Oregon Health & Science University, Portland.
University of California, San Francisco.
Arthritis Rheumatol. 2019 Feb;71(2):258-270. doi: 10.1002/art.40728. Epub 2018 Dec 29.
To evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo-controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti-tumor necrosis factor [anti-TNF]-naive patients and patients with inadequate response or intolerance to anti-TNF, respectively); study 3 patients had nonradiographic axial SpA.
In all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo-treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3.
For study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies.
In these 3 placebo-controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications.
评估乌司奴单抗在 3 项随机、安慰剂对照的轴性脊柱关节炎（SpA）患者研究中的疗效和安全性。研究 1 和 2 纳入了影像学轴性 SpA（抗肿瘤坏死因子[anti-TNF]初治患者和抗 TNF 治疗应答不足或不耐受的患者）；研究 3 纳入了非影像学轴性 SpA 患者。
在所有 3 项研究中，患者按 1:1:1 的比例随机分配接受皮下注射乌司奴单抗 45 mg 或 90 mg 或安慰剂，最多 24 周，之后安慰剂治疗的患者再随机分配接受乌司奴单抗 45 mg 或 90 mg。研究 1 和 2 的主要终点是达到强直性脊柱炎评估协会（ASAS）40%疾病活动改善标准的患者比例（达到 ASAS40 应答）。研究 3 的主要终点是达到 ASAS20 应答的患者比例。还评估了其他疾病活动和安全性指标。研究 1 的 24 周周分析是预先计划的，以确定研究 2 和 3 的继续进行。
对于研究 1，主要和主要次要终点均未达到，该研究被终止。因此，在研究 2 和 3 完全入组之前，它们被提前终止。对于所有 3 项研究，乌司奴单抗组在关键疗效终点上均未显示出与安慰剂相比有临床意义的改善。乌司奴单抗组发生不良事件的患者比例与之前的研究一致。
在这 3 项安慰剂对照试验中，乌司奴单抗在治疗轴性 SpA 方面的疗效未得到证实。安全性与其他适应证的研究一致。
