A multidisciplinary multicentric approach to the identification of predictive biomarkers of response to erenumab - the protocol of the phase 4, European, open-label controlled trial of the BIOMIGA project.

BACKGROUND: Migraine is a highly prevalent disease and the leading cause of years lived with disability in women. The development of therapies targeting the calcitonin gene-related peptide (CGRP) pathway has provided the first mechanism-based approach for migraine prevention. Although these treatments have demonstrated substantial efficacy, 30-50% of patients do not achieve an adequate clinical response. This variability underscores the need of prospectively identifying responders and non-responders, thereby enabling precise treatment allocation and improving clinical outcomes. OBJECTIVES: BIOMIGA is a multicentre phase IV study aimed at identifying biomarkers of response to anti-CGRP therapy in migraine through integrated clinical, molecular, genetic, and neuroimaging profiling, with patients stratified according to treatment response after 3 months treatment cycle with an mAB targeting the CGRP receptor (erenumab). METHODS: Individuals with episodic and chronic migraine eligible for treatment with erenumab are enrolled along with healthy control subjects. Biomarkers are collected longitudinally at baseline and at the end of a 3-month treatment with erenumab. Circulating levels of CGRP and cytokines, genetic polymorphisms, and DNA methylation are assessed. Advanced structural and functional MRI scans are performed simultaneously, and comprehensive psychometric scales are used to map central pain processing and clinical burden. The final multimodal dataset is analysed using machine learning to develop and evaluate integrated models of treatment response. EXPECTED RESULTS: The integration of multimodal data from patients and healthy controls, stratified according to treatment response, will enable the identification of a panel of biomarkers predictive of response to anti-CGRP therapy. CONCLUSION: The BIOMIGA trial represents a major step forward in the management of migraine. By combining a comprehensive multimodal profiling with a real-world, multicentre cohort of patients treated with erenumab, the study provides a framework for identifying robust biomarkers of treatment response and lays the foundation for truly individualised migraine prevention strategies. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04503083.