Proposal of combination therapies to treat refractory chronic migraine

Chronic migraine, affecting people for over 15 days per month of which 8 show migraine features, severely reduces patients’ quality of life with great rate of associated disability. Onabotulinumtoxin A has been used in the prevention of chronic migraine for the last two decades. A recent pooled analysis of real-world data highlighted the efficacy of its use in combination with the most novel monoclonal antibodies targeting the machinery of the calcitonin gene-related peptide (CGRP) in refractory migraine. Moreover, the CRD42023393250 systematic review and meta-analysis registered in the National Institute for Health Research International prospective register of systematic reviews PROSPERO following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement supported the safety of onabotulinumtoxin A, demonstrating that it induces fewer treatment-related adverse events (TRAEs) than oral topiramate one of the most commonly used preventative drugs. Therefore, the present data together with the lack of appropriately designed, prospective studies prompt the proposal of clinical trials to assess the efficacy and safety of the combination treatment of onabotulinumtoxinA with monoclonal antibodies or gepants directed towards the pathway of CGRP.