Migraine monoclonal antibodies against CGRP change brain activity depending on ligand or receptor target – an fMRI study

Background: Monoclonal antibodies (mAbs) against calcitonin gene-related peptides (CGRP) are novel treatments for migraine prevention. Based on a previous functional imaging study which investigated the CGRP receptor mAb (erenumab), we hypothesized that (i) the CGRP ligand mAb galcanezumab would alter central trigeminal pain processing; (ii) responders to galcanezumab treatment would show specific hypothalamic modulation in contrast to non-responders; and (iii) the ligand and the receptor antibody differ in brain responses.
Methods: Using an established trigeminal nociceptive functional magnetic imaging paradigm, 26 migraine patients were subsequently scanned twice: before and 2–3 weeks after administration of galcanezumab.
Results: We found that galcanezumab decreases hypothalamic activation in all patients and that the reduction was stronger in responders than in non-responders. Contrasting erenumab and galcanezumab showed that both antibodies activate a distinct network. We also foun..., Experimental paradigm
Patients were asked to attend two functional magnetic resonance imaging (fMRI) scanning sessions before and after the first administration of galcanezumab. Both visits took place approximately three weeks apart (pharmacokinetic drug peak blood level) and followed the same protocol. Following the first scan, the loading dose of galcanezumab 240 mg was administered subcutaneously by the patient under the prior instruction of a headache specialist.
During the experiment, which has been described in detail previously, participants received 15 repetitive painful trigeminal stimulations by administering gaseous ammonia (mixed in a stream of air) into the left nostril and 15 puffs of air, 15 trials of rose scent and 15 repetitive visual stimuli as control conditions. All stimuli were presented in a pseudo-randomized order, with painful trigeminal stimuli not presented in immediate succession. After each trial, participants were asked to rate the intensity as well as the u...,