MADRID, SPAIN — The potent, orally administered, selective Janus kinase 1 (JAK1) inhibitor filgotinib (FIL) in combination with methotrexate (MTX) led to significant improvements in rheumatoid arthritis (RA) compared with MTX alone, and was well-tolerated in early active RA patients naive to MTX, according to research presented at the European League Against Rheumatism (EULAR) Congress 2019, held June 12-15, 2019, in Madrid, Spain.
This phase 3, double-blind, active-controlled, randomized study was designed to compare the efficacy and safety of FIL (with and without MTX) in patients with moderate to severe RA who were MTX treatment-naive. Participants were randomly assigned to the following groups (2:1:1:2): FIL 200 mg daily + MTX weekly (up to 20 mg), FIL 100 mg + MTX, FIL 200 mg + placebo, or MTX + placebo. Treatments continued for up to 52 weeks, and the results presented are through week 24.
The primary efficacy end point was the proportion of patients who achieved American College of Rheumatology criteria (ACR20) response at week 24, with secondary end points including ACR50 and ACR70 responses; disease activity score 28-joint count C-reactive protein (DAS28-CRP) score ≤3.2 and <2.6; and changes in van der Heijde modified total Sharp score, health assessment questionnaire disability index, short-form 36 health survey physical component score (SF-36 PCS), and functional assessment of chronic illness therapy-fatigue.
Treatment comparisons for ACR response and other binary end points were made using logistic regression adjusting for stratification factors with nonresponder imputation, and mixed-effects models adjusting for baseline values, treatment, visit, stratification factors, and treatment by visit interaction as fixed effects with observed cases were used for continuous end points.
Among the total 1252 participants, 1249 received the study drug (416 FIL 200 mg + MTX; 207 FIL 100 mg + MTX; 210 FIL 200 mg monotherapy; 416 MTX monotherapy) and were analyzed, and 1130 completed through week 24. The majority of participants (76.9%) were women, with a mean time since diagnosis of 2.2 years (median 0.4 years).
At baseline, the mean SD DAS28-CRP score was 5.7 (1.0), and 35.9% were using oral steroids. At week 24, significantly more participants achieved ACR20 response in the FIL 200 mg + MTX (81.0%; P <.001) and FIL 100 mg + MTX (80.2%; P <.05) arms compared with MTX monotherapy (71.4%).
More participants receiving FIL with or without MTX achieved ACR50 and ACR70 responses and DAS28-CRP <2.6 and ≤3.2, and reported SF-36 PCS improvements compared with MTX monotherapy. The onset of activity was rapid, with significantly more participants achieving ACR50 and DAS28-CRP <2.6 with FIL than MTX at week 2. The safety profile for FIL was consistent with prior studies through week 24.
Study investigators conclude, “The JAK1 inhibitor FIL in combination with MTX led to significant improvements in RA signs and symptoms, physical function, and patient-reported outcomes compared to MTX alone and was well tolerated in patients with early active RA naive to MTX. Clinically meaningful response to FIL occurred as early as 2 weeks after treatment initiation.”
“Despite several available medications for patients with rheumatoid arthritis, many patients do not have adequate control of their symptoms,” said John Sundy MD, PhD, Senior Vice President, Clinical Research, Inflammation, Gilead Sciences in an emailed response to Rheumatology Advisor. “We are excited about the results of FINCH 3, which show efficacy across various criteria including ACR20, ACR50, ACR70 and remission, and a safety profile consistent with prior results for filgotinib.”
Disclosure: Multiple authors disclosed affiliations with pharmaceutical companies. Please see abstract for complete disclosure information.
Westhovens R, Rigby W, van der Heijde D, et al. Efficacy and safety of filgotinib for patients with rheumatoid arthritis naïve to methotrexate therapy: FINCH3 primary outcome results. Presented at: European League Against Rheumatism (EULAR) Congress 2019; June 12-15, 2019; Madrid, Spain. Abstract LB0003.