A Systematic Review and Meta-Analysis of Immune-Related Adverse Events of Anti-PD-1 Drugs in Randomized Controlled Trials

• Published in: Technology in cancer research & treatment 2020, Vol.19, p.1533033820967454-1533033820967454
• Main Authors: Wang, Yukun, Kong, Dejiu, Wang, Chaokun, Chen, Jing, Li, Jing, Liu, Zhiwei, Li, Xinyang, Wang, Ziming, Yao, Ge, Wang, Xinshuai
• Format: Article
• Language: English
• Subjects: Adverse events; Apoptosis; Cell death; Chemotherapy; Clinical trials; Colitis; Drugs; GLP-1 receptor agonists; Hepatitis; Hyperthyroidism; Hypothyroidism; Immunosuppressive agents; Meta-Analysis; Patients; PD-1 protein; Pembrolizumab; Placebos; Pneumonitis; Pruritus
• ISSN: 1533-0346; 1533-0338
• DOI: 10.1177/1533033820967454

Objective: We aimed to evaluate immune-related adverse events occurring in clinical trials of anti-programmed cell death 1 (PD-1) drugs, compared with control treatments, including chemotherapy, targeted drugs, or placebo. Further we compared the occurrence of immune -related events in patients treated with different anti-PD-1 drugs. Data Sources: Randomized controlled trial (RCT) data were sourced from PubMed, Embase, and the Cochrane Central Register of Controlled Trials combined with https://clinicaltrials.gov. Methods: Randomized controlled trial of anti-PD-1 drugs compared with control treatments published between January 1, 1970 and March 1,2019, were searched and data on trial patient characteristics, and adverse events extracted, reviewed, and subjected to meta-analysis. Results: Eighteen Randomized controlled trials were included in our study. The Randomized controlled trials compared nivolumab (n = 12), pembrolizumab (n = 6), with chemotherapy (n = 13), targeted drugs (n = 2), or placebo (n = 3). Compared with the control group, the risk of any immune-related adverse events in patients treated with anti-PD-1 drugs was increased (RR, 2.65; 95% confidence interval, 1.84–3.83; P < 0.00001). Of the immune-related adverse events, the risk rates of pneumonitis (risk ratio, 2.10; 95% CI, 0.85-5.18), colitis (2.96;1.62-5.38), hypophysitis(4.79;1.54-14.89), hypothyroidism(7.87;5.36-11.57), hyperthyroidism (7.03;4.35-11.34), rash (1.58;0.98-2.54), pruritus (2.28; 1.38-3.76), and hepatitis (9.31;2.18-39.85) were increased by anti-PD-1 drugs. Further, the risk of immune-related adverse events was similar for patients treated with pembrolizumab and nivolumab (P = 0.14). Conclusions: In addition to previously reported organ-specific immune-related adverse events, we found that the risk of hyperthyroidism was also increased, in anit-PD-1-treated patients, relative to control treatments. The risk of total immune-related adverse events, was similar for pembrolizumab and nivolumab.