Could calcitonin gene‐related peptide inhibitors prevent status epilepticus?

Abstract

Calcitonin gene‐related peptide (CGRP) inhibitors modulate pain and neuroinflammation, a recognized contributor to epileptogenesis and status epilepticus (SE). We examined the association between CGRP inhibitor use and SE hospitalization in epilepsy patients with comorbid migraine. Using TriNetX (130 healthcare organizations), we identified patients with epilepsy from May 2018 through May 2026, and propensity‐matched cohorts for age, sex, race, anti‐seizure medications (ASMs), migraine diagnosis, migraine treatments, and cognitive impairment. The primary outcome was SE occurrence. Following matching, 17 738 patients were on CGRP inhibitors and 18 594 were not. SE occurred in 427 (2.41%) and 860 (4.63%) patients, respectively. Mean age (±SD) was 48.4 ± 14.9 vs 48.9 ± 17.0 years. Risk difference was −2.2% (95% confidence interval [CI]: −2.6% to −1.8%, p  < .001), risk ratio 0.52 (95% CI: 0.46–0.58), and odds ratio 0.51 (95% CI: 0.45–0.57). SE‐related hospital visits were significantly fewer in the CGRP inhibitor group ( t  = −6.60, p  < .001). CGRP inhibitor use was associated with reduced SE occurrence and hospitalization, supporting further investigation in patients with comorbid migraine and epilepsy.