Salivary CGRP and erenumab response: towards precision medicine in migraine

Abstract text (incl. figure legends and references)

Question: It is still to be shown if there is a correlation between baseline CGRP levels and prediction of response to these treatments or if CGRP levels are modified and how with treatment. We aimed (i) to analyze salivary CGRP levels in migraine patients (ii) to predict erenumab response from pre-treatment CGRP levels and (iii) to evaluate CGRP change post-treatment.

Methods: This is a prospective observational study that measured salivary CGRP levels in healthy controls (HC), episodic migraine (EM) and chronic migraine (CM) patients. Participants collected saliva samples at baseline and, patients who were candidates to receive erenumab 140 mg, also collected saliva after 3 doses of treatment. We quantified CGRP-like immunoreactivity (CGRP-LI) by ELISA and we performed an analysis at baseline and post-treatment through generalized linear mixed models.

Results: At baseline, a higher headache frequency was associated with higher CGRP levels, being those even higher in presence of depressive symptoms. A cut-off point of 103.75 pg/mL was estimated to differentiate migraine from controls with an 80.3% of accuracy. We also found that higher pre-treatment salivary CGRP levels were statistically significantly associated to a higher probability of having 50% or greater reduction in headache frequency in EM patients, but not in CM. After 12-weeks of treatment with erenumab 140, salivary CGRP levels from patients within all spectrum of migraine frequency converged to similar CGRP values. In contrast, in patients with concomitant depressive symptoms, this convergence did not happen.

Interpretation: Patients with migraine not only have higher CGRP levels compared to controls, but also the presence of depressive symptoms seems to increase salivary CGRP levels and we have evidence, for the first time, that salivary CGRP concentration is associated with treatment response to erenumab.