OnabotulinumtoxinA Add-On to Monoclonal Anti-CGRP Antibodies in Treatment-Refractory Chronic Migraine

Abstract

We sought to assess the effectiveness of combining dual therapy with onabotulinumtoxinA (BTX) add-on to anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (anti-CGRP MAbs) in treatment-refractory patients with chronic migraine (CM). We retrospectively reviewed the medical files of 19 treatment-refractory patients with CM who had failed to two oral migraine preventatives, at least three consecutive BTX cycles (less than 30% response rate), at least three consecutive sessions with either fremanezumab or erenumab (less than 30% response rate), and were eventually switched to dual therapy with BTX add-on to any of the already-given anti-CGRP MAbs. We then assessed from baseline to each monotherapy or dual intervention predefined efficacy follow-up the changes in the following efficacy outcomes: (i) monthly headache days (MHD), (ii) monthly days with moderate/severe peak headache intensity, and (iii) monthly days with intake of any acute headache medication. Response (50% reduction in MHD) rates, safety, and tolerability were also determined. In the majority of cases (n = 14), dual targeting proved effective and was associated with clinically meaningful improvement in all efficacy variables; 50% response rates (also disability and QOL outcomes) coupled with favorable safety/tolerability. Our results advocate in favor of the view that dual therapy is effective and should be considered in difficult-to-treat CM patients who have failed all available monotherapies.

Efficacy and safety of fremanezumab for migraine prophylaxis in patients with at least three previous preventive failures: Prospective, multicenter, real‐world data from a Greek registry

“…In patients failing to achieve at least a 30% reduction in mean MHD after 6 months of fremanezumab treatment, dual targeting with onabotulinumtoxinA add‐on to fremanezumab might be the optimal approach, based on available efficacy results [25, 26], as further exposure to fremanezumab monotherapy is unlikely to produce a delayed clinically meaningful response. An additive effect of onabotulinumtoxinA add‐on to fremanezumab might provide the mechanistic rationale for this dual therapy approach having a distinct mechanism of action when either therapy is given as monotherapy; onabotulinumtoxinA by inhibiting the activation and sensitization of unmyelinated neuronal C‐wide dynamic range afferents [27] and fremanezumab by selectively inhibiting sustained firing of Aδ‐HT fibers in the trigeminal ganglion [7, 28].…”

Quantitative and Qualitative Pain Evaluation in Response to OnabotulinumtoxinA for Chronic Migraine: An Observational Real-Life Study

“…An increasing number of reports propose for hard-to-treat patients a combined strategy of OBT-A and monoclonal antibodies targeting the CGRP pathway [41][42][43] based on the fact that they play synergistic effects within the trigeminovascular system, with monoclonal antibodies inhibiting the activation of Aδ fibers and OBT-A that of C fibers [44]. These two types of fibers have a key role in pain perception along the trigeminal pathway.…”

Real-World Use of Ubrogepant as Acute Treatment for Migraine with an Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody: Results from COURAGE

“…Some individuals with migraine also need a preventive treatment to reduce the frequency, severity, and duration of attacks and avoid escalating acute treatment use. In clinical practice, health care providers have successfully used onabotulinumtoxinA and anti-CGRP mAbs in people with migraine [ 24 ]; however, there are a number of practical and hypothetical reasons that suggest that the combination of ubrogepant and an anti-CGRP mAb would be an effective paradigm to maximize outcomes. First, anti-CGRP mAbs have demonstrated efficacy in the preventive treatment of migraine; however, they are administered monthly or quarterly, and people have reported wearing-off of effectiveness towards the end of a treatment cycle [ 25 ].…”