Delayed urticaria during treatment with anti-CGRP monoclonal antibodies in migraine.

Objective To characterize clinical presentation and management of urticaria associated with calcitonin gene-related peptide (CGRP) -targeting monoclonal antibodies (mAbs) for migraine prophylaxis.Background CGRP-targeting mAbs are effective in migraine prophylaxis, but have been associated with hypersensitivity reactions, including urticaria. The underlying mechanisms, risk factors, and therapeutic consequences of these anti-CGRP mAb-related hypersensitivity reactions remain poorly understood.Methods We performed a retrospective case series with descriptive analysis on five patients who developed urticaria after anti-CGRP mAb administration. Timing of reactions, history of urticaria, re-exposure strategies including premedication, and clinical outcomes were analyzed by chart review.Results Urticaria occurred after the first injection in three patients and after the third or sixth injection in two. Onset was delayed (12-48 h) in all patients, indicating a non-IgE-mediated hypersensitivity. Four of five patients had a prior history of urticaria. All patients were re-exposed: two to the same anti-CGRP mAb and three to a different. Three patients received H1-antihistamine premedication. All premedicated patients in this series tolerated re-exposure, irrespective of switching. One patient experienced worsening urticaria with repeated dosing without premedication despite negative allergy testing, but later tolerated the same anti-CGRP mAb with premedication. In contrast, urticaria or angioedema recurred in two patients who switched anti-CGRP mAb without premedication. One subsequently tolerated rimegepant.Conclusion Anti-CGRP mAb-associated urticaria in this case series was delayed and likely non-immunoglobulin E (non-IgE)-mediated. Our experience supports that in selected patients with delayed urticaria, individualized management, including H1 antihistamine premedication, may allow continuation of effective migraine prophylaxis. Larger cohorts are needed to identify risk factors and to inform general management recommendations.