Objective:

To further evaluate if the response to anti-CGRP monoclonal antibodies (mAbs) is enhanced with concurrent onabotulinumtoxinA treatment with regard to monthly migraine days (MMD) in patients with chronic migraine. 

Background:

Chronic migraine is associated with impairment in quality of life, increased medical and psychiatric comorbidities, and accounts for significant health resource utilization. Many patients with chronic migraine do not achieve clinically meaningful improvement in their headache frequency and intensity with monotherapy. Therefore, the immense burden associated with chronic migraine calls for a multifaceted treatment approach targeting multiple aspects of migraine pathophysiology in hopes to improve patient outcomes. OnabotulinumtoxinA has been demonstrated to selectively inhibit unmyelinated C-fibers but not Aδ-meningeal nociceptors. Fremanezumab, an anti-CGRP monoclonal antibody, has been shown to prevent the activation of Aδ-fibers but not C-fibers. Therefore, concurrent use of anti-CGRP with onabotulinumtoxinA may have a synergistic effect with targeting both Aδ-fibers and C-fibers. 

Design/Methods:

The electronic medical records of patients concurrently treated with anti-CGRP mAbs and onabotulinumtoxinA were extracted (n=121). The cohort’s (92.56% female, 51.19 ± 13.59 years old, 28.13 ± 4.04 baseline MMD) MMD were examined at baseline, before and after monotherapy of anti-CGRP mAb and onabotulinumtoxinA, and following combined treatment for at least 2 sets of onabotulinumtoxinA injections. The reduction of MMD for each treatment group were compared with the Kruskal-Wallis and Dunn’s comparison tests. 

Results:

Anti-CGRP mAb alone reduced an average of 13.51 ± 6.47 migraine days per month, a non-significant difference (p>0.99) from the 13.25 ± 7.35 MMD reduced from onabotulinumtoxinA treatment. Concurrent treatment of both anti-CGRP mAb and onabotulinumtoxinA resulted in an average reduction of 22.61 ± 5.62 MMD from baseline. The reduction from the monotherapies were significantly different from the dual therapy (p>0.0001). 

Conclusions:

Combination therapy of anti-CGRP monoclonal antibodies and onabotulinumtoxinA may be more efficacious than monotherapy, possibly due to their synergistic mechanisms of action.