OP0224 Filgotinib (GLPG0634), An Oral Jak1 Selective Inhibitor Is Effective in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: Results from A 24-Week Phase 2B Dose Ranging Study: Table 1.

Abstract

BackgroundFilgotinib (GLPG0634) is a novel oral selective JAK1 inhibitor that was evaluated in a 24-week phase 2B study in combination with methotrexate (MTX) in active rheumatoid arthritis (RA) with inadequate response to MTX. The primary endpoint of proportion of patients achieving ACR20 response after 12 weeks of treatment was met.ObjectivesTo present the results of the 24-week analysis.MethodsPatients with active RA on stable dose of MTX were randomized 1:1:1:1:1:1:1 in a double blinded manner to receive either placebo (PBO) or one of three doses of filgotinib (50mg, 100mg or 200mg) as once (qd) or twice daily (bid) regimen for 24 weeks (DARWIN 1 study). At Week 12, patients on placebo and 50mg dose whose tender and swollen joint counts did not improve by 20% (non-responders (NR)) were reassigned to 100mg daily.Results594 randomized and treated patients, mean duration of RA of 7–10 years and mean DAS28(CRP) at baseline 6.0–6.2. At Week 12, statistically significant and dose dependent higher ACR20, ACR50, ACR70, DAS28(CRP) and CDAI responses versus PBO were observed in patients on filgotinib. These responses were maintained or continued to improve through 24 weeks (Table 1). Increase in filgotinib dose from Week 12 lead to improved efficacy in PBO and 50mg NR groups (at Week 24 ACR20 57% and 42% respectively). Serious Adverse Events and Treatment-Emergent Adverse Events (TEAE) were distributed over the groups including PBO: TEAE 51% PBO and 52% filgotinib groups. No opportunistic infections or cancers occurred; one death was reported. Infections occurred in 19% PBO and 25% filgotinib groups. Laboratory parameters remained stable between 12 and 24 weeks. Increase in haemoglobin was noted in patients on filgotinib.Table 1.Summary of the efficacy responses after 12 and 24 weeks treatmentOnce-daily dosingTwice-daily dosingPlacebo50mg100mg200mg25mg50mg100mgn=86n=82n=85n=86n=86n=85n=84Week 12 ACR20, NRI1, %445664*69**576079*** ACR50, NRI, %1533*38**43***28*34*55*** ACR70, NRI, %8162124*141931** DAS28(CRP), mean change from BL2, LOCF3−1.2−1.8**−2.2***−2.5***−1.9**−2.1***−2.8*** CDAI4, mean change from BL, LOCF−17−20−24**−26***−21*−23**−29***Week 24 ACR20, NRI, %425561*73***5660*80*** ACR50, NRI, %1635**47***50***35**35**55*** ACR70, NRI, %922*33**29**21*24*39*** DAS28(CRP), mean change from BL, LOCF−1.2−2.0***−2.7***−2.8***−2.2***−2.4***−3.2*** CDAI, mean change from BL, LOCF−16−21**−29***−29***−24***−27***−32****p<0.05 vs. placebo; **p<0.01 vs. placebo; ***p<0.001 vs. placebo; ACR scores based on ITT analysis. 1Non-responder imputation. 2Baseline. 3Last observation carried forward. 4Clinical Disease Activity Index.ConclusionsSignificant improvement in signs and symptoms of active RA was observed after 12 weeks and sustained or increased up to Week 24 with filgotinib in combination with MTX. The safety profile was overall acceptable.Disclosure of InterestR. Westhovens Grant/research support from: Roche, BMS, Janssen, Galapagos NV: investigator DARWIN 1, R. Alten Grant/research support from: Galapagos NV: investigator ...

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