Incidence and risk assessment of thyroid dysfunction following immune checkpoint inhibitor therapy: a systematic review and meta-analysis.

[BACKGROUND] Immune checkpoint inhibitors (ICIs) have significantly enhanced the clinical outcomes for cancer patients. Nevertheless, they may be associated with the occurrence of ICI-associated thyroid dysfunction (ICI-TD). This study aimed to assess the risk of thyroid dysfunction in patients receiving ICI therapy.

[METHODS] We systematically searched the PubMed, Embase, and Cochrane Library databases for phase II/III randomized controlled trials (RCTs) evaluating the use of ICIs in malignant tumors. The statistical analyses were conducted using Stata (version 17), and the risk of bias was assessed using Review Manager (version 5.4).

[RESULTS] In total, 40 RCTs encompassing 12,376 patients were included. A higher relative risk (RR) of all-grade hyperthyroidism (RR = 9.91, 95% CI: 5.80-16.94; P < 0.01) was observed compared to hypothyroidism (RR = 7.70, 95% CI: 4.88-12.17; P < 0.01). Subgroup analyses indicated that combination ICI therapy was associated with a significantly higher incidence of ICI-TD than monotherapy. Among combination regimens, the PD-L1 combined with CTLA-4 group showed the highest risk of hypothyroidism (RR = 20.87, 95% CI: 5.07-85.81; P < 0.001), whereas the PD-1 combined with CTLA-4 group exhibited the highest risk of hyperthyroidism (RR = 17.34, 95% CI: 3.88-77.45; P < 0.001).

[CONCLUSION] ICI-associated hyperthyroidism was found to occur more frequently than hypothyroidism. Moreover, combination therapies significantly increased the incidence of ICI-TD.