PT  - JOURNAL ARTICLE
AU  - Combe, Bernard
AU  - Kivitz, Alan
AU  - Tanaka, Yoshiya
AU  - van der Heijde, Désirée
AU  - Simon, J Abraham
AU  - Baraf, Herbert S B
AU  - Kumar, Uma
AU  - Matzkies, Franziska
AU  - Bartok, Beatrix
AU  - Ye, Lei
AU  - Guo, Ying
AU  - Tasset, Chantal
AU  - Sundy, John S
AU  - Jahreis, Angelika
AU  - Genovese, Mark C
AU  - Mozaffarian, Neelufar
AU  - Landewé, Robert B M
AU  - Bae, Sang-Cheol
AU  - Keystone, Edward C
AU  - Nash, Peter
TI  - Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial
AID  - 10.1136/annrheumdis-2020-219214
DP  - 2021 Jul 01
TA  - Annals of the Rheumatic Diseases
PG  - 848--858
VI  - 80
IP  - 7
4099  - http://ard.bmj.com/content/80/7/848.short
4100  - http://ard.bmj.com/content/80/7/848.full
SO  - Ann Rheum Dis2021 Jul 01; 80
AB  - Objective To 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).Methods This 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.Results The 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.Conclusions Filgotinib 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 number NCT02889796.Data are available upon reasonable request. Anonymised individual patient data will be shared upon request for research purposes dependent upon the nature of the request, the merit of the proposed research, the availability of the data and the intended use. The full data sharing policy for Gilead Sciences can be found at https://www.gilead.com/about/ethics-and-code-of-conduct/policies.