INTRODUCTION: Migraine and cluster headache are challenging to manage, with no tailored preventive medications available. Targeting the calcitonin gene-related peptide (CGRP) pathway to treat these headaches may be the first focused therapeutic option to date, with the potential for promising efficacy.

METHODS: We systematically searched PubMed and clinicaltrials.gov for randomized controlled trials investigating the preventive potential of monoclonal antibodies against the CGRP pathway in the treatment of migraine and cluster headache.

RESULTS: The literature search returned a total of 136 records, of which 32 were eligible for review.

DISCUSSION: Clinical data from phase II and III trials of the four monoclonal antibodies targeting the CGRP pathway: Eptinezumab, erenumab, fremanezumab, and galcanezumab, collectively show a positive effect in the preventive treatment of episodic and chronic migraine. Multiple phase II and III trials are under way to further determine the efficacy and safety of this new drug class. It may be particularly important to assess the cardiovascular effects of long-term CGRP blockade. Phase III trials are also currently in progress for the preventive treatment of cluster headache.

CONCLUSION: Efficacy of anti-CGRP monoclonal antibodies spells a promising future for the many patients suffering from migraine, and possibly also for the smaller but severely-affected population with cluster headache.