Trigeminal sensory modulatory effects of galcanezumab and clinical response prediction

Abstract

Galcanezumab, a monoclonal antibody against calcitonin gene-related peptide, is an emerging migraine preventative. We hypothesized that the preventive effects are conveyed via the modulation of somatosensory processing and that certain sensory profiles may hence be associated with different clinical responses. We recruited migraine patients (n 5 26), who underwent quantitative sensory tests over the right V1 dermatome and forearm at baseline (T0), 2 to 3 weeks (T1) and 1 year (T12) after monthly galcanezumab treatment. The clinical response was defined as a reduction of $30% in headache frequency based on the headache diary. Predictors for clinical response were calculated using binary logistical regression models. After galcanezumab (T1 vs T0), the heat pain threshold (˚C, 44.9 6 3.4 vs 43.0 6 3.3, P 5 0.013) and mechanical pain threshold (log mN, 1.60 6 0.31 vs 1.45 6 0.26, P 5 0.042) were increased exclusively in the V1 dermatome but not the forearm. These changes were immediate, did not differ between responders and nonresponders, and did not last in 1 year of follow-up (T12 vs T0). However, baseline heat pain threshold (OR: 2.13, 95% CI: 1.08-4.19, P 5 0.029) on the forearm was a robust predictor for a clinical response 3 months later. In summary, our data demonstrated that galcanezumab modulates pain thresholds specifically in the V1 dermatome, but this modulation is short-lasting and irrelevant to clinical response. Instead, the clinical response may be determined by individual sensibility even before the administration of medication.

Pre-treatment non-ictal cephalic allodynia identifies responders to prophylactic treatment of chronic and episodic migraine patients with galcanezumab: A prospective quantitative sensory testing study (NCT04271202)

“…Incorporating the concept that the baseline excitability and responsivity state of central trigeminovascular neurons (as reflected by enhanced sensitivity to skin stimulation) that mediate the headache phase of migraine could determine outcome of prophylactic treatment of migraine, Wang and his colleagues (11) reported recently that the prophylactic treatment of chronic migraine (CM) with the calcium channel blocker flunarizine was significantly more effective in those participants whose skin sensitivity to mechanical and thermal stimulation of the periorbital region was relatively normal, in comparison to those whose periorbital skin sensitivity was abnormally heightened. Somewhat similarly, May and colleagues (12) reported that the pre-treatment forearm heat pain threshold of migraine patients whose number of migraine days per month (MMD) decreased by >30% following a three-month period of galcanezumab treatment was significantly higher (45.2°C) than in those who failed to achieve the 30% reduction in MMD (44.3°C).…”

A Scoping Review and Meta-Analysis of Anti-CGRP Monoclonal Antibodies: Predicting Response

“…This association was especially evident in cephalic allodynia (OR for ≥50% response: 0.037, 95% CI: 0.004-0.181), but was also seen with extra-cephalic allodynia (OR for ≥50% response: 0.188, 95% CI: 0.022-0.954). A higher heat pain threshold, which represents a lower sensitivity to thermal stimuli and predicted a good response to CGRP(-R) mAbs (OR for higher heat pain thresholds in • C: 2.57, 95% CI: 1.08-6.11), was found in another study [44]. In Pensato et al [68], the presence of allodynia as a clinical symptom was associated with nonresponse after 3 months of treatment with CGRP(-R) mAbs (OR for ≥50% response: 0.47, 95% CI: 0.24-0.94).…”

A history of International Headache Society grants and their impact on headache careers

“…Of these, currently 77% have obtained an academic position, which in over half the cases involves headache. Ten former IHS fellows have published at least one first author paper in collaboration with the host institution, and several of these publications have been accepted in high impact journals ( 2 – 11 ). Figure 1 shows the country of origin and of destination of all recipients of the IHS Fellowship.…”