Filgotinib in combination with methotrexate or as monotherapy versus methotrexate monotherapy in patients with active rheumatoid arthritis and limited or no prior exposure to methotrexate: the phase 3, randomised controlled FINCH 3 trial.

Abstract

OBJECTIVES:

To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.

METHODS:

This 52-week, phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.

RESULTS:

The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.

CONCLUSIONS:

FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.

• Authors: René Westhovens, William F C Rigby, Désirée van der Heijde, Daniel W T Ching, William Stohl, Jonathan Kay, Arvind Chopra, Beatrix Bartok, Franziska Matzkies, Zhaoyu Yin, Ying Guo, Chantal Tasset, John S Sundy, Angelika Jahreis, Neelufar Mozaffarian, Osvaldo Daniel Messina, Robert Bm Landewé, Tatsuya Atsumi, Gerd R Burmester
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 80 Issue 6 Pg. 727-738 (06 2021) ISSN: 1468-2060 [Electronic] England
• PMID: 33452004 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Antirheumatic Agents
• GLPG0634
• Pyridines
• Triazoles
• Methotrexate

Topics

• Animals
• Antirheumatic Agents (adverse effects)
• Arthritis, Rheumatoid (diagnosis)
• Double-Blind Method
• Drug Therapy, Combination
• Finches
• Humans
• Methotrexate (therapeutic use)
• Pyridines
• Treatment Outcome
• Triazoles