Background 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.
Objectives To investigate the effect of filgotinib add-on to MTX or monotherapy on patient-reported outcomes (PROs).
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.
Results In total 594 and 283 patients were randomized and treated in DARWIN 1 and DARWIN 2, respectively. Mean HAQ-DI baseline value was 1.74 and 1.81, respectively, indicating severe impairment. Filgotinib demonstrated rapid and significant improvement in PROs (patient assessment of disease activity and pain, physical function, fatigue and HRQoL-SF36) in both studies, with the 200mg daily dose showing statistically significant effects as early as week 1–2 on HAQ-DI and the patient VAS global disease and pain and from week 4 on the FACIT and SF-36-PCS. After week 12, these responses were maintained or continued to improve through 24 weeks. At week 24 with identical daily doses, the filgotinib effect was comparable between qd and bid regimens (in DARWIN 1) and between add-on and monotherapy (between study comparison)”
Conclusions 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 in combination with MTX as qd or bid or as monotherapy demonstrated comparable benefit in improving PROs in RA patients with high disease activity.
Disclosure of Interest M. Genovese Grant/research support from: Pfizer, Lilly, Vertex, Astellas, AbbVie, Consultant for: Galapagos, Gilead, Pfizer, Lilly, Vertex, Astellas, AbbVie, R. Westhovens Grant/research support from: Galapagos NV: DARWIN 1 principal investigator, Janssen, Roche, Consultant for: BMS, A. Kavanaugh Grant/research support from: Galapagos NV: DARWIN 2 principal investigator, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, Consultant for: Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, L. Meuleners Employee of: Galapagos NV, A. Van der Aa Employee of: Galapagos NV, P. Harrison Employee of: Galapagos NV, C. Tasset Employee of: Galapagos NV