Objective To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments.
Design Systematic review and meta-analysis.
Data sources Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov.
Study selection Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease.
Data extraction Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators.
Results 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain.
Conclusions Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse events may be common.

中文翻译：

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抗 PD-1 和抗 PD-L1 药物的免疫相关不良事件：系统评价和荟萃分析。

目的 总体评估抗程序性细胞死亡 1 (PD-1) 药物的严重器官特异性免疫相关不良事件、与免疫激活相关的一般不良事件以及与肌肉骨骼问题一致的不良事件发生率，并与对照治疗进行比较。
设计系统回顾和荟萃分析。
数据来源Medline、Embase、Cochrane Library、Web of Science 和 Scopus 检索至 2017 年 3 月 16 日，并结合来自 ClinicalTrials.gov 的数据。
研究选择合格的研究包括患有复发或转移性疾病的癌症患者的主要临床试验数据。
数据提取三名独立研究人员从 ClinicalTrials.gov 和已发表的研究中提取了不良事件的数据。三名独立研究人员使用 Cochrane 工具评估偏倚风险。
结果纳入13项相关研究；ClinicalTrials.gov 上提供了八项不良事件的数据。研究将纳武单抗 (n=6)、派姆单抗 (5) 或阿特朱单抗 (2) 与化疗 (11)、靶向药物 (1) 或两者 (1) 进行比较。严重的器官特异性免疫相关不良事件很少见，但与标准治疗相比，甲状腺功能减退症（比值比 7.56，95% 置信区间 4.53 至 12.61）、肺炎（5.37、2.73 至 10.56）、结肠炎（2.88、1.30 至 6.37）的发生率）和垂体炎（3.38，1.02 至 11.08）随着抗 PD-1 药物的增加而增加。在与免疫激活相关的一般不良事件中，只有皮疹发生率（2.34、2.73至10.56）增加。疲劳（32%）和腹泻（19%）的发生率很高，但与对照组相似。与肌肉骨骼问题一致的不良事件的报告不一致；发生率各不相同，但在一些针对关节痛和背痛的研究中，发生率超过 20%。
结论抗PD-1药物引起的器官特异性免疫相关不良事件并不常见，但与对照治疗相比风险增加。与免疫激活相关的一般不良事件大体相似。与肌肉骨骼问题一致的不良事件的报道不一致，但不良事件可能很常见。