The association between onabotulinumtoxinA and anti-CGRP monoclonal antibodies: a reliable option for the optimal treatment of chronic migraine

Chronic migraine (CM) is a great challenge for physicians dealing with headaches. Despite the introduction of the monoclonal antibodies (mAbs) acting against the calcitonin gene-related peptide (CGRP) that has revolutionized the treatment of CM, some patients still experience an incomplete relief. So, the association of two preventive treatments may be a reliable option for these patients. So, onabotulinumtoxinA (BT-A) and anti-CGRP mAbs may be used together, and some pre-clinical and clinical evidence of an additive action of the 2 drugs is emerging. In particular, since BT-A acts mainly on C-fibers and anti-CGRP mAbs on Aδ ones, their association may prevent the wearing-off phenomenon of BT-A, thus giving an additional benefit in those patients experiencing an incomplete response to BT-A alone. Despite this, the clinical studies available in the literature have a small sample size, often a retrospective design, and are heterogeneous in terms of the outcomes chosen. Considering this, the evidence of a favorable effect of the association between BT-A and anti-CGRP mAbs is still scarce. Furthermore, this association is explicitly forbidden by many National regulatory agencies, due to the high costs of both treatments. Anyway, their association could help in reducing the burden associated with the most severe cases of CM, thus relieving the direct and indirect costs of this condition. More well-designed studies with big samples are needed to unveil the real therapeutic gain of this association. Moreover, pharmacoeconomics studies should be performed, to assess the economic suitability of this association.