Baricitinib versus Placebo or Adalimumab in Rheumatoid Arthritis

作者：Peter Charles Taylor, Edward Clark Keystone, Désirée M F M van der Heijde, Michael E. Weinblatt, Liliana Morales, Jaime Reyes Gonzaga, S. S. Yаkushin, Taeko Ishii, Kahaku Emoto, Scott D. Beattie, Vipin Arora, Carol L. Gaich, Terence P. Rooney, Douglas E. Schlichting, William L. Macias, Stephanie de Bono, Yoshiya Tanaka · 发表于：New England Journal of Medicine · 年份：2017 · DOI：10.1056/nejmoa1608345 · 被引用次数：977 · 研究领域：Rheumatoid Arthritis Research and Therapies、Spondyloarthritis Studies and Treatments、Autoimmune and Inflammatory Disorders Research

BACKGROUND: Baricitinib is an oral, reversible inhibitor of the Janus kinases JAK1 and JAK2 that may have therapeutic value in patients with rheumatoid arthritis. METHODS: We conducted a 52-week, phase 3, double-blind, placebo- and active-controlled trial in which 1307 patients with active rheumatoid arthritis who were receiving background therapy with methotrexate were randomly assigned to one of three regimens in a 3:3:2 ratio: placebo (switched to baricitinib after 24 weeks), 4 mg of baricitinib once daily, or 40 mg of adalimumab (an anti-tumor necrosis factor α monoclonal antibody) every other week. End-point measures evaluated after adjustment for multiplicity included 20% improvement according to the criteria of the American College of Rheumatology (ACR20 response) (the primary end point), the Disease Activity Score for 28 joints (DAS28), the Health Assessment Questionnaire-Disability Index, and the Simplified Disease Activity Index at week 12, as well as radiographic progression of joint damage as measured by the van der Heijde modification of the total Sharp score (mTSS) (range, 0 to 448, with higher scores indicating greater structural joint damage) at week 24. RESULTS: More patients had an ACR20 response at week 12 with baricitinib than with placebo (primary end point, 70% vs. 40%, P<0.001). All major secondary objectives were met, including inhibition of radiographic progression of joint damage, according to the mTSS at week 24 with baricitinib versus placebo (mean...