Ustekinumab as Induction and Maintenance Therapy for Ulcerative Colitis

作者：Bruce E. Sands, William J. Sandborn, Remo Panaccione, Christopher David O'Brien, Hongyan Zhang, Jewel Johanns, Omoniyi J. Adedokun, Katherine Li, Laurent Peyrin‐Biroulet, Gert Van Assche, Silvio Danese, Stephan R. Targan, María T. Abreu, Tadakazu Hisamatsu, Philippe O. Szapary, Colleen W Marano · 发表于：New England Journal of Medicine · 年份：2019 · DOI：10.1056/nejmoa1900750 · 被引用次数：1219 · 研究领域：Inflammatory Bowel Disease、Microscopic Colitis、Immunodeficiency and Autoimmune Disorders

BACKGROUND The efficacy of ustekinumab, an antagonist of the p40 subunit of interleukin-12 and interleukin-23, as induction and maintenance therapy in patients with ulcerative colitis is unknown. METHODS We evaluated ustekinumab as 8-week induction therapy and 44-week maintenance therapy in patients with moderate-to-severe ulcerative colitis. A total of 961 patients were randomly assigned to receive an intravenous induction dose of ustekinumab (either 130 mg [320 patients] or a weight-range–based dose that approximated 6 mg per kilogram of body weight [322]) or placebo (319). Patients who had a response to induction therapy 8 weeks after administration of intravenous ustekinumab were randomly assigned again to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 12 weeks [172 patients] or every 8 weeks [176]) or placebo (175). The primary end point in the induction trial (week 8) and the maintenance trial (week 44) was clinical remission (defined as a total score of ≤2 on the Mayo scale [range, 0 to 12, with higher scores indicating more severe disease] and no subscore >1 [range, 0 to 3] on any of the four Mayo scale components). RESULTS The percentage of patients who had clinical remission at week 8 among patients who received intravenous ustekinumab at a dose of 130 mg (15.6%) or 6 mg per kilogram (15.5%) was significantly higher than that among patients who received placebo (5.3%) (P<0.001 for both comparisons). Among patients who had a respons...