Filgotinib (GLPG0634/GS-6034), an oral selective JAK1 inhibitor, is effective as monotherapy in patients with active rheumatoid arthritis: results from a randomised, dose-finding study (DARWIN 2)

Abstract

Objectives: To evaluate the efficacy and safety of different doses of filgotinib, an oral Janus kinase 1 inhibitor, as monotherapy in patients with active rheumatoid arthritis (RA) and previous inadequate response to methotrexate (MTX).

Methods: In this 24-week phase IIb study, patients with moderately to severely active RA were randomised (1:1:1:1) to receive 50, 100 or 200 mg filgotinib once daily, or placebo, after a ≥4-week washout from MTX. The primary end point was the percentage of patients achieving an American College of Rheumatology (ACR)20 response at week 12.

Results: Overall, 283 patients were randomised and treated. At week 12, significantly more patients receiving filgotinib at any dose achieved ACR20 responses versus placebo (≥65% vs 29%, p<0.001). For other key end points at week 12 (ACR50, ACR70, ACR-N, Disease Activity Score based on 28 joints and C reactive protein, Clinical Disease Activity Index, Simplified Disease Activity Index and Health Assessment Questionnaire-Disability Index) significant differences from baseline in favour of filgotinib 100 and 200 mg versus placebo were seen; responses were maintained or improved through week 24. Rapid onset of action was observed for most efficacy end points. Dose-dependent increases in haemoglobin were observed. The percentage of patients with treatment-emergent adverse events (TEAE) was similar in the placebo and filgotinib groups (∼40%). Eight patients on filgotinib and one on placebo had a serious TEAE, and four patients, all of whom received filgotinib, experienced a serious infection. No tuberculosis or opportunistic infections were reported.

Conclusions: Over 24 weeks, filgotinib as monotherapy was efficacious in treating the signs and symptoms of active RA, with a rapid onset of action. Filgotinib was generally well tolerated.

Trial registration number: NCT01894516.

Keywords: DAS28; Rheumatoid Arthritis; Treatment.

Conflict of interest statement

Competing interests: AK has received compensation for consultancy work, or has been involved in the conduct of clinical research studies, for AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, and has consulted for Galapagos NV. JK has received compensation for consultancy work from AbbVie, BMS, Genentech, Lilly, Novartis and Pfizer, and has received grant support from AbbVie, Genentech, Eli Lilly, Novartis and Pfizer; he is an employee of The Consortium of Rheumatology Researchers of North America. LP has received honoraria from Bristol-Myers Squibb and Pfizer. MG has been involved in clinical research studies for AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galapagos, Merck, Pfizer and UCB. RC, OVR and MS were DARWIN 2 study investigators, funded by Galapagos NV. AVdA, FV, CT and PH are employees of Galapagos NV.

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