Glaucoma Risk Associated With Calcitonin Gene-Related Peptide Inhibitor Use in Migraine: A Multinational Cohort Study.

Abstract

Migraine has been linked to an increased risk of glaucoma, and our study aims to assess the temporal association between calcitonin gene-related peptide inhibitors (CGRPi) and the risks of glaucoma in individuals with migraine. This multinational retrospective cohort study included adults diagnosed with migraine who received migraine preventive medications in 2018-2024. Participants were categorized into the CGRPi group (erenumab, fremanezumab, galcanezumab, eptinezumab, atogepant, or rimegepant) and non-CGRPi group (valproate, topiramate, flunarizine, candesartan, lisinopril, metoprolol, propranolol, nadolol, amitriptyline, and venlafaxine). Crossovers were not allowed, and the non-CGRPi group included only individuals who never used CGRPi. The CGRPi and non-CGRPi groups were propensity score matched in a 1:1 ratio and were followed for up to 3 years to monitor the occurrence of incident glaucoma. The Cox proportional hazards model was used to compare the risk of glaucoma between CGRPi and non-CGRPi users, with results reported as hazard ratios (HRs) and 95% CIs. A total of 73,644 individuals were included in the final analysis. Compared with non-CGRPi users, CGRPi users experience a lower risk of glaucoma development (HR 0.75; 95% CI 0.61-0.92) within 3 years since its first prescription. Individuals using CGRPi also exhibit a reduced risk of glaucoma compared with those using topiramate (HR 0.73; 95% CI 0.59-0.90), valproate (HR 0.54; 95% CI 0.35-0.83), propranolol (HR 0.76; 95% CI 0.59-0.98), metoprolol (HR 0.76; 95% CI 0.59-0.98), lisinopril (HR 0.49; 95% CI 0.38-0.62), amitriptyline (HR 0.69; 95% CI 0.54-0.89), and venlafaxine (HR 0.68; 95% CI 0.50-0.91). In the analysis that further classified participants based on the specific CGRPi used, only users of monoclonal antibody CGRPi show a reduced risk of glaucoma compared with non-CGRPi users (HR 0.77; 95% CI 0.61-0.98). The reduced risk of glaucoma associated with CGRPi is also observed in older adults, women, and those with chronic migraine or migraine without aura. Among adults with migraine receiving preventive treatment, systemic use of CGRPi, particularly monoclonal antibody CGRPi, is associated with a reduced risk of glaucoma compared with the use of other migraine preventive medications. This is a Class II study demonstrating that CGRPi users with migraine have a lower risk of incident glaucoma when compared with non-CGRPi users with migraine.