Onset, Maintenance, and Cessation of Effect of Galcanezumab for Prevention of Migraine: A Narrative Review of Three Randomized Placebo-Controlled Trials.

ABSTRACT

INTRODUCTION: Galcanezumab, a humanized monoclonal antibody that binds to calcitonin gene-related peptide, is approved for the preventive treatment of migraine in adults. It is self-administered once monthly as a subcutaneous injection. This paper describes the time course of effect of galcanezumab in patients with episodic and chronic migraine. METHODS: Data were based on three double-blind, placebo-controlled, phase 3 studies. Patients (1773 episodic and 1113 chronic) were randomized (211) to monthly doses of placebo, galcanezumab 120 mg with a 240 mg loading dose, or galcanezumab 240 mg (January 2016-March 2017). Onset of effect was determined using a sequential analysis approach based on earliest time point at which galcanezumab achieved and subsequently maintained statistical superiority to placebo. Maintenance of effect was a comparison of the percentages of galcanezumab- and placebo-treated patients with maintenance of at least 50% response at the individual patient level. Cessation of effect was determined during a 4-month post-treatment period on the basis of change from baseline in monthly migraine headache days. RESULTS: Galcanezumab led to a lower percentage of patients who had a migraine headache on the first day after injection, provided maintenance of effect throughout the duration of the double-blind treatment period, and gradually lost effect without signs of rebound headache throughout the post-treatment period in most patients with episodic and chronic migraine. CONCLUSION: Galcanezumab is a novel preventive therapeutic option for adult patients with migraine that has early onset of action, maintenance of effect, and gradual reduction of effect upon treatment cessation. TRIAL REGISTRATION ClinicalTrials.gov NCT02614183 (EVOLVE-1); NCT02614196 (EVOLVE-2); NCT02614261 (REGAIN).