METHODS: The difference in risk of immune-associated pneumonitis between PD-1 and PD-L1 inhibitors was assessed by two different meta-analysis methods, the Mirror-pairing and the PRISMA guidelines.
RESULTS: A total of eighty-eight reports were used for meta-analysis, while thirty-two studies were used for the Mirror-pairing. Both PD-1 and PD-L1 inhibitors (used alone or combined with chemotherapy) increased the risk of developing immune-related pneumonitis (P < 0.00001; P < 0.00001). Based on indirect analyses results (subgroup analyses), the risk of PD-L1-induced pneumonitis was weaker than that of PD-1 inhibitors when the control group was chemotherapy (OR = 3.33 vs. 5.43) or placebo (OR = 2.53 vs. 3.19), while no obvious significant differences were found (P = 0.17; P = 0.53). For the Mirror-pairing-based meta-analysis, the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors (OR = 1.46, 95%CI [1.08, 1.98], I2 = 0%, Z = 2.47 (P = 0.01)). However, this difference was not significant, when they were combined with chemotherapy (OR = 1.05, 95%CI [0.68, 1.60], I2 = 38%, Z = 0.21 (P = 0.84)).
CONCLUSIONS: Both PD-1 and PD-L1 inhibitors increased the risk of immune-related pneumonitis, while the risk of PD-1-induced pneumonitis was significantly higher than that of PD-L1 inhibitors.
方法:通过两种不同的荟萃分析方法评估了PD-1和PD-L1抑制剂之间免疫相关性肺炎风险的差异,镜像配对和PRISMA指南。
结果:共有88份报告用于荟萃分析,而32项研究用于镜像配对。PD-1和PD-L1抑制剂(单独使用或与化疗联合使用)都会增加发生免疫相关性肺炎的风险(P<0.00001;P<0.00001)。基于间接分析结果(子组分析),对照组化疗时,PD-L1诱导肺炎的风险弱于PD-1抑制剂(OR=3.33vs.5.43)或安慰剂(OR=2.53vs.3.19),差异无统计学意义(P=0.17;P=0.53)。对于基于镜像配对的荟萃分析,PD-1诱导肺炎的风险显著高于PD-L1抑制剂(OR=1.46,95CI[1.08,1.98],I2=0%,Z=2.47(P=0.01))。然而,这种差异并不显著,联合化疗时(OR=1.05,95CI[0.68,1.60],I2=38%,Z=0.21(P=0.84))。
结论:PD-1和PD-L1抑制剂都会增加免疫相关性肺炎的风险,而PD-1诱导的肺炎风险明显高于PD-L1抑制剂。