Background/Purpose: Filgotinib (GLPG0634) is a novel oral, potent and selective JAK1 inhibitor that has previously demonstrated efficacy in combination with methotrexate (MTX) in treating rheumatoid arthritis (RA) in 4-week phase 2A studies with an acceptable safety profile. The purpose of this study was to evaluate efficacy and safety of different doses of filgotinib as monotherapy versus placebo (PBO) in patients with active RA with inadequate response to MTX.

Methods: Patients with active RA were randomized 1:1:1:1 in a double blinded manner to receive either PBO or one of three doses of filgotinib (50mg, 100mg or 200mg) as once daily regimen for 24 weeks (DARWIN 2 study).  The primary endpoint was the proportion of patients achieving ACR20 response at week 12. Reported data are from the planned 12 weeks analysis.

Results: Of 283 randomized and treated patients, 76-87% were females with mean age across groups of 52-53 years, mean duration of RA of 9 years and DAS28(CRP) at baseline ranging from 6.0-6.2. Patients were well distributed across geographical regions. At week 12, a statistically significant higher ACR20 response versus PBO was observed with all three doses tested versus PBO. For other key efficacy endpoints (ACR50, ACR-N, DAS28 (CRP), CDAI, SDAI) all doses showed significant difference versus PBO.  By week 12, 24-45% of patients on filgotinib achieved low disease activity (DAS28(CRP)≤ 3.2) in a dose dependent manner, compared to 14% in PBO. Onset of efficacy was rapid for ACR-N and DAS28(CRP) with statistically significant differences at 100mg and 200mg daily dose seen from week 1 onwards.

Table 1. Summary of the ACR/DAS28(CRP)/CDAI responses after 12 weeks treatment:

*p< 0.05 vs. placebo; **p<0.01 vs. placebo; ***p<0.001 vs. placebo.  ACR scores based on ITT analysis. ¹Non-responderimputation. ²Last observation carried forward. ³Baseline. ⁴Clinical Disease Activity Index

Over 12 weeks, Serious Adverse events (2%) and Treatment-Emergent Adverse events (TEAE) were distributed across the groups including placebo: 38% patients on PBO and 31-42% in the filgotinib groups experienced TEAES. Most of the TEAEs were mild. In the filgotinib groups, a dose dependent decrease in mean neutrophil as well as a small reduction in platelet counts was seen without discontinuations and mild increase in mean creatinine concentration was apparent. Notably, a dose dependent increase in haemoglobin concentration was detected and no meaningful difference in transaminase changes was encountered with filgotinib.

Conclusion: Over 12 weeks, filgotinib as monotherapy demonstrated clear efficacy in treating the signs and symptoms of active RA with a rapid onset of action. Overall safety profile was favorable and consistent with previous studies conducted in RA with filgotinib.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/filgotinib-glpg0634-an-oral-jak1-selective-inhibitor-is-effective-as-monotherapy-in-patients-with-active-rheumatoid-arthritis-results-from-a-phase-2b-dose-ranging-study/