Aim To determine if checkpoint inhibitors (CPIs) confer an increased risk of non-infectious uveitis or myasthenia gravis (MG) compared to patients on non-checkpoint inhibitor (N-CPI) chemotherapy.
Methods A retrospective cohort study was performed comparing patients in a large commercial and Medicare advantage database exposed to CPI compared to N-CPI. All patients who initiated a CPI (ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, cemiplimab and durvalumab) were eligible. Date of earliest CPI in the exposure group and N-CPI chemotherapy in the comparator group was considered the index date. Exclusion occurred in both cohorts for any history of uveitis or MG diagnosis and having <1 year in the insurance plan prior to the index date, and <6 months in plan following the index date. Every exposed patient was matched up to 1:10 based on demographics and index year to patients on N-CPI chemotherapy. Multivariate Cox proportional hazards regression modelling was performed.
Results For evaluation of incidence of non-infectious uveitis, 26 (0.3%) of 8678 patients on CPI and 123 (0.2%) of 76 153 N-CPI comparators were found to have non-infectious uveitis. After multivariate analysis, CPIs showed an increased hazard for uveitis compared to N-CPI (HR=2.09; 95% CI 1.36 to 3.22, p=0.001). For the MG analysis, 11 (0.1%) of 9210 patients developed MG in the CPI group and 36 (0.04%) of 80 620 comparators. The CPI cohort had a higher hazard of developing MG (HR=2.60; 95% CI 1.34 to 5.07, p=0.005) compared to controls in multivariate analysis.
Conclusions Exposure to CPI confers a higher risk for non-infectious uveitis and MG compared to N-CPI chemotherapy.
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Contributors TX initiated the study idea, designed the study, drafted and revised the paper; AJB revised the paper; BM designed the study, collected and analysed data, and revised the paper; BLV designed the study, analysed the data, drafted and revised the paper.
Funding This study was supported by the National Institutes of Health K23 Award (1K23EY025729-01) and University of Pennsylvania Core Grant for Vision Research (2P30EY001583). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Additional funding was provided by Research to Prevent Blindness, Karen & Herbert Lotman Fund for Macular Vision Research Foundation, and the Paul and Evanina Mackall Foundation (no award/grant number). None of the funding organisations had any role in the design or conduction of the study.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Due to contractual agreement, data are not able to disseminated by the authors, however, data are available for purchase from OptumInsight.