Article
Filgotinib, an oral JAK1 selective inhibitor, is effective in combination with methotrexate and as monotherapy in patients with active rheumatoid arthritis: results from two Phase 2B studies (DARWIN 1 and DARWIN 2)
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Authors
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Rieke H.-E. Alten
- Schlossparkklinik, Akademisches Lehrkrankenhaus der Charité - Universitätsmedizin Berlin, Innere Medizin II, Rheumatologie, klinische Immunologie und Osteologie, Berlin
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Hans-Hartwig Euler
- Praxis, Hamburg
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René Westhovens
- University Hospitals Leuven, Leuven, Belgium
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Arthur Kavanaugh
- UCSD, Division of Rheumatology, Allergy and Immunology, La Jolla, United States of America
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Luc Meuleners
- Galapagos NV, Mechelen, Belgium
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Chantal Tasset
- Galapagos NV, Mechelen, Belgium
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Pille Harrison
- Galapagos NV, Mechelen, Belgium
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Annegret Van der Aa
- Galapagos NV, Mechelen, Belgium
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Gerd-Rüdiger Burmester
- Charité - Universitätsmedizin Berlin, Medizinische Klinik mit Schwerpunkt Rheumatologie und klinische Immunologie, Berlin
| Published: | September 4, 2017 |
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Outline
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Background: Filgotinib is an oral JAK1 selective inhibitor which was evaluated in comparison to placebo, in two 24-week Phase 2b studies in patients with active rheumatoid arthritis and inadequate response to methotrexate, as add-on to methotrexate (DARWIN 1) or as monotherapy (DARWIN 2). Results from DARWIN 1 and 2, for the 100mg and 200mg once daily (qd) dosing groups (Phase 3 doses and regimen) versus placebo are presented here.
Methods: Patients with active disease were randomized in a double blinded manner to one of the three daily doses of filgotinib (50mg, 100mg or 200mg) or placebo for 24 weeks. At week 12, patients on placebo (in DARWIN 1) and 50mg daily (in DARWIN 1 and DARWIN 2) whose tender and swollen joint counts did not improve by at least 20% were reassigned to 100mg daily. In DARWIN 2, all patients on placebo were reassigned to 100mg daily. Primary endpoint was the proportion of patients achieving ACR20 response at week 12.
Results: In total 594 and 283 patients were randomized and dosed in DARWIN 1 and DARWIN 2, respectively. Baseline characteristics were similar across groups. Primary endpoint in both studies was met. Statistically significant higher responses versus placebo were observed as of the first timepoint measured, and were maintained or continued to improve through 24 weeks. Table 1 [Tab. 1], Table 2 [Tab. 2].
In both studies, incidences of Treatment-Emergent Adverse Events (TEAE) and Serious Adverse Events were similar across groups. There were 7 serious infections (1 pbo, 6 active), 2 cases of Herpes zoster (1 pbo, 1 active), and 1 major adverse cardiac event (MACE, in active group). No opportunistic infections, active tuberculosis, malignancies, or deaths occurred. Of note, with filgotinib, haemoglobin and atherogenic index improved.
Conclusion: Filgotinib significantly improved symptoms of active rheumatoid arthritis in combination with methotrexate or as monotherapy. The overall safety profile was acceptable. A large Phase 3 program is currently ongoing.
