Background Filgotinib (GLPG0634) is a novel oral, selective JAK1 inhibitor that was evaluated in a 24-week phase 2B study as monotherapy in active rheumatoid arthritis (RA) with inadequate response to methotrexate. The primary endpoint of proportion of patients achieving ACR20 response after 12 weeks of treatment was met.
Objectives To present the results of the 24-week analysis.
Methods Patients with active RA were randomized 1:1:1:1 in a double blinded manner to receive either placebo (PBO) or one of three doses of filgotinib (50mg, 100mg or 200mg) as a once daily regimen for 24 weeks (DARWIN 2 study). At Week 12 all patients on PBO and on 50mg daily whose tender and swollen joint counts did not improve by at least 20% (non-responders (NR)) were reassigned to 100mg daily.
Results Of 283 randomized and treated patients, mean duration of RA of 9 years and DAS28(CRP) at baseline between 6.0–6.2. At Week 12, a statistically significant higher ACR20, ACR50, ACR70, DAS28(CRP) and CDAI response versus PBO was observed in filgotinib groups. These responses were similar or continued to improve through 24 weeks (Table 1). Increase in filgotinib dose from Week 12 improved efficacy in PBO and 50mg NR groups (at Week 24 ACR20 55% and 60% respectively). Serious Adverse Events and Treatment-Emergent Adverse Events (TEAE) were distributed over the dose groups including PBO: TEAE 39% PBO and 41% filgotinib groups. Infections occurred in 10% PBO and 19% filgotinib groups. No opportunistic infections, cancers or deaths occurred. In filgotinib groups, for the first 4 weeks, a dose dependent decrease in mean neutrophil and a small reduction in platelet counts was seen; mild increase in mean creatinine was apparent. These changes subsequently plateaued and remained stable up to Week 24. A dose dependent increase in haemoglobin was seen during the first 12 weeks and levels remained stable up to Week 24. Over 24 weeks no meaningful difference in transaminase changes was apparent.
Conclusions Significant improvement in signs and symptoms of active RA was observed after 12 weeks treatment with filgotinib monotherapy. Efficacy responses were sustained or increased at Week 24. The safety profile was acceptable.
Disclosure of Interest A. Kavanaugh Grant/research support from: Galapagos, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, Consultant for: Galapagos, Pfizer, AbbVie, Amgen, Celgene, Janssen, Novartis, Eli Lilly, UCB, L. Ponce Grant/research support from: Galapagos NV: DARWIN 2 investigator, BMS, Pfizer, R. Cseuz Grant/research support from: Galapagos NV: DARWIN 2 investigator, O. Reshetko Grant/research support from: Galapagos NV: DARWIN 2 investigator, M. Stanislavchuk: None declared, M. Greenwald Grant/research support from: Galapagos NV: DARWIN 2 investigator, A. Van der Aa Employee of: Galapagos NV, F. Vanhoutte Shareholder of: Galapagos NV, Employee of: Galapagos NV, C. Tasset Employee of: Galapagos NV, P. Harrison Employee of: Galapagos NV