Efficacy and safety of mAbs anti-CGRP/CGRP R (eptinezumab and erenumab) or atogepant in combination with onabotulinumtoxinA in refractory chronic migraine: a clinical trial protocol

Abstract

Chronic migraine is a disabling neurovascular disorder that represents the leading cause of years lived with disability in people under 50 with a remarkable social burden due to widespread resistance to the front-line treatments used routinely in current clinical practice. The present study investigates the efficacy and safety of combination therapy using eptinezumab and erenumab, recently approved monoclonal antibodies (mAbs) directed against calcitonin gene-related peptide or its receptor, respectively, or the receptor competitive antagonist atogepant together with botulinum toxin type A in chronic migraine that has proven resistant to front-line treatments for at least 6 weeks. To this aim a retrospective and a prospective phase are designed. Furthermore, a feasible salivary biomarker of migraine is under investigation in the prospective stage of the study. Based on recent expert opinions supporting the switch to easy-to-use small molecule calcitonin gene-related peptide (CGRP)-targeting, i.e. rimegepant or atogepant in unresponsive patients, the present study may offer to clinicians a novel treatment to enhance the therapeutic preventive machinery in chronic migraine.

Keywords: CGRP receptor antagonists; anti-CGRP monoclonal antibodies; anti-CGRP-R monoclonal antibodies; atogepant; chronic migraine; gepants; onabotulinumtoxinA.