PO-86 | CGRP, VIP and PACAP plasmatic levels in migraine patients before and after anti-CGRP(R) monoclonal antibodies prophylaxis

Background: 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 plasma levels of these neuropeptides before and after prophylactic treatment with anti-CGRP(R) mAbs, evaluating potential changes after therapy and identifying predictors of treatment response 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 (MMDs) after six months. Blood samples were collected at baseline and at each follow-up visit (baseline T0, 3 months T1, 6 months T2, 12 months T3). Plasma levels of CGRP, VIP, and PACAP were measured using a validated radioimmunoassay (RIA) and commercially available enzyme-linked immunosorbent assay (ELISA) kits. Results: Overall, 80.3% (45 out of 56) of patients responded to anti-CGRP(R) mAbs. In patients treated with erenumab, CGRP levels did not show a significant change over the treatment period; however, responders exhibited a decreasing trend from T0 to T2 compared to non-responders. In the galcanezumab group, CGRP levels significantly decreased as early as T1 (p < 0.01). Conversely, in the fremanezumab group, we observed a rapid increase in CGRP plasma levels above 3000 pg/ml, which was deemed unreliable due to assay interference from fremanezumab. VIP and PACAP levels remained stable over time, with no significant differences between responders and non-responders Conclusion: Anti-CGRP(R) mAbs are very effective migraine prophylaxes. Galcanezumab reduced CGRP plasmatic levels already after three months, while erenumab did not affect significantly CGRP plasmatic levels. VIP and PACAP levels were not influenced by the therapy.