Correspondence to Professor G R Burmester, Department of Rheumatology and Clinical Immunology, Charité - University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Ann Rheum Dis. 2013 Apr;72(4):517-24. doi: 10.1136/annrheumdis-2011-201244. Epub 2012 May 5.
As long-term treatment with antitumour necrosis factor (TNF) drugs becomes accepted practice, the risk assessment requires an understanding of anti-TNF long-term safety. Registry safety data in rheumatoid arthritis (RA) are available, but these patients may not be monitored as closely as patients in a clinical trial. Cross-indication safety reviews of available anti-TNF agents are limited.
To analyse the long-term safety of adalimumab treatment.
This analysis included 23 458 patients exposed to adalimumab in 71 global clinical trials in RA, juvenile idiopathic arthritis, ankylosing spondylitis (AS), psoriatic arthritis, psoriasis (Ps) and Crohn's disease (CD). Events per 100 patient-years were calculated using events reported after the first dose through 70 days after the last dose. Standardised incidence rates for malignancies were calculated using a National Cancer Institute database. Standardised death rates were calculated using WHO data.
The most frequently reported serious adverse events across indications were infections with greatest incidence in RA and CD trials. Overall malignancy rates for adalimumab-treated patients were as expected for the general population; the incidence of lymphoma was increased in patients with RA, but within the range expected in RA without anti-TNF therapy; non-melanoma skin cancer incidence was raised in RA, Ps and CD. In all indications, death rates were lower than, or equivalent to, those expected in the general population.
Analysis of adverse events of interest through nearly 12 years of adalimumab exposure in clinical trials across indications demonstrated individual differences in rates by disease populations, no new safety signals and a safety profile consistent with known information about the anti-TNF class.
随着长期使用抗肿瘤坏死因子（TNF）药物成为常规治疗方法，风险评估需要了解抗 TNF 的长期安全性。类风湿关节炎（RA）的注册安全性数据已经可用，但这些患者的监测可能不如临床试验中的患者密切。已上市的抗 TNF 药物的交叉适应证安全性评估有限。
分析阿达木单抗治疗的长期安全性。
这项分析纳入了 71 项 RA、幼年特发性关节炎、强直性脊柱炎（AS）、银屑病关节炎、银屑病（Ps）和克罗恩病（CD）的全球临床试验中接受阿达木单抗治疗的 23458 例患者。通过首剂后至末次剂量后 70 天报告的事件计算每 100 患者-年的事件数。使用国家癌症研究所数据库计算恶性肿瘤的标准化发病率。使用世界卫生组织（WHO）的数据计算标准化死亡率。
在不同适应证中最常报告的严重不良事件是感染，RA 和 CD 试验中发生率最高。阿达木单抗治疗患者的总体恶性肿瘤发生率与一般人群一致；RA 患者的淋巴瘤发生率增加，但在无抗 TNF 治疗的 RA 中处于预期范围内；RA、Ps 和 CD 患者的非黑素瘤皮肤癌发生率升高。在所有适应证中，死亡率均低于或与一般人群预期值相当。
通过在临床试验中对不同适应证中阿达木单抗近 12 年的暴露进行不良事件分析，显示了疾病人群之间发生率的个体差异，没有新的安全性信号，且安全性特征与已知的抗 TNF 类药物信息一致。
