Objectives To evaluate the efficacy and safety of different doses and regimens of filgotinib, an oral Janus kinase 1 inhibitor, as add-on treatment to methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and inadequate response to MTX.
Methods In this 24-week phase IIb study, patients with moderate-to-severe active RA receiving a stable dose of MTX were randomised (1:1:1:1:1:1:1) to receive placebo or 50, 100 or 200 mg filgotinib, administered once daily or twice daily. Primary end point was the percentage of patients achieving a week 12 American College of Rheumatology (ACR)20 response.
Results Overall, 594 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib 100 mg once daily or 200 mg daily (both regimens) achieved an ACR20 response versus placebo. For other key end points at week 12 (ACR50, ACR-N, Disease Activity Score based on 28 joints and C reactive protein value, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index), differences in favour of 100 or 200 mg filgotinib daily were seen versus placebo; responses were maintained or improved through to week 24. Rapid onset of action and dose-dependent responses were observed for most efficacy end points and were associated with an increased haemoglobin concentration. No significant differences between once-daily and twice-daily regimens were seen. Treatment-emergent adverse event rates were similar in placebo and filgotinib groups. Serious infections occurred in one and five patients in the placebo and filgotinib groups, respectively. No tuberculosis or opportunistic infections were reported.
Conclusions Filgotinib as add-on to MTX improved the signs and symptoms of active RA over 24 weeks and was associated with a rapid onset of action. Filgotinib was generally well tolerated.
Trial registration number: NCT01888874.
- Rheumatoid Arthritis
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Handling editor Tore K Kvien
Acknowledgement The authors thank the members of the DARWIN 1 study group, the contract research organisation and all patients who participated in the trial.
Contributors RW, PCT, AVdA, FV, CT and PH contributed to the conception, collation and analysis of the data. All authors contributed to the writing of the paper and participated in the review and interpretation of the data. All authors read and approved the final manuscript.
Funding The work presented here, including the conduct of the study, data analysis and interpretation, was supported by Galapagos NV. Editorial assistance in the preparation of the manuscript was provided by Fishawack Communications, which was funded by Galapagos NV.
Competing interests RW received unrestricted research grant from Roche to his institution, was advisor for Jansen (Golimumab) and part of the speaker's bureau of BMS. PCT has served as a consultant to Lilly, Galapagos and Pfizer. RA received grant support from Galapagos NV. MG has participated in clinical research studies for AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galapagos, Merck, Pfizer and UCB. FE-S, DP and MM were DARWIN 1 study investigators, funded by Galapagos NV. AVdA, FV, CT and PH are employees of Galapagos NV.
Patient consent Obtained.
Ethics approval The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, Good Clinical Practice, International Council for Harmonisation guidelines, and all applicable national and local laws and regulatory requirements.
Provenance and peer review Not commissioned; externally peer reviewed.
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