Risk of pituitary immune-related adverse events caused by immune checkpoint inhibitors:a systematic review and meta-analysis.

Immune checkpoint inhibitors (ICIs) induced hypophysitis is one of the common endocrine immune-related adverse events (irAEs). Our goal is to evaluate the risk of pituitary irAEs caused by ICIs. The relevant literatures were retrieved from PubMed, Embase and Cochrane Library from inception to October 31, 2024.References were screened according to inclusion and exclusion criteria and study data were extracted. Meta-analysis was performed using Revman5.3 and Stata18.0 software. A total of 21 prospective single-arm trials and 17 randomized controlled trials (RCTs) were included. In single-arm trials, the incidence of hypophysitis (4.00%) and hypopituitarism (3.84%) caused by CTLA-4 was the highest in monotherapy, and the incidence of hypophysitis caused by PD-1 plus CTLA-4 was the highest in ICIs combination therapy (9.36%). In RCTs, the risk of pituitary irAEs caused by ICIs was higher than that of the control group (RR=10.09, 95%CI 6.90-14.75). Compared with monotherapy, ICIs combination therapy has a higher risk of pituitary irAEs (RR=5.42, 95%CI 3.36-8.73). In monotherapy, CTLA-4 caused the highest incidence of hypophysitis and hypopituitarism, reaching 16.17% and 1.75% respectively. Furthermore, the severity of adverse pituitary irAEs caused by CTLA-4 was also the highest (in single-arm trials 5.12%, in RCTs 16.35%). The results showed that ICIs is associated with a significantly higher risk of pituitary irAEs, and ICIs combination may further increase the risk. In monotherapy, CTLA-4 caused the highest incidence and severity of pituitary irAEs, while PD-L1 caused the lowest. In combination therapy, PD-1 combined with CTLA-4 resulted in a higher incidence of hypophysitis.