Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases
Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases
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DOI：
10.1136/ard.2008.102103
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发表时间：
2009-12-01
影响因子：
27.4
通讯作者：
Pangan, A. L.
中科院分区：
文献类型：
--
作者：
Burmester, G. R.;Mease, P.;Pangan, A. L.
目的：肿瘤坏死因子拮抗剂的临床试验提出了关于某些严重不良事件（SAE）潜在风险的问题。评估阿达木单抗在类风湿性关节炎（RA）中随时间推移的安全性以及在其他五种免疫介导的炎症性疾病中的安全性，并将阿达木单抗的恶性肿瘤和死亡率与普通人群的数据进行比较。该分析纳入了在36项全球临床试验中暴露于阿达木单抗的19041例患者，这些临床试验涉及RA、银屑病关节炎（PsA）、强直性脊柱炎（AS）、克罗恩病（CD），银屑病和幼年特发性关节炎（JIA）至2007年4月15日。使用首次给药后至末次给药后70天报告的SAE计算每100患者-年的事件。使用国家和州特定数据库计算恶性肿瘤的标准化发病率。标准化死亡率（SMR）计算每种疾病使用的数据从世界卫生组织。结果：在RA的利益SAE的累积率一直保持稳定，随着时间的推移。PsA、AS、CD、银屑病和JIA的关注SAE发生率与RA相似或低于RA。阿达木单抗治疗患者的总体恶性肿瘤发生率与一般人群的预期结果一致。SMR在所有六种疾病表明，没有更多的死亡发生阿达木单抗比预期在一般population.Conclusions：根据10年的临床试验经验，在六种疾病，本安全性报告和阿达木单抗在这些疾病的疗效提供了基础，更好地了解其效益-风险特征。
Objectives: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population.Methods: This analysis included 19 041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic arthritis (PsA), ankylosing spondylitis (AS), Crohn's disease (CD), psoriasis and juvenile idiopathic arthritis (JIA) to 15 April 2007. Events per 100 patient-years were calculated using SAE reported after the first dose to 70 days after the last dose. Standardised incidence rates were calculated for malignancies using national and state-specific databases. Standardised mortality rates (SMR) were calculated for each disease using data from the World Health Organization.Results: Cumulative rates of SAE of interest in RA have remained stable over time. Rates of SAE of interest for PsA, AS, CD, psoriasis and JIA were similar to or lower than rates for RA. Overall malignancy rates for adalimumab-treated patients were as expected for the general population. SMR across all six diseases indicated that no more deaths occurred with adalimumab than expected in the general population.Conclusions: Based on 10 years of clinical trial experience across six diseases, this safety report and the established efficacy of adalimumab in these diseases provide the foundation for a better understanding of its benefit-risk profile.