Research in context
Evidence before this study
We searched PubMed with the keywords “migraine AND preventive”, “CGRP”, “calcitonin gene-related peptide”, and “migraine preventives randomised controlled clinical trials”, for articles and clinical studies published in English in the past 10 years from Jan 1, 2010, to March 1, 2020. Several studies have shown that calcitonin gene-related peptide (CGRP) plays a role in the pathophysiology of headache disorders such as migraine. Galcanezumab is a humanised monoclonal antibody that potently and selectively binds to CGRP and prevents its biological activity without blocking the CGRP receptor. The prescription of CGRP monoclonal antibodies is approved in multiple countries for the preventive treatment of migraine. Publications of post-hoc analyses and two previous phase 3 trials (one with erenumab and one with fremanezumab) indicated that CGRP monoclonal antibodies might also be a safe and effective preventive option for patients who had multiple previous treatment failures.
Added value of this study
The results of this phase 3b, multicentre, randomised, placebo-controlled, double-blind, parallel trial show that monthly galcanezumab was safe and effective in patients for whom treatments had failed in two to four standard-of-care migraine preventive medication categories. More patients treated with galcanezumab had at least 75% and 100% reduction in monthly migraine headache days and greater improvement in functioning compared with patients treated with placebo. This study represents an important addition to the literature on galcanezumab and to the existing set of studies of CGRP antibodies as it not only included patients with both episodic and chronic migraine, but also included patients up to 75 years of age, thereby extending the age range previously evaluated for galcanezumab and the age range evaluated for the other CGRP monoclonal antibodies in a population for whom previous treatments had failed. This study also extends the results of previous studies in this population as it used a more stringent definition for treatment failure such that patients had to have actually tried the medications before they could be considered treatment failures; avoidance of a medication because of contraindication or unsuitability did not count toward the treatment-failure inclusion criterion.
Implications of all the available evidence
Galcanezumab 120 mg per month (with a 240-mg loading dose) is well tolerated and efficacious in the prevention of migraine in patients who had treatment failures of two to four categories of standard-of-care migraine preventive medications. Galcanezumab might represent an important treatment option for patients who have not benefited from or tolerated previous standard-of-care treatments.