PD-L1 has a stronger effect on increasing headache risk than PD-1: a systematic review and meta-analysis

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PURPOSE: This meta-analysis aimed to clarify the risk of headaches caused by programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors. METHOD: Relevant clinical trials were screened using PubMed. The risk of headache associated with PD-1 or PD-L1 inhibitors was calculated using the mirror principle and PRISMA guidelines. RESULTS: A total of 33 clinical trials were screened for this comprehensive meta-analysis, yielding nine mirror-pairing groups. The risk of headache with PD-1 or PD-L1 inhibitors was significantly higher than that with placebo (OR = 1.48, 95% CI: [1.06, 2.06], Z = 2.33, P = 0.02) and similar to that with chemotherapy drugs (OR = 1.06, 95% CI: [0.84, 1.34], Z = 0.49, P = 0.62). When PD-1 or PD-L1 inhibitors are combined with other immune-related drugs, the risk of headaches increases to varying degrees. However, when combined with chemotherapy, this risk did not increase significantly (OR = 1.02, 95% CI: [0.78, 1.32], Z = 0.11, P = 0.91). Compared with PD-1, PD-L1 inhibitors were associated with a higher headache risk (OR = 1.39, 95% CI: [0.64, 2.12], Z = 1.51, P = 0.13). CONCLUSION: PD-L1 has a stronger effect on increasing headache risk than PD-1. Similar to the comparison of PD-1 or PD-L1 versus chemotherapy, PD-1 or PD-L1 plus chemotherapy did not significantly increase headache risk.

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