Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial

• Published in: Annals of the rheumatic diseases Vol. 80; no. 7; pp. 848 - 858
• Main Authors: Combe, Bernard, Kivitz, Alan, Tanaka, Yoshiya, van der Heijde, Désirée, Simon, J Abraham, Baraf, Herbert S B, Kumar, Uma, Matzkies, Franziska, Bartok, Beatrix, Ye, Lei, Guo, Ying, Tasset, Chantal, Sundy, John S, Jahreis, Angelika, Genovese, Mark C, Mozaffarian, Neelufar, Landewé, Robert B M, Bae, Sang-Cheol, Keystone, Edward C, Nash, Peter
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and European League Against Rheumatism 01.07.2021; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adalimumab; Adult; Adverse events; Aged; Antirheumatic Agents; arthritis; Arthritis, Rheumatoid; C-reactive protein; Clinical outcomes; Clinical trials; Cytokines; Double-Blind Method; Drug dosages; Drug Therapy, Combination; Enzyme inhibitors; Female; Human health and pathology; Humans; Hypotheses; Immunology; Immunotherapy; Janus kinase; Joint diseases; Laboratories; Life Sciences; Male; Methotrexate; Middle Aged; Monoclonal antibodies; Patients; Placebos; Pyridines; Response rates; rheumatoid; Rheumatoid Arthritis; Rheumatology; Rhumatology and musculoskeletal system; Statistical analysis; therapeutics; Thromboembolism; TNF inhibitors; Triazoles; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Tumors; therapeutics; arthritis; antirheumatic agents; rheumatoid
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2020-219214

ObjectiveTo evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX).MethodsThis 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities.ResultsThe proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms.ConclusionsFilgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab.Trial registration numberNCT02889796.