乌司奴单抗在炎症性肠病中的安全性：克罗恩病 5 年和溃疡性结肠炎 4 年汇总安全性分析。
Safety of Ustekinumab in Inflammatory Bowel Disease: Pooled Safety Analysis Through 5 Years in Crohn's Disease and 4 Years in Ulcerative Colitis.
机构信息
APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland.
Western University and Alimentiv Inc., London, ON, Canada.
出版信息
J Crohns Colitis. 2024 Aug 6;18(7):1091-1101. doi: 10.1093/ecco-jcc/jjae013.
BACKGROUND AND AIMS
Previously published long-term safety data reported a favourable ustekinumab safety profile for the treatment of inflammatory bowel disease [IBD]. We present the final cumulative safety data from pooled ustekinumab IBD phase 2/3 clinical studies through 5 years in Crohn's disease [CD] and 4 years in ulcerative colitis [UC].
METHODS
In phase 3 studies, patients received a single intravenous placebo or ustekinumab [130 mg or ~6 mg/kg] induction dose followed by subcutaneous maintenance doses of placebo or ustekinumab [90 mg q8w or q12w]. Analyses included all patients who received one dose of study treatment and included patients who were biologic-naïve and patients with a history of biologic failure. Safety outcomes are summarized and presented using number of events per 100 patient-years of follow-up and corresponding 95% confidence intervals.
RESULTS
In this final pooled safety analysis, 2575 patients were treated with ustekinumab with 4826 patient-years of follow-up. Rates of key safety events, including major adverse cardiac events and malignancies, were similar between placebo and ustekinumab or not higher for ustekinumab. Opportunistic infections, including tuberculosis, and malignancies were reported infrequently. Rates of key safety events in the IBD group were no higher in the ustekinumab group than in the placebo group for both patients who were biologic-naïve or who had a history of biologic failure. No lymphomas or cases of posterior reversible encephalopathy syndrome [formerly known as reversible posterior leukoencephalopathy syndrome] were reported.
CONCLUSION
The final cumulative ustekinumab safety data through 5 years in CD and 4 years in UC demonstrated favourable safety compared to placebo and continue to support the well-established safety profile across all approved indications.
CLINICAL TRIALS.GOV NUMBERS: NCT00265122, NCT00771667, NCT01369329, NCT01369342, NCT01369355, NCT02407236.
背景与目的
先前发表的长期安全性数据报告称，乌司奴单抗治疗炎症性肠病（IBD）具有良好的安全性。我们展示了克罗恩病（CD）5 年和溃疡性结肠炎（UC）4 年的乌司奴单抗 IBD 2/3 期临床研究中汇总的最终累积安全性数据。
方法
在 3 期研究中，患者接受单次静脉注射安慰剂或乌司奴单抗（130mg 或~6mg/kg）诱导剂量，然后皮下给予安慰剂或乌司奴单抗（90mg 每 8 周或每 12 周）维持剂量。分析包括接受了一剂研究治疗的所有患者，包括生物初治患者和生物治疗失败的患者。安全性结果采用每 100 患者-年随访的事件数以及相应的 95%置信区间进行总结和呈现。
结果
在这项最终的汇总安全性分析中，2575 例患者接受了乌司奴单抗治疗，随访时间为 4826 患者-年。关键安全性事件（包括重大不良心脏事件和恶性肿瘤）的发生率在安慰剂组和乌司奴单抗组之间相似，或乌司奴单抗组并不更高。机会性感染（包括结核病）和恶性肿瘤的报告频率较低。在生物初治或生物治疗失败的患者中，乌司奴单抗组的关键安全性事件发生率在 IBD 组中并不高于安慰剂组。未报告淋巴瘤或后部可逆性脑病综合征（以前称为可逆性后部白质脑病综合征）病例。
结论
在 CD 中经过 5 年和 UC 中经过 4 年的最终累积乌司奴单抗安全性数据显示与安慰剂相比具有良好的安全性，并继续支持在所有批准的适应症中确立的良好安全性概况。
临床试验.gov 编号：NCT00265122、NCT00771667、NCT01369329、NCT01369342、NCT01369355、NCT02407236。
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