Smolen Josef S, Agarwal Sandeep K, Ilivanova Elena, Xu Xie Lillian, Miao Ye, Zhuang Yanli, Nnane Ivo, Radziszewski Waldemar, Greenspan Andrew, Beutler Anna, Baker Daniel
Medical University of Vienna and Hietzing Hospital, Vienna, Austria.
Baylor College of Medicine, Houston, Texas, USA.
Ann Rheum Dis. 2017 May;76(5):831-839. doi: 10.1136/annrheumdis-2016-209831. Epub 2017 Jan 13.
Interleukin (IL)-12 and IL-23 have been implicated in the pathogenesis of rheumatoid arthritis (RA). The safety and efficacy of ustekinumab, a human monoclonal anti-IL-12/23 p40 antibody, and guselkumab, a human monoclonal anti-IL-23 antibody, were evaluated in adults with active RA despite methotrexate (MTX) therapy.
Patients were randomly assigned (1:1:1:1:1) to receive placebo at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 8 weeks (n=55), ustekinumab 90 mg at weeks 0, 4 and every 12 weeks (n=55), guselkumab 50 mg at weeks 0, 4 and every 8 weeks (n=55), or guselkumab 200 mg at weeks 0, 4 and every 8 weeks (n=54) through week 28; all patients continued a stable dose of MTX (10-25 mg/week). The primary end point was the proportion of patients with at least a 20% improvement in the American College of Rheumatology criteria (ACR 20) at week 28. Safety was monitored through week 48.
At week 28, there were no statistically significant differences in the proportions of patients achieving an ACR 20 response between the combined ustekinumab group (53.6%) or the combined guselkumab group (41.3%) compared with placebo (40.0%) (p=0.101 and p=0.877, respectively). Through week 48, the proportions of patients with at least one adverse event (AE) were comparable among the treatment groups. Infections were the most common type of AE.
Treatment with ustekinumab or guselkumab did not significantly reduce the signs and symptoms of RA. No new safety findings were observed with either treatment.
NCT01645280.
白细胞介素（IL）-12和IL-23与类风湿关节炎（RA）的发病机制有关。对乌司奴单抗（一种人源化抗IL-12/23 p40单克隆抗体）和古塞库单抗（一种人源化抗IL-23单克隆抗体）在尽管接受甲氨蝶呤（MTX）治疗但仍患有活动性RA的成人患者中的安全性和有效性进行了评估。
患者被随机分配（1:1:1:1:1）在第0、4周以及每8周接受安慰剂治疗（n = 55），在第0、4周以及每8周接受90 mg乌司奴单抗治疗（n = 55），在第0、4周以及每12周接受90 mg乌司奴单抗治疗（n = 55），在第0、4周以及每8周接受50 mg古塞库单抗治疗（n = 55），或在第0、4周以及每8周接受200 mg古塞库单抗治疗（n = 54），直至第28周；所有患者继续使用稳定剂量的MTX（10 - 25 mg/周）。主要终点是在第28周时达到美国风湿病学会标准（ACR 20）改善至少20%的患者比例。安全性监测至第48周。
在第28周时，与安慰剂组（40.0%）相比，联合使用乌司奴单抗组（53.6%）或联合使用古塞库单抗组（41.3%）中达到ACR 20反应的患者比例无统计学显著差异（分别为p = 0.101和p = 0.877）。至第48周时，各治疗组中至少发生一次不良事件（AE）的患者比例相当。感染是最常见的AE类型。
使用乌司奴单抗或古塞库单抗治疗并未显著减轻RA的体征和症状。两种治疗均未观察到新的安全性发现。
NCT01645280。
