CGRP, VIP and PACAP plasmatic levels in migraine patients before and after anti-CGRP(R) monoclonal antibodies treatment

Aim Calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) play a crucial role in migraine pathophysiology. In recent years, anti-CGRP(R) monoclonal antibodies (mAbs) have emerged as the first targeted and highly effective therapy for migraine. This study aimed to assess any changes in plasma CGRP levels following prophylactic treatment with anti-CGRP(R) mAbs and to compare CGRP dynamics between anti-receptor (erenumab) and anti-ligand (galcanezumab, fremanezumab) therapies. Secondary objectives were: (i) to evaluate changes in VIP and PACAP plasma levels following treatment with anti-CGRP(R) mAbs and (ii) to investigate whether baseline or post-treatment plasma levels of CGRP, VIP and PACAP were associated with clinical response to anti-CGRP(R) monoclonal antibody therapy. Methods Between February 2022 and February 2023, we enrolled 56 migraine patients who initiated prophylaxis with either erenumab (26 patients), galcanezumab (16 patients) or fremanezumab (14 patients). Responders were defined as those achieving a ≥50% reduction in monthly migraine days after six months. Blood samples were collected at baseline and at each follow-up visit (baseline, T0; three months, T1; six months, T2; 12 months, T3). Plasma levels of CGRP, VIP and PACAP were measured using a validated radioimmunoassay and commercially available enzyme-linked immunosorbent assay kits. Results Overall, 80.3% (45 out of 56) of patients responded to anti-CGRP(R) mAbs. No correlation was found between baseline CGRP, VIP and PACAP plasma levels and clinical response to anti-CGRP(R) mAbs therapy. Regarding CGRP trend, significant differences were found between patients treated with the anti-receptor monoclonal antibody (erenumab) and those receiving anti-ligand therapies. In patients treated with erenumab, CGRP levels did not show a significant change over the treatment period (T1–T3), whereas, in the galcanezumab group, CGRP levels significantly decreased as early as T1 ( p < 0.01). CGRP longitudinal assessment of the fremanezumab group were excluded due to assay interference with the drug. VIP and PACAP plasma levels remained stable over time for all treatments, with no significant differences between responders and non-responders. Conclusions Galcanezumab reduced CGRP plasmatic levels already after three months, whereas erenumab did not affect significantly CGRP plasmatic levels. VIP and PACAP levels were not influenced by the therapy.