Serum alpha and beta-CGRP levels in chronic migraine patients before and after monoclonal antibodies against CGRP or its receptor.

Abstract

To analyse the evolution of alpha and beta-CGRP circulating levels throughout CGRP monoclonal antibodies (mAb) treatment in chronic migraine (CM) patients. We recruited CM patients beginning mAb along with sex and age paired healthy controls (HC). Blood was extracted before, two-weeks (M0.5) and three months (M3) after first dose of mAb, always in free-migraine periods, and once for HCs. Alpha and beta-CGRP serum levels were measured using ELISAs specific for each isoform. Baseline alpha-CGRP levels were significantly elevated in 103 CM patients (median [95% CI]: 50.3 [40.5-57.0] pg/mL) compared to 78 HC (37.5 [33.9-45.0] pg/mL; 95% CI of differences: 2.85-17.08 pg/mL) and significantly decreased (n=96) over the course of mAb treatment (M0.5: 40.4 [35.6-48.2] pg/mL; M3: 40.9 [36.3-45.9] pg/mL). Absolute decrease of alpha-CGRP throughout the treatment positively correlated with the decrease in monthly migraine days. Negative modulation of alpha-CGRP significantly associated with positive scores at the patient global impression of change scale and with analgesic overuse reversal. Beta-CGRP did not differ at baseline between CM patients (4.2 [3.0-4.8] pg/mL) and HC (4.4 [3.4-5.6] pg/mL; -1.09 to 0.60) nor was modulated by mAb treatment (n=96) (M0.5: 4.5 [3.5-5.2] pg/mL; M3: 4.6 [3.7-5.2] pg/mL). Treatment with mAb, regardless of its target, is able to progressively normalize basally increased alpha-CGRP levels in CM and this effect correlates with efficacy measures, which supports a role of this neuropeptide as the first CM biomarker. This article is protected by copyright. All rights reserved.