Comparison of Early-onset Efficacy of Anti-calcitonin Gene-related Peptide Monoclonal Antibodies for Patients with Migraine in Real-world Clinical Practice: Study Protocol for an Exploratory Clinical Trial.

Abstract

Three anti-calcitonin gene-related peptide monoclonal antibodies (CGRP-mAbs) are available in Japan: galcanezumab, fremanezumab, and erenumab. Early-onset efficacy has been demonstrated for each CGRP-mAb in comparison with placebo, but differences among the drugs are unclear. Only galcanezumab requires 2 doses at the initial injection. This study is a multicenter, open-label, randomized, two-group comparison trial, consisting of the random selection of a CGRP-mAb and 6 consecutive injections, and then discontinuation of the CGRP-mAb after 6 injections. The primary outcome is a comparison of early-onset efficacy between galcanezumab and both fremanezumab and erenumab after the initial injection. The secondary outcomes are comparisons between galcanezumab and both fremanezumab and erenumab, and between fremanezumab and erenumab as follows: weekly number of headache days, migraine days, and acute medication use are compared to baseline during one month after initial injection; time of subjectively perceiving onset of effect after initial injection; monthly changes in headache status from baseline to after third (3rd) injections; effective rates after initial and 3rd injections; improvement rates of depression scores between baseline and after 3rd injections; changes in number of absenteeism and presenteeism days in each month from baseline to after 3rd injections; proportion of ineffective cases after 3rd injections; recurrence rates and time to recurrence after CGRP-mAb discontinuation; effective rates of CGRP-mAb re-injections; detection of clinical factors associated with effectiveness after the initial and 3rd injections. The aim of this study is to investigate differences in early-onset efficacy among the CGRP-mAbs, and when and to what extent headache symptoms recur after discontinuation.