Central effects and affected somatosensory processing with galcanezumab in migraine

Galcanezumab alters central pain processing areas, such as the hypothalamus and cerebellum, in patients with migraine. In responders compared with non-responders to galcanezumab, specific decreases in activity in the hypothalamus were observed in a functional imaging study [1]. Furthermore, galcanezumab increased pain thresholds specifically in the trigeminal dermatome (V1), both in responders and non-responders with short-lasting modulatory effects [2].

Monoclonal antibodies (mAb) targeting calcitonin gene-related peptides (CGRP), such as CGRP-receptor antagonist erenumab and CGRP-ligand blocker galcanezumab, are a novel treatment class for migraine prevention. A previous (f)MRI study showed that erenumab had not only peripheral but additional central effects in patients with migraine. Moreover, anti-CGRP mAbs may modulate peripheral pain processing and differences in sensory thresholds may discriminate clinical responses [3].

Central effects of galcanezumab

Dr Hauke Basedau (University Medical Centre Hamburg-Eppendorf, Germany) hypothesised that galcanezumab would alter trigeminal central pain processing; that responders to galcanezumab would show modulation of specific central areas (specifically in the hypothalamus) in contrast to non-responders; and that the efficacy can be predicted as early as day 1, i.e. before administration.

Dr Basedau and colleagues conducted an fMRI study that included 26 patients with migraine using an established trigeminal nociceptive paradigm with gaseous ammonia. The current study assessed the patients before and 2–3 weeks after the administration of galcanezumab. Results indicated that galcanezumab reduced hypothalamic activation, which was more prominent in responders versus non-responders. “We concluded that there is a central effect associated with the administration of galcanezumab,” said Dr Basedau.

Furthermore, results indicated that the activity of the spinal trigeminal nucleus followed by trigemino-nociceptive stimulation before treatment covaried with the response to galcanezumab. The functional connectivity between the spinal trigeminal nucleus and the hypothalamus was found to decrease after galcanezumab administration. The more the spinal trigeminal nucleus was activated due to painful stimulation before galcanezumab administration, the higher the likelihood of responding to galcanezumab. “Quite interesting is that this is approximately the same hypothalamic area that we have already found as the corpus delicti for an increase in headache base, or at least being an area of interest in migraine-associated headache,” concluded Dr Basedau.

Effect on somatosensory processing

In a second analysis, the 26 patients also underwent quantitative sensory tests before and 2–3 weeks after galcanezumab administration [2]. Dr Kuan-Po Peng (University Medical Centre Hamburg-Eppendorf, Germany) shared the results of this study.

After the administration of galcanezumab, the heat pain threshold and mechanical pain threshold increased significantly (P<0.05), but exclusively in the V1 dermatome and not on the forearm. Changes between the before and after measurements did not differ regarding clinical response. A clinical responder was defined as having a ≥30% reduction in headache frequency after 3 months of treatment.

Baseline heat pain threshold predicted a clinical response and inversely correlated with the baseline headache frequency, suggesting that clinical response may be associated with individual susceptibility and disease activity.

1. Basedau H, et al. Galcanezumab has central effects in the migraine brain. AL069, IHC 2021, 8–12 September.
2. Peng K-P, et al. Galcanezumab changes somatosensory perception exclusively in the face, whereas heat pain threshold before treatment predicts efficacy. AL062, IHC 2021, 8–12 September.
3. Ziegeler C, et al. Neurology. 2020;95(20):e2794–802.

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Posted on 8 November 20211 February 2024