Migraine and its circulating markers of treatment resistance: an observational, prospective, open-label, randomized trial

BACKGROUND: Migraine is a disease with a complex pathogenesis and a significant frequency of treatment resistance. In the development of migraine attacks, the leading role is assigned to trigeminovascular system, associated with the release of proinflammatory cytokines and vasoactive molecules in the vessels of the dura mater.

AIM: To evaluate the circulating markers of inflammation and vasodilation in patients with frequent episodic and chronic migraine and their importance in predicting resistance to preventive treatment.

MATERIALS AND METHODS: 88 patients (average age is 35.05±0.95 years, women — 81%) with frequent episodic and chronic migraine were examined. At the beginning of the study, all subjects had vasodilating and inflammatory profile indicators in their blood once: calcitonin gene-related peptide (CGRP), vascular endothelial growth factor A (VEGF-A), tumor necrosis factor-alpha (TNF-α), transforming growth factor beta-1 (TGF-β1), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-18 (IL-18), gasdermin D, caspase 1. For three months, patients kept a headache diary and took preventive therapy in accordance with recommendations. The effect of therapy was evaluated based on the headache diary provided by patients in the end of the third month. ROC-analysis was used to analyze the prognostic value of the laboratory parameters used in relation to resistance to treatment of patients with migraine.

RESULTS: The prediction of treatment resistance in patients with migraine is possible by the level of IL-6 (area under the ROC-curve 0.716, p =0.028) and CGRP (area under the ROC-curve 0.695; p =0.047). The threshold value of IL-6 in the blood was 2.58 pg/mL (Sensitivity — 73%, Specificity — 70%), CGRP — 64.58 pg/mL (Sensitivity — 95%, Specificity — 58%).

CONCLUSION: The data obtained indicate the role of proinflammatory cytokines and vasoactive molecules in the development of resistance to preventive treatment of migraine. Subsequent studies on a larger sample are necessary to confirm the possibility of using IL-6 and CGRP levels to explain cases of migraine resistance to treatment and, potentially, the choice of therapy to correct the mechanisms associated with an increase in these indicators.