Human Monoclonal Antibodies, BoNT-A Reduce Monthly Migraine Days in CM

BoNT-A and mABs that target CGRP receptor are beneficial in reducing monthly migraine days in patients with chronic migraine and medication overuse headache.

Human monoclonal antibodies (mABs) and botulinum toxin type A (BoNT-A) are associated with reductions in migraine symptoms in patients with chronic migraine and medication overuse headache, according to findings from a systematic review and meta-analysis published in Cephalalgia.

Migraine is the second largest contributor to disability-adjusted life years. As such, reducing its burden is an important public health priority.

Researchers from NorHEAD-Norweigian Center for Headache Research searched publication databases through May 2022 for studies evaluating topiramate, BoNT-A, or mABs targeting calcitonin gene-related peptide (CGRP) or its receptor for the treatment of chronic migraine with medication overuse headache. The primary outcome was a reduction in monthly migraine days by 50% or more.

A total of 10 reports from 9 unique studies published between 2006 and 2021 were included in this analysis. The studies compared mABs (n=4), BoNT-A (n=3), or topiramate (n=2) with placebo.

[P]atients may benefit of treatment with mABs and probably also BoNTA without needing withdrawal before or during treatment.

The pooled study population comprised 3,121 patients (mean age, 41-49 years; 83.5% women).

All 4 studies of mABs reported favorable outcomes, and in the pooled analyses, mABs was superior to placebo for the outcomes of change in:

  • monthly migraine days (mean difference [MD], -2.68; 95% CI, -3.46 to -1.91; I2, 1.00%; P =0.00);
  • ³50% response rate (odds ratio [OR], 2.90; 95% CI, 2.23-3.78; I2, 6.67%; P =0.00); and
  • medication overuse status to no overuse (OR, 2.09; 95% CI, 1.64-2.67; I2, 0.00%; P =0.00).

The adverse event rates for mABs ranged between 43.3% and 68.3% and dropout rates between 1.5% and 2.5%. The most common reported adverse events included injection site reactions of pain, erythema, induration, and hemorrhage; nasopharyngitis, upper respiratory tract, sinusitis, and urinary tract infections; muscle spasm; back pain; and fatigue.

Compared with placebo, BoNT-A was associated with a reduction in migraine frequency from baseline (MD, -1.92; 95% CI, -2.68 to -1.16; I2, 0.00%; P =0.00). The primary endpoint was reached in 2 of the studies whereas the third study significantly favored placebo over BoNT-A. The combined effect for achieving the 50% or more reduction in monthly migraine days was not significant (OR, 1.56; 95% CI, 0.42-5.75; I2, 91.63%; P =.50).

The rates of adverse events associated with BoNT-A ranged between 28.5% and 56.3% and drop-out rates between 2.9% and 7.4%. The most common adverse events were injection site pain, injection site hematoma, and muscular weakness.

No meta-analysis was performed using data from the studies of topiramate. However, both studies reported significant effects compared with placebo. The rate of adverse events ranged between 30% and 75%, the most common of which were paresthesia, nausea, dizziness, dyspepsia, fatigue, anorexia, alterations to taste, and disturbance to attention.

Study limitations included the short duration used to defined medication overuse headache, the small number of studies, and the combination of differing treatment strategies and doses.

These data indicated that CGRP mABs and BoNT-A improved symptoms of migraine among individuals with chronic migraine and medication overuse headache. “[T]he present meta-analysis indicated that such patients may benefit of treatment with mABs and probably also BoNTA without needing withdrawal before or during treatment,” the researchers noted.

“High-quality randomized trials are required to evaluate the effect of topiramate in chronic migraine patients with medication overuse headache,” they concluded.


Giri S, Tronvik E, Linde M, Pedersen SA, Hagen K. Randomized controlled studies evaluating Topiramate, Botulinum toxin type A, and mABs targeting CGRP in patients with chronic migraine and medication overuse headache: a systematic review and meta-analysis. Cephalalgia. March 1, 2023. doi:10.1177/03331024231156922