The Effect of Adding Calcitonin Gene‐Related Peptide Monoclonal Antibodies to Onabotulinum Toxin A Therapy on Headache Burden: A Retrospective Observational Case Series

Background The calcitonin gene-related peptide monoclonal antibody medications represent a novel and effective group of treatment options that can be added on to existing regimens such as onabotulinum toxin A injections for the treatment of refractory chronic migraine. Mechanistically, calcitonin gene-related peptide antibodies have been shown to inhibit Aδ fibers while onabotulinum toxin A modulates C fibers. Due to the differing loci of effect and anecdotal observations, a synergistic effect between these therapies is a theoretical possibility. The aim of this study was to investigate this relationship. Methods Patients from the University of Utah Headache Clinic having received at least two rounds of injections of onabotulinum toxin A who responded partially but not completely to therapy were started on a calcitonin gene-related peptide antibody medication. The patients’ responses to a brief headache burden questionnaire prior to their onabotulinum toxin A administration at the time of each visit were collected. Parameters we monitored included the number of headaches experienced while receiving onabotulinum toxin A therapy, the initial timing of the of the wear off period, and the number of headaches after that the wear off period began. Results Half of the 36 patients included in the study demonstrated an improvement in their headache burden based on at least one parameter from their questionnaire. These 18 patients reported an average increase of 2.0 additional weeks for the beneficial effects of the onabotulinum toxin A to wear off. Twelve patients reported no change in onabotulinum toxin A efficacy while 6 patients showed greater headache burden or lower onabotulinum toxin A treatment efficacy following the initiation of one of the monoclonal antibodies. Conclusions Our study highlights the potential of calcitonin gene-related peptide monoclonal antibodies to serve as an effective add-on therapy for chronic migraine patients receiving onabotulinum toxin A injections, especially those designated “responders” but still experiencing the drug wear off prior to the next round of injections. Larger sample sizes and more frequent at-home questionnaire data are needed to corroborate these results.