CGRP monoclonal antibodies improve benefit of onabotulinumtoxinA in patients with migraine

Patients with migraine who took calcitonin gene-related peptide-targeted monoclonal antibody therapy in combination with onabotulinumtoxinA had fewer monthly headache days and less migraine-related disability, according to researchers.

“The reason that we did this analysis is that migraine is a complex disease and in many patients, particularly those who have chronic migraine, the use of a monotherapeutic approach may not be successful,” Andrew M. Blumenfeld, MD, director of the Headache Center of Southern California, said during a presentation at the American Headache Society (AHS) virtual meeting. “Combination treatments may be needed, but we have very little data available to us on what happens when we combine treatments.”

Benefits of combination therapy

Blumenfeld and colleagues conducted a retrospective, longitudinal chart review of 245 adults with chronic migraine who were treated with onabotulinumtoxinA for two or more consecutive cycles, and then subsequently received treatment with onabotulinumtoxinA plus calcitonin gene-related peptide-targeted (CGRP) monoclonal antibody therapy for 1 or more months. The CGRP monoclonal antibodies included in the study were Aimovig (erenumab; Amgen, Novartis), Emgality (galcanezumab, Eli Lilly and Co.) and Ajovy (fremanezumab-vfrm, Teva).

Combination therapy was associated with a mean reduction in monthly headache days of 1.8 days at 3 months, 3.8 days at 6 months, 3.5 days at 9 months and 4 days at 12 months. The proportion of patients with a reduction of 50% or more in the number of monthly headache days was 25.7% at 3 months, 36.7% at 6 months, 33.3% at 9 months and 31.5% at 12 months.

After starting combination therapy, patients also had mean reductions from baseline in Migraine Disability Assessment Scale (MIDAS) scores of 6.3 points at 3 months, 11.1 points at 6 months, 6.1 points at 9 months and 8.4 points at 12 months. The proportion of patients with a reduction in MIDAS scores of five or more points was 36% at 3 months, 45.1% at 6 months, 43.7% at 9 months and 44.8% at 12 months.

Among the study population with one or more follow-up visits, 25.3% discontinued treatment; more participants discontinued CGRP monoclonal antibodies vs. onabotulinumtoxinA (23.3% vs. 3.3%). The most common adverse events among the entire study population were constipation (27.8%) and nausea (8.6%).

Results of subgroup analysis

Researchers conducted a sensitivity analysis to evaluate the efficacy of combination therapy in a subset of 172 adults (82.6% women; mean age, 49.9 years) who met treatment criteria outlined in an AHS position statement. According to the researchers, the AHS position statement advises that the combination of therapies “may be appropriate for” adults who have 4 to 7 monthly headache days with moderate migraine-related disability, 8 to 14 monthly headache days with any level of disability or for patients who have 15 or more monthly headache days for whom two quarterly injections of onabotulinumtoxinA is ineffective or intolerable.

Participants in the subgroup analysis had an average of 21 monthly headache days before beginning onabotulinumtoxinA and an average of 13 monthly headache days before adding CGRP monoclonal antibodies. At baseline, the mean MIDAS scale score was 52.

Patients in the subgroup analysis who received both treatments had mean decreases in the number of monthly headache days of 2.2 days at 3 months, 3.9 days at 6 months and 4.3 days at 9 months and at 12 months. Patients’ MIDAS scores decreased by a mean of 8.5 points at 3 months, 13.7 points at 6 months, 8.4 points at 9 months and 10.5 points at 12 months.

Among the subgroup, 25.5% discontinued treatment; more patients discontinued the CGRP monoclonal antibody vs. onabotulinumtoxinA (24.2% vs. 3%), according to the researchers. The most common adverse events were constipation (9.7%) and nausea (7%). Overall, 27.3% of patients reported adverse events.

Blumenfeld said that more research is needed to further assess the benefits, but the reduction in the number of headache days “suggests that there is at least an additive benefit, but there is also the possibility of a synergistic benefit from this combination.”

“This retrospective chart analysis was one of the first datasets to analyze this combination and is positive because not only does it show an efficacy trend, but it also shows us that there are no major issues with safety and tolerability,” he said.

References:

• Blumenfeld AM, et al. Real-world evidence for control of patients with chronic migraine who received calcitonin gene-related peptide monoclonal antibody therapy added to onabotulinumtoxinA treatment. Presented at: American Headache Society Virtual Meeting; June 3-6, 2021.
• Blumenfeld AM, et al. Real-world evidence for control of chronic migraine in patients meeting American Headache Society criteria who received calcitonin gene-related peptide monoclonal antibody therapy added to onabotulinumtoxinA treatment. Presented at: American Headache Society Virtual Meeting; June 3-6, 2021.