Immune Checkpoint Inhibitors in Cancer Patients with Pre-existing Autoimmune Disease: Comparative Safety and Efficacy in a Registered Systematic Review.
BACKGROUND This study aimed to compare the safety and efficacy of immune checkpoint inhibitors (ICIs) in patients with and without pre-existing autoimmune disease (AID). METHODS We conducted a registered systematic review with a restricted meta-analysis. PubMed, EMBASE, and the Cochrane Library were searched for publications from January 2015 through December 2025; a PubMed rerun and source-verification update were completed in May 2026. The prespecified outcomes included any-grade immune-related adverse events (irAEs), grade ≥3 irAEs, autoimmune disease flares, treatment discontinuation, and efficacy outcomes. Comparative studies reporting outcomes for patients with and without pre-existing AID were included. Directly poolable patient-level event data were analyzed separately from adjusted-only, organ-specific, phenotype-specific, treatment-line, and AID-only evidence. RESULTS A total of 25 studies were included, five contributed to the any-grade irAE meta-analysis and four to the grade ≥3 irAE analysis. Pre-existing AID was associated with a higher risk of any-grade irAEs (risk ratio [RR] 1.34, 95% confidence interval [CI] 1.13-1.60), whereas the evidence for grade ≥3 irAEs remained inconclusive (RR 0.99, 95% CI 0.66-1.47). Available data were insufficient to determine whether pre-existing AID modified antitumour efficacy. CONCLUSION Pre-existing AID was associated with an increased risk of any-grade irAEs, whereas comparative evidence for severe toxicity and efficacy remained uncertain. Treatment with ICIs should be individualized instead of withheld solely because of stable pre-existing AID.