Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

Comparison of the blink reflex in classical and idiopathic trigeminal neuralgia.

BACKGROUND: Previous findings indicate that the blink reflex is useful to distinguish between primary (classical/idiopathic) and secondary trigeminal neuralgia. No prior studies have investigated whether the blink reflex could identify differences in electrophysiological responses between classical and idiopathic trigeminal neuralgia. With this in mind, we investigated the blink reflex in a cohort of classical and idiopathic trigeminal neuralgia patients. METHODS: Participants were consecutively enrolled in the study. According to magnetic resonance imaging findings, the patients were subgrouped into either classical or idiopathic trigeminal neuralgia. Assessors were blinded to the subgroup and pain side, and the blink reflex was examined to assess R1 and R2 latencies, as well as the area under the curve. RESULTS: The study group constituted of 55 patients with primary trigeminal neuralgia: 25 patients with classical trigeminal neuralgia and 30 patients with idiopathic trigeminal neuralgia. None of the blink reflex latencies (R1 and R2) or the area under the curve significantly differed between the two subgroups when adjusted for age and sex (p > 0.05). CONCLUSIONS: Our findings suggest that the blink reflex cannot be used to differentiate classical and idiopathic trigeminal neuralgia patients, and that both subgroups may share common pathophysiological mechanisms.Trial Registration: ClinicalTrials.gov Identifier: NCT05328661.

Peripheral changes of endocannabinoid system components in episodic and chronic migraine patients: A pilot study.

BACKGROUND: Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine. METHODS: The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components. RESULTS: Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake. CONCLUSION: The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field.clinicaltrials.gov NTC04324710.