Abstract
BackgroundMigraine prevention with erenumab and migraine induction by calcitonin gene-related peptide (CGRP) both carry notable individual variance. We wanted to explore a possible association between individual efficacy of anti-CGRP treatment and susceptibility to migraine induction by CGRP.MethodsThirteen migraine patients, previously enrolled in erenumab anti-CGRP receptor monoclonal antibody trials, received CGRP in a double-blind, placebo-controlled, randomized cross-over design to investigate their susceptibility to migraine induction. A standardized questionnaire was used to assess the efficacy of previous antibody treatment. The patients were stratified into groups of high responders and poor responders. Primary outcomes were incidence of migraine-like attacks and area under the curve of headache intensity after infusion of CGRP and placebo. All interviews and experiments were performed in laboratories at the Danish Headache Center, Copenhagen, Denmark.ResultsTen high responders and three poor responders were included. CGRP induced migraine-like attacks in ten (77%) patients, whereof two were poor responders, compared to none after placebo (p = 0.002). The area under the curve for headache intensity was greater after CGRP, compared to placebo, at 0–90 min (p = 0.009), and 2–12 h (p = 0.014). The median peak headache intensity score was 5 (5–9) after CGRP, compared to 2 (0–4) after placebo (p = 0.004).ConclusionsPatients with an excellent effect of erenumab are highly susceptible to CGRP provocation. If an association is evident, CGRP provocation could prove a biomarker for predicting antibody treatment efficacy.Trial registrationRetrospectively registered at clinicaltrials.gov with identifier: NCT03481400.
Highlights
Migraine prevention with erenumab and migraine induction by calcitonin gene-related peptide (CGRP) both carry notable individual variance
Calcitonin gene-related peptide induces migraine-like attacks in an average of 62% of migraine patients across placebo-controlled and open-label provocation studies. [8–11] Individual differences in Monoclonal antibody (mAb) efficacy and migraine induction suggest that CGRP involvement in migraine varies between patients, and susceptibility to provocation could be a possible biomarker for anti-CGRP treatment efficacy
All 13 patients were enrolled after completing the safety follow-up visit 12 weeks after the last dose of erenumab
Summary
Migraine prevention with erenumab and migraine induction by calcitonin gene-related peptide (CGRP) both carry notable individual variance. We wanted to explore a possible association between individual efficacy of anti-CGRP treatment and susceptibility to migraine induction by CGRP. [1] Four anti calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) are in late-phase development as the first class of preventive therapeutics targeting migraine-specific mechanisms. Calcitonin gene-related peptide induces migraine-like attacks in an average of 62% of migraine patients across placebo-controlled and open-label provocation studies. [8–11] Individual differences in mAb efficacy and migraine induction suggest that CGRP involvement in migraine varies between patients, and susceptibility to provocation could be a possible biomarker for anti-CGRP treatment efficacy. We sought to investigate a possible association between anti-CGRP treatment efficacy and susceptibility. Clinicians treating migraine have, until now, been limited to preventive drugs that were initially developed for cardiovascular, psychiatric or neurological diseases other than migraine. [1] Four anti calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) are in late-phase development as the first class of preventive therapeutics targeting migraine-specific mechanisms. [2] Three mAbs (fremanezumab, eptinezumab and galcanezumab) are ligand specific, and bind to CGRP, while one (erenumab) binds to the receptor complex (Fig. 1). [3–6] Overall efficacy and tolerability between the four
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