1‐inhibitor, showed sustained improvements of signs and symptoms in patients with active rheumatoid arthritis (RA) and inadequate response to methotrexate (MTX) in two 24‐week Phase 2B studies, with acceptable safety profile. The objective was to investigate speed of onset of effect of filgotinib based on clinical and patient‐reported outcome (PRO) measures in DARWIN 1 (MTX add‐on). Methods: Patients with active RA were randomized in a double‐blind manner to placebo (PBO) or one of three total daily doses of filgotinib (50mg, 100mg, 200mg) and two regimens (qd and bid) for 24 weeks. Assessed clinical measures included ACR20, ACR50 and DAS28‐ (CRP). PROs were patient's evaluation of disease activity and pain, physical function, fatigue and HRQoL‐SF36. This presentation reports results from patients dosed with filgotinib 100mg or 200mg qd (selected Phase 3 doses) or PBO. Results: 594 patients were randomized and dosed. Baseline mean DAS28‐(CRP) was 6.1 and mean HAQ‐DI was 1.7, indicating significant impairment. Rapid onset of efficacy was observed with filgotinib 100mg and 200mg, with significant differences from PBO as of week 1 for ACR20, DAS28‐(CRP) and serum CRP concentrations. Filgotinib introduced rapid and statistically significant improvement in PROs with both doses: 200mg qd showed statistically significant effects as early as week 1 for patient global disease activity, week 2 for patient pain and HAQ‐DI and week 4 (earliest timepoint measured) for FACIT and SF‐36 PCS. With 100mg qd, patient global disease activity, patient pain and HAQ‐DI significantly improved from week 2, FACIT and SF‐36 (PCS and MCS) as of week 4 (Table 1). Responses were maintained or continued to improve throughout 24 weeks treatment. Conclusion: Filgotinib 100mg and 200mg qd as add‐on treatment to MTX, led to early onset of efficacy as of week 1 and to rapid decrease in RA disease burden as demonstrated by significant improvement in PROs as of the first timepoint measured. (Table presented).