AUTHOR=De Matteis Eleonora , Caponnetto Valeria , Casalena Alfonsina , Frattale Ilaria , Gabriele Amleto , Affaitati Giannapia , Giamberardino Maria Adele , Maddestra Maurizio , Viola Stefano , Pistoia Francesca , Sacco Simona , Ornello Raffaele 

TITLE=Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study

JOURNAL=Frontiers in Neurology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.973226

DOI=10.3389/fneur.2022.973226

ISSN=1664-2295

ABSTRACT=Objective: Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS are consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesize that patients with CAS might have a higher trigeminovascular activation than those without CAS leading to better response to anti-CGRP treatments. 
Methods: We performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e. erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e 12-week monthly headache days and 0-29%, 30-49%, 50-74%, 75%-99% and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal–Wallis test, and Mann–Whitney U test.
Results: Out of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, median difference in monthly headache days from baseline was higher in patients with UACs (-10, IQR -15 to -6) than in those without CAS (-6, IQR -12 to -3; P=0.009). However, the proportions of patients with 0-29%, 30-49%, 50-74%, 75%-99% and 100% response rate did not differ in the two groups.
Conclusions: In our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP-treatments.