Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies

Abstract

Discontinuation of treatment with monoclonal antibodies (mAb) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway leads to an increase in migraine frequency. We aimed to assess changes in free and total CGRP plasma concentrations after the discontinuation of CGRP(-receptor) mAbs. This prospective analysis included 59 patients with migraine (n = 25 erenumab, n = 25 galcanezumab, n = 9 fremanezumab) who discontinued mAbs after ≥8 months of treatment. Patients were visited at the time of the last mAb injection (V1) and 16 weeks later (V2). For control, 30 migraine patients without preventive drug therapy were included. We measured free CGRP plasma concentrations in the erenumab and fremanezumab group and total CGRP concentrations in the galcanezumab group. Free CGRP plasma concentrations did not change after treatment discontinuation [erenumab: V1 31.2 pg/mL (IQR 25.8–45.6), V2 30.3 pg/mL (IQR 22.9–47.6), p = 0.65; fremanezumab V1 29.4 pg/mL (IQR 16.4–61.9), V2 34.4 (19.2–62.0), p = 0.86]. Controls had similar CGRP values of 32.6 pg/mL (IQR 21.3–44.6). Total CGRP concentrations in the galcanezumab group were 5439.3 pg/mL (2412.7–6338.1) at V1, and decreased to 1853.2 pg/mL (1136.5–3297.0) at V2 (p < 0.001). Cessation of treatment with CGRP(-R) mAbs did not have an impact on the free-circulating CGRP concentrations. Total CGRP decreased significantly after three months of treatment discontinuation.

Glycerol Trinitrate Acts Downstream of Calcitonin Gene-Related Peptide in Trigeminal Nociception—Evidence from Rodent Experiments with Anti-CGRP Antibody Fremanezumab

“…We have seen no significant difference in CGRP concentration between the ganglia of rats treated with fremanezumab versus the control antibody, which is consistent with our previous findings, although it contrasts with a decrease in CGRP immunoreactive trigeminal ganglion neurons [29]. The lack of change in CGRP concentration is reminiscent of a recent clinical study in which plasma CGRP levels in patients were determined during the treatment with fremanezumab and four months after discontinuation of the treatment [38]. CGRP plasma concentrations did not differ between during treatment and post-treatment and were on the same level as in healthy controls.…”

Untangling the mess of CGRP levels as a migraine biomarker: an in-depth literature review and analysis of our experimental experience

“…This is the reason why ELISA-based studies are also subjected to the exact same issues associated with RIA-based works. As it has been described, investigations using the same brand also reports similar peptide concentration ranges [ 25 , 26 , 30 , 44 , 49 , 67 ], even though this is not always the case [ 32 ], but, most importantly, those using different kits clash in the range of concentrations [ 23 , 61 , 62 ] on top of the conclusions drawn [ 33 , 61 ]. For this point we need to explain that kits from USCN Life Sciences and Cloud Clone Corp., and from Peninsula Laboratories and BMA Biomedicals have been considered as only two brands since these companies have merged or have been acquired by the other at some point in their history.…”