University of California San Diego, La Jolla, CA, USA.
Robarts Clinical Trials, Robarts Research Institute, Western University, London, Ontario, Canada.
Inflamm Bowel Dis. 2021 Jun 15;27(7):994-1007. doi: 10.1093/ibd/izaa236.
Ustekinumab is currently approved globally in Crohn's disease (CD) and psoriatic diseases. Recent phase 3 data demonstrate safety/efficacy in ulcerative colitis (UC). Crohn's disease and UC phase 3 programs had similar study designs, facilitating integrated safety analyses.
Data from 6 ustekinumab phase 2/3 CD and UC studies were pooled, and safety was evaluated through 1 year. Patients received 1 placebo or ustekinumab (generally 130 mg or ~6 mg/kg) intravenous induction, then subcutaneous (90 mg) maintenance every 8/12 weeks. Analyses incorporated all patients who received ≥1 ustekinumab dose. Safety outcomes are presented as percentages of patients (induction) and as number of patients with events per 100 patient-years of follow-up (through 1 year). For key safety events, 95% confidence intervals (CIs) are provided, as appropriate. Hazard ratios with 95% CIs from time-to-event analyses for serious adverse events and serious infections were also performed.
Through 1 year, 2574 patients received ustekinumab (1733 patient-years of follow-up). The number of patients with adverse events per 100 patient-years (placebo 165.99 [95% CI, 155.81-176.67] vs ustekinumab 118.32 [95% CI, 113.25-123.55]), serious AEs (27.50 [95% CI, 23.45-32.04] vs 21.23 [95% CI, 19.12-23.51]), infections (80.31 [95% CI, 73.28-87.84] vs 64.32 [95% CI, 60.60-68.21]), serious infections (5.53 [95% CI, 3.81-7.77] vs 5.02 [95% CI, 4.02-6.19]), and malignancies excluding nonmelanoma skin cancer (0.17 [95% CI, 0.00-0.93] vs 0.40 [95% CI, 0.16-0.83]) were similar between placebo and ustekinumab.
The safety profile of ustekinumab across the pooled inflammatory bowel disease population through 1 year was favorable and generally comparable to placebo. These data are consistent with the established safety profile of ustekinumab across indications.
CLINICALTRIALS.GOV NUMBERS: NCT00265122; NCT00771667; NCT01369329; NCT01369342; NCT01369355; NCT02407236.
乌司奴单抗目前在全球范围内被批准用于克罗恩病（CD）和银屑病疾病。最近的 3 期数据表明其在溃疡性结肠炎（UC）中的安全性/疗效。CD 和 UC 的 3 期计划具有相似的研究设计，这有助于进行综合安全性分析。
对来自 6 项乌司奴单抗 2/3 期 CD 和 UC 研究的数据进行了汇总，并通过 1 年的时间评估了安全性。患者接受 1 次安慰剂或乌司奴单抗（通常为 130mg 或~6mg/kg）静脉诱导，然后每 8/12 周接受 1 次皮下（90mg）维持治疗。分析纳入了接受至少 1 次乌司奴单抗剂量的所有患者。安全性结果以接受治疗的患者百分比（诱导期）和每 100 患者年随访（至 1 年）中发生事件的患者数表示。对于关键安全性事件，提供了 95%置信区间（CI）。还对严重不良事件和严重感染的时间至事件分析进行了风险比及其 95%CI 的计算。
在 1 年期间，2574 名患者接受了乌司奴单抗治疗（1733 患者年的随访）。每 100 患者年发生不良事件的患者数（安慰剂组为 165.99[95%CI，155.81-176.67] vs 乌司奴单抗组为 118.32[95%CI，113.25-123.55]）、严重不良事件（27.50[95%CI，23.45-32.04] vs 21.23[95%CI，19.12-23.51]）、感染（80.31[95%CI，73.28-87.84] vs 64.32[95%CI，60.60-68.21]）、严重感染（5.53[95%CI，3.81-7.77] vs 5.02[95%CI，4.02-6.19]）和非黑色素瘤皮肤癌除外的恶性肿瘤（0.17[95%CI，0.00-0.93] vs 0.40[95%CI，0.16-0.83]）在安慰剂组和乌司奴单抗组之间相似。
在 1 年的时间内，乌司奴单抗在炎症性肠病患者中的安全性特征良好，总体上与安慰剂相当。这些数据与乌司奴单抗在各适应症中的既定安全性特征一致。
NCT00265122；NCT00771667；NCT01369329；NCT01369342；NCT01369355；NCT02407236。
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