New migraine prophylactic drugs: Current evidence and practical suggestions for non-responders to prior therapy

• Published in: Cephalalgia Vol. 43; no. 2; p. 3331024221146315
• Main Authors: Lee, Mi Ji, Al-Karagholi, Mohammad Al-Mahdi, Reuter, Uwe
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.02.2023
• Subjects: Botulinum Toxins, Type A - therapeutic use; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide Receptor Antagonists - therapeutic use; Humans; Migraine Disorders - drug therapy; Migraine Disorders - prevention & control; Receptors, Calcitonin Gene-Related Peptide - metabolism; Refractory; eptinezumab; gepant; erenumab; fremanezumab; galcanezumab
• ISSN: 0333-1024; 1468-2982; 1468-2982
• DOI: 10.1177/03331024221146315

Background Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor (anti-CGRP(-R) mAbs) and small-molecule CGRP receptor antagonists (gepants) are new mechanism-based prophylactic drugs developed to address the unmet needs of pre-existing migraine prophylactic medications. However, several uncertainties remain in their real-world applications. Methods This is a narrative review of the literature on the use of CGRP-targeting novel therapeutics in specific situations, including non-responders to prior therapy, combination therapy, switching, and treatment termination. In the case of lack of available literature, we made suggestions based on clinical reasoning. Results High-quality evidence supports the use of all available anti-CGRP(-R) mAbs (erenumab, galcanezumab, fremanezumab, and eptinezumab) in non-responders to prior therapy. There is insufficient evidence to support or reject the efficacy of combining CGRP(-R) mAbs or gepants with oral migraine prophylactic agents or botulinum toxin A. Switching from one CGRP(-R) mAb to another might benefit a fraction of patients. Currently, treatment termination depends on reimbursement policies, and the optimal mode of termination is discussed. Conclusions New prophylactic drugs that target the CGRP pathway are promising treatment options for patients with difficult-to-treat migraine. Individualized approaches using a combination of new substances with oral prophylactic drugs or botulinum toxin A, switching between new drugs, and adjusting treatment duration could enhance excellence in practice.