Background/Purpose: Filgotinib (GLPG0634) is a novel oral, potent and selective JAK1 inhibitor that showed rapid and sustained improvements of signs and symptoms of active rheumatoid arthritis (RA) in patients with inadequate response to methotrexate (MTX) in two 24-week Phase 2B studies, with an acceptable safety profile. The effect of filgotinib add-on to MTX or monotherapy on patient-reported outcomes (PROs) is presented here.

Methods:  In DARWIN 1 (add-on to MTX) and DARWIN 2 (monotherapy), patients with active RA were randomized in a double blinded manner to placebo (PBO) or one of the three daily doses of filgotinib (50mg, 100mg or 200mg) for 24 weeks. In DARWIN 1, once (qd) and twice daily (bid) regimens were assessed. At week 12, patients on PBO (in DARWIN 1) and 50mg daily dose (in DARWIN 1 and DARWIN 2) whose tender and swollen joint counts did not improve by at least 20% were reassigned to 100mg daily dose. In DARWIN 2, all patients on PBO were reassigned to 100mg daily dose. Assessed PROs were patient evaluation of disease activity & pain, physical function, fatigue and HRQoL-SF36. This presentation reports results of the Phase 3 filgotinib doses, 100mg and 200mg qd.

Results: In total 594 and 283 patients were randomized and dosed in DARWIN 1 and DARWIN 2, respectively. Mean HAQ-DI baseline value was 1.74 and 1.81, respectively, indicating severe impairment. Filgotinib was associated with rapid and statistically significant improvement in PROs (patient assessment of disease activity and pain, physical function, fatigue and HRQoL-SF36) in both studies. The 200mg daily dose showed statistically significant effects as early as week 1-2 on HAQ-DI and patient VAS for global disease and pain, and from week 4 for FACIT and SF-36-PCS. With the 100mg qd dose, patient global assessment significantly improved from week 1-2 and FACIT from week 4 in both studies. SF-36 PCS improved from week 4 in DARWIN 2. After week 12, these responses were maintained or continued to improve through 24 weeks. At week 24, the clinical effect was comparable between filgotinib 100mg qd and 200mg qd and between add-on and monotherapy (between study comparison). Table 1. PRO responses for the 100mg and 200mg once daily doses

_{* p< 0.05 ; ** p<0.01; *** p<0.001 vs. PBO Subjects who switched at wk 12 were handled as if they discontinued at wk 12 In DARWIN 2 statistical comparison vs. PBO is not possible after wk 12}

Conclusion:  In the DARWIN 1 and DARWIN 2 studies, filgotinib led to a rapid decrease in disease burden as demonstrated by the significant improvement in all assessed PROs. After 24 weeks of treatment, filgotinib 100mg qd or 200mg qd in combination with MTX or as monotherapy demonstrated comparable benefit in improving PROs in patients with active RA and the 200 mg qd dose was associated with a faster onset of action.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-effect-of-filgotinib-glpg0634-an-oral-jak1-selective-inhibitor-on-patient-reported-outcomes-results-from-two-24-week-phase-2b-dose-ranging-studies/