PO-16 | Neurophysiological effects of atogepant in high-frequency episodic migraine (ATOM)

Background: Atogepant is a novel oral preventive migraine treatment acting as a calcitonin gene-related peptide (CGRP) receptor antagonist. Our study aims to investigate the impact of a 3-monht course of atogepant treatment on neurophysiological markers of central sensitization and habituation. Methods: This is a prospective study enrolling subjects with high-frequency episodic migraine (HFEM) presenting 8-14 monthly migraine days (MMDs). Neurophysiological assessments were performed during the inter-ictal phase according to standardized protocols. These included evaluation of the nociceptive withdrawal reflex (single stimulus threshold – RTh, and temporal summation threshold – TST) of the lower limb, the nociceptive blink reflex (nBR), and visual evoked potentials (VEPs). Participants were assessed at baseline (T0) and after three months of daily atogepant 60 mg intake (T1). Responders achieved a reduction of at least 50% in monthly migraine days at T1. Results: We enrolled 22 subjects with HFEM (37.7 ± 11.8 years, 16 females). At baseline they presented a mean of 10.2 ± 2.0 MMDs associated with a high migraine-related disability (MIDAS T0: 45.4 ± 29.4). Atogepant determined a reduction in MMDs and MIDAS score (MMDs T1 4.8 ± 3.7, p<0.001 vs. T0, MIDAS T1 8.6 ± 10.4, p<0.001 vs. T0). Responder rate at T1 was 68.2% (15/22). At T1 we found an increase in the RIII reflex threshold (T0: 13.3 ± 5.7 vs. T1: 15.8 ± 6.7, p<0.001), but not in the TST (T0: 9.3 ± 4.6 vs. T1: 10.3 ± 4.6, p<0.389). nRB assessed at 0.2Hz, 0.3Hz and 0.5Hz showed a baseline habituation, confirmed at T1 (Factor BLOCK p<0.001 for all comparisons). At 0.2Hz we observed a reduction in the area of the first block at T1 (T0: 1.48±0.9 μVxms p<0.001 vs. T1: 1.0 ± 0.5μVxms, p=0.050). PEV evaluation showed a lack of habituation both at T0 and T1 (habituation index – HI T0: 92.2 ± 22.1 vs. T1 93.2 ± 13.1, p=0.794). Conclusion: Our findings suggest that atogepant treatment induces an improvement in central sensitization mechanisms and a modulation of the habituation pattern. Further studies are needed to assess whether the observed results are a direct atogepant effect or a compensatory mechanism related to clinical improvement.