Objective:

To describe a desensitization protocol for patients with immediate eptinezumab hypersensitivity.

Background:

Eptinezumab is a humanized monoclonal antibody targeting calcitonin gene-related peptide (CGRP), approved for migraine prevention. While generally well-tolerated, hypersensitivity reactions have been documented.

Design/Methods:

Case series and review of the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS).

Results:

Patient 1 is a 33-year-old female with chronic migraine, on eptinezumab for four years, who developed cough, throat swelling, and urticaria within ten minutes of her last eptinezumab 300 mg infusion. She was treated in the emergency department (ED), requiring epinephrine, and discharged on prednisone and anti-histamines, but returned the following day with recurrent throat swelling and urticaria. She was switched to rimegepant 75 mg every other day but also experienced shortness of breath and urticaria. Her headache severity worsened off eptinezumab. She had previously trialed multiple anti-seizure medications, anti-depressants, anti-hypertensives, other anti-CGRP medications, memantine, cyproheptadine, nerve blocks, and neuromodulation. As eptinezumab 300 mg was the only effective treatment for this patient with severe, treatment-experienced, chronic migraine, eptinezumab desensitization was planned. She tolerated a three-bag 12-step eptinezumab desensitization with only subjective symptoms, managed with diphenhydramine. A localized port-site rash developed after the second two-bag, eight-step desensitization; a third is planned. Patient 2 is a 24-year-old female with chronic migraine on eptinezumab for the preceding three years, who developed recurrent sneezing, flushing, throat tightness, voice changes, and shortness of breath after her most recent eptinezumab 300 mg infusion, requiring epinephrine in the ED. She is currently undergoing eptinezumab desensitization protocol. A review of FAERS revealed 259 cases of hypersensitivity reaction to eptinezumab, with 39 classified specifically as an anaphylactic reaction, although no deaths. 

Conclusions:

Eptinezumab can induce hypersensitivity reactions in 1-4% of patients. Desensitization may allow patients to receive eptinezumab when no equally effective alternatives are available.