Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: A real-world evidence study

Abstract

Background Clinical trials on anti-calcitonin gene-related peptide monoclonal antibodies poorly investigated their impact on migraine accompanying symptoms. Objective To evaluate the impact of basal accompanying symptoms on anti-CGRP monoclonal antibodies treatment response and their evolution after six months of treatment in migraine patients. Methods Patients with migraine diagnosis seen in the Headache Clinic and treated with erenumab, galcanezumab or fremanezumab were prospectively recruited. They completed a daily eDiary which provided data on headache frequency and the following accompanying symptoms of each day: photophobia, phonophobia, nausea, dizziness, and aura. Patients were classified as responders or non-responders based on 50% or greater reduction in headache days per month at month 6 (≥50% response rate). Accompanying symptoms ratios based on headache days per month were assessed per patient at baseline and after three and six months. Comparisons for basal characteristics, basal accompanying symptoms ratios and their evolution after six months between responders and non-responders were performed. Results One hundred and fifty-eight patients were included, 44% (69/158) showed ≥50% response rate after six months. A significant reduction in headache days per month in both groups was found at month 6 (−9.4 days/month in ≥50% response rate group; p < 0.001, −2.2 days/month in <50% response rate group; p = 0.004). Additionally, significant decreases in photophobia (−19.5%, p < 0.001), phonophobia (−12.1%, p = 0.010) and aura ratios (−25.1%, p = 0.008) were found in ≥50% response rate group. No statistically significant reductions were found in nausea and dizziness in any group since their reduction was correlated with the decrease in headache days per month. Higher photophobia ratios at baseline were predictive of an increased response between months 3 and 6 (Incidence Risk Ratio = 0.928, p = 0.040). Conclusions The days per month with photophobia, phonophobia and aura decreased at a higher rate than headache days per month after six months in the ≥50% response group. Higher photophobia ratios were associated with higher response rates between three and six months. It could indicate an involvement of peripheral CGRP in photophobia as well as a central modulation of migraine through these treatments which mainly act on the periphery.