Additive Interaction Between Onabotulinumtoxin-A and Erenumab in Patients With Refractory Migraine

Abstract

In the last decade, notable progresses have been observed in chronic migraine preventive treatments. According to the European Headache Federation and national provisions, onabotulinumtoxin-A (BTX-A) and monoclonal antibodies acting on the pathway of calcitonin gene–related peptide (CGRP-mAbs) should not be administered in combination due to supposed superimposable mechanism of action and high costs. On the other hand, preclinical observations demonstrated that these therapeutic classes, although operating directly or indirectly on the CGRP pathway, act on different fibers. Specifically, the CGRP-mAbs prevent the activation of the Aδ-fibers, whereas BTX-A acts on C-fibers. Therefore, it can be argued that a combined therapy may provide an additive or synergistic effect on the trigeminal nociceptive pathway. In the present study, we report a case series of 10 patients with chronic migraine who experienced significant benefits with the combination of both erenumab and BTX-A compared to each therapeutic strategy alone. A reduction in frequency and intensity of headache attacks (although not statistically significant probably due to the low sample size) was observed in migraine patients treated with a combined therapy with BTX-A and erenumab compared to both BTX-A and erenumab alone. Moreover, the combined therapy with BTX-A and erenumab resulted in a statistically significant reduction in the symptomatic drug intake and in migraine-related disability probably related to a reduced necessity or also to a better responsiveness to rescue treatments. Present data suggest a remodulation of current provisions depriving patients of an effective therapeutic strategy in peculiar migraine endophenotypes.

Efficacy and tolerability of combination treatment of topiramate and greater occipital nerve block versus topiramate monotherapy for the preventive treatment of chronic migraine: A randomized controlled trial

“…A recent retrospective study showed additive effects of OBT-A and CGRP mAbs in CM (22). Similar beneficial results have been reported in 10 refractory CM patients with the combination of both erenumab and OBT-A compared to each therapeutic strategy alone (23). Thus, there is emerging evidence that proper combination treatment in CM may provide additional benefits although the cost may become prohibitive.…”

Reducing the Burden of Migraine: Safety and Efficacy of CGRP Pathway-Targeted Preventive Treatments

“…Average monthly headache frequency was reduced by 9.3 days following at least 2 cycles of onabotulinumtoxinA, and then a further 3.5 to 4.0 days over 6 to 12 months after the addition of a CGRP monoclonal antibody, along with accompanying clinically meaningful improvements in migraine-related disability; no new safety concerns were identified [ 90 ]. The evidence from this study supports similar findings from previous chart reviews in smaller cohorts of patients that suggested benefits from combination therapy, including reduced headache frequency, disability, and acute headache medication use [ 91 , 92 , 93 ]. While these studies looked at the effects of adding a CGRP monoclonal antibody to an existing onabotulinumtoxinA regimen, it would also be of interest to investigate the effectiveness of adding onabotulinumtoxinA therapy to CGRP monoclonal antibody treatment compared with switching therapies.…”

Migraine Prevention with Erenumab: Focus on Patient Selection, Perspectives and Outcomes

“…A recent consensus suggests the combination of onabotulinumtoxinA with anti-CGRP mAbs as a possible therapeutic strategy in patients with refractory migraine or a suboptimal response to the single treatment. 94 Some case series proved the efficacy of this combined treatment in reducing MHDs/MMDs 95 , 96 and headache severity 97 with no safety concerns thanks to the optimal tolerability and safety profiles of the treatments. 95–98 Both the treatments act on the CGRP pathway: mAbs inhibit CGRP binding to its receptor on Aδ-fibers, onabotulinumtoxinA exerts its action on C-type fiber with still unknown mechanisms; thus, their concomitant use might enhance the blockade of the pathway.…”