To evaluate the frequency of status epilepticus (SE) in epilepsy patients on calcitonin gene-related peptide (CGRP) inhibitors compared to those not on these treatments.

CGRP inhibitors play a key role in pain modulation and neuroinflammation, which is a well-known contributor to epileptogenesis and SE. We present first evidence comparing frequency of intractable and non-intractable SE in epilepsy patients on CGRP inhibitors.

A retrospective cohort study was conducted across 130 healthcare organizations worldwide using the TriNetX database. We identified patients with a history of epilepsy before May 18, 2018. Cohorts were balanced for variables such as age, sex, race, anticonvulsants, and conventional analgesics including triptans using propensity score matching. Our primary outcome was defined as an occurrence of SE on the TriNetX database on/or before May 2024. Odds ratio, risk ratio, risk difference with 95% CI and t-test were performed.  

We identified 17,569 and 1,640,134 epilepsy patients on and not on CGRP inhibitors respectively. Following matching, we identified 11,820 epilepsy patients on CGRP inhibitors and 12,605 epilepsy patients not on CGRP inhibitors, with a total of 370 (3.13%) and 705 (5.59%) patients, respectively, diagnosed with SE. Risk difference between both arms was -2.46%, p < .0001, 95% CI [-2.97%, -1.95%], risk ratio was calculated at 0.56, 95% CI [0.50, 0.63] with an odds ratio of 0.54, 95% CI [0.48, 0.62] showing a significant reduction in occurrence and likelihood of SE among patients on CGRP inhibitors. Hospital visits due to SE were significantly less, t = -5.37, df = 24, 423, p < .0001 in epilepsy patients on CGRP inhibitors.

CGRP inhibitors are associated with a reduced frequency of hospital visits due to SE and should be considered a drug of choice among patients with migraine and epilepsy as comrbidities. RCTs are encouraged to look more closely into this potential treatment option.