Rimegepant for migraine prevention in clinical practice: A multicenter study including patients with prior anti-CGRP monoclonal antibody failure (GEMA project).

BackgroundRimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist approved for both acute and preventive treatment of episodic migraine. Real-world data on its preventive use remain limited, particularly in patients with multiple prior preventive failures. This study evaluated the effectiveness and tolerability of rimegepant in routine clinical practice, focusing on a highly treatment-resistant population.MethodsWe conducted a prospective, multicenter real-world cohort study within the GEMA (GEpants in MigrAine) Project across nine tertiary Headache Units in Spain. Adults initiating rimegepant for migraine prevention were consecutively enrolled and followed for up to 6 months. The primary endpoint was the 3-month change in monthly headache days (MHD). Secondary endpoints included the change in monthly migraine days (MMD), response rates, predictors of response, and tolerability. Baseline characteristics, prior preventive failures, medication overuse, adverse events, and patient-reported outcomes (Headache Impact Test-6 (HIT-6), HADS, and Insomnia Severity Index) were recorded.ResultsIn total, 150 patients completed 3-month follow-up and 64 reached 6 months. The cohort was predominantly female (85.3%), with 70.7% episodic migraine, a median age of 48 years (interquartile range (IQR) = 39-57), and a median of 6 prior preventive failures (IQR = 4-8), reflecting high treatment resistance. At 3 months, median MHD decreased from 12 to 7.5 and MMD from 10 to 6 (p < 0.05), with significant improvement in HIT-6. Overall, 36% and 43% achieved ≥ 50% reduction in MHD and MMD, respectively (≥ 75%: 15% and 20%). Among patients with 6-month data, further reductions were observed (MHD, 6 days; MMD, 5 days), with ≥ 50% response rates increasing to 48% and 58%. Clinical responders showed greater improvements in anxiety and depressive symptoms. Medication overuse, chronic migraine, and prior exposure to anti-CGRP monoclonal antibodies and onabotulinumtoxinA were independent predictors of poorer outcomes, with response declining with increasing prior anti-CGRP exposure, although a relevant proportion still achieved meaningful benefit. Rimegepant was well tolerated, with predominantly mild adverse events (nausea 13%, constipation 8%) and low discontinuation (7% at 3 months), and with nausea being the most frequent cause.ConclusionsRimegepant showed meaningful preventive effectiveness and good tolerability in routine clinical practice, including in highly treatment-resistant patients with prior anti-CGRP monoclonal antibody exposure. The response was influenced by baseline disease burden and prior treatment exposure. These findings suggest that earlier use of rimegepant in the treatment course may be associated with greater clinical benefit.