Adalimumab Safety in Global Clinical Trials of Patients with Crohn's Disease
Adalimumab Safety in Global Clinical Trials of Patients with Crohn's Disease
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DOI：
10.1002/ibd.20956
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发表时间：
2009-09-01
影响因子：
4.9
通讯作者：
Cardoso, Alexandra T.
中科院分区：
文献类型：
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作者：
Colombel, Jean-Frederic;Sandborn, William J.;Cardoso, Alexandra T.
背景：阿达木单抗，一种全人源抗肿瘤坏死因子（抗TNF）单克隆抗体。被批准用于治疗成人克罗恩病（CD）。我们在CD患者的全球临床试验中评价了阿达木单抗的总体安全性特征。参加这些试验的患者，包括随机诱导和维持试验、IIIb期试验和开放标签扩展研究。中度至重度活动性CD，并定期评估其安全性。方法：每100例阿达木单抗暴露患者年评估不良事件发生率。使用人群匹配数据计算标准化死亡率和标准化发病率（恶性肿瘤）。截至2008年4月15日，3160例CID患者在临床试验中接受了阿达木单抗治疗。结果：严重感染是CD试验中最常报告的严重不良事件，脓肿（腹腔内和胃肠道相关）是最常见的严重感染。CD试验中报告的恶性肿瘤、淋巴瘤、结核性感染（包括结核病）、脱髓鞘疾病和狼疮样疾病的发生率较低。阿达木单抗治疗CD患者的标准化死亡率为0.44（95%置信区间[CI]，0.12-1.12）。低于最近CD患者荟萃分析中报告的1.52（95%CI，1.32-1.74）。结论：阿达木单抗在CD患者中的安全性特征与CD人群中其他TNF拮抗剂相似，不良事件发生率与其他批准的阿达木单抗适应症相当，临床观察时间>10年。未发现新的安全性信号。
Background: Adalimumab, a fully human anti-tumor necrosis factor (anti-TNF) monoclonal antibody. is approved for the treatment of Crohn's disease (CD) in adults. We evaluated the overall safety profile of adalimumab in global clinical trials ill patients with CD. Patients who participated in these trials, which included randomized induction and maintenance trials, Phase IIIb trials, and open-label extension Studies. had moderately to severely active CD and were evaluated for safety at regular intervals.Methods: Rates of adverse events of interest were assessed per 100-patient-years of adalimumab exposure. Standardized mortality rates and standardized incidence rates (for malignancies) were calculated using population-matched data. As of April 15, 2008, 3160 patients with CID had been treated with adalimumab in clinical trials. representing 3401.9 patient-years of adalimumab exposure.Results: Serious infection was the most frequently reported serious adverse event of interest in the CD trials abscess (intraabdominal and gastrointestinal related) was the most common serious infection. Low incidences of malignancies, lymphomas, Opportunistic infections (including tuberculosis), demyelinating disorders, and lupus-like disorders were reported in the CD trials. The standardized mortality rate for adalimumab-treated patients with CD, 0.44 ( 95% confidence interval [CI], 0.12-1.12). is less than the rate of 1.52 (95% Cl, 1.32-1.74) reported in a recent meta-analysis of patients with CD.Conclusions: The safety profile of adalimumab in patients with CD was similar to that of other TNF antagonists in CD populations, and the rates of adverse events were comparable to other approved indications for adalimumab spanning >10 years of clinical observation. No new safety signals were identified.