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)
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A Kavanaugh1, J Kremer2, L Ponce3
1University of California San Diego, San Diego, California, USA.
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.
Insights
Filgotinib, a Janus kinase 1 inhibitor, effectively treated rheumatoid arthritis (RA) symptoms in a 24-week study. The drug demonstrated a rapid onset of action and was generally well-tolerated across different doses.
Area of Science:
- Rheumatology
- Immunology
- Pharmacology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation.
- Methotrexate (MTX) is a common first-line treatment for RA, but some patients have an inadequate response.
- Janus kinase (JAK) inhibitors represent a class of targeted therapies for autoimmune conditions.
Purpose of the Study:
- To assess the efficacy and safety of various doses of filgotinib monotherapy in patients with active RA.
- To evaluate filgotinib's effectiveness in patients who previously had an inadequate response to methotrexate (MTX).
Main Methods:
- A 24-week, phase IIb, randomized, double-blind, placebo-controlled study.
- 283 patients with active RA were randomized to receive 50, 100, or 200 mg of filgotinib or placebo daily.
- The primary endpoint was the proportion of patients achieving ACR20 response at week 12.
Main Results:
- Significantly higher ACR20 response rates were observed with all filgotinib doses compared to placebo at week 12 (≥65% vs 29%, p<0.001).
- Improvements in other efficacy measures (ACR50, ACR70, DAS28-CRP, CDAI, SDAI, HAQ-DI) favored filgotinib 100 and 200 mg over placebo, with responses sustained through week 24.
- Filgotinib showed a rapid onset of action. Dose-dependent increases in hemoglobin were noted. Adverse event rates were similar between filgotinib and placebo groups, with no reported tuberculosis or opportunistic infections.
Conclusions:
- Filgotinib monotherapy demonstrated significant efficacy in treating active RA signs and symptoms over 24 weeks.
- The drug exhibited a rapid onset of action and was generally well-tolerated.
- Filgotinib offers a potential therapeutic option for RA patients with inadequate response to MTX.
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