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Study breakdown

Combining Anti-CGRP Antibodies With Botox Nearly Doubles Chronic Migraine Relief

CohortModerate evidence
The takeaway

Dual therapy with anti-CGRP antibodies and onabotulinumtoxinA reduced chronic migraine days from 30 to 8 per month, with 68% of patients achieving at least 50% improvement.

30→8 migraine days

Dual therapy with anti-CGRP antibodies and Botox reduced monthly migraine days from 30 to 8, with nearly half of patients achieving 75% or greater improvement

What the researchers found

Dual therapy reduced median monthly migraine days from 30 to 15 after the first treatment, then further to 8 after adding the second (p < 0.0001 for both reductions). Among 194 dual-therapy patients, 68% achieved ≥50% reduction and 46.4% achieved ≥75% reduction in monthly migraine days. Consecutive monotherapy reduced migraine days less effectively: onabot alone to 15, anti-CGRP alone to 12. Only 16.6-19.7% of monotherapy patients achieved ≥75% reduction. Dual therapy was significantly better than either monotherapy (p < 0.0001).

Why it matters

Most chronic migraine patients don't get adequate relief from a single treatment. Anti-CGRP antibodies and Botox target different aspects of migraine biology — CGRP blocks the pain signal peptide, while Botox reduces peripheral sensitization. This study provides real-world evidence that combining them works better than either alone, from median 30 to 8 migraine days per month.

The numbers in context

Median monthly migraine days measured during monotherapy periods versus combination therapy periods.

How the study worked

Retrospective cohort study using Cleveland Clinic electronic medical records from June 2018 to November 2021. Compared 194 concurrent dual-therapy patients with 229 consecutive monotherapy patients. Monthly migraine days tracked at baseline, after first therapy, and after 3 months of dual therapy.

Who was studied

Chronic migraine patients receiving combination CGRP mAb and onabotulinumtoxinA

What this study cannot tell us

Retrospective study without randomization — patients who received dual therapy may differ from monotherapy patients. No blinding or placebo control. Cleveland Clinic population may not represent all migraine patients. Self-reported migraine days subject to recall bias. Insurance and access factors may have influenced who received dual therapy.

How to read the evidence

Rated moderate: large real-world cohort study from a major academic center, but retrospective and non-randomized.

When this study was published

Published in 2024 with data from 2018-2021. Reflects the period when anti-CGRP antibodies first became widely available for combination use.

The bigger picture

This supports a multimodal approach to chronic migraine, combining a peptide-targeting antibody with a neurotoxin that work through different mechanisms. The synergy validates the concept that migraine has multiple biological drivers that benefit from simultaneous targeting.

Questions still open

  • Would a randomized controlled trial confirm the synergy between anti-CGRP and Botox?
  • Which anti-CGRP antibody works best in combination with Botox?
  • Is dual therapy cost-effective compared to optimizing monotherapy?

Common questions

Can you take a CGRP antibody and Botox together for migraines?
Yes — this study found that combining them reduced chronic migraine days from 30 to 8 per month, significantly better than either alone. Nearly half of patients improved by 75% or more.
Why would two migraine treatments work better together?
Anti-CGRP antibodies block the pain-signaling peptide CGRP, while Botox reduces nerve sensitization in the head and neck. They target different parts of migraine biology, so combining them attacks the problem from two angles.

Read the original research

Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.

CNS drugs, 38(6), 481-491

Citation

Salim, Amira; Hennessy, Elise; Sonneborn, Claire; Hogue, Olivia; Biswas, Sudipa; Mays, MaryAnn; Suneja, Aarushi; Ahmed, Zubair; Mata, Ignacio F. (2024). Synergism of Anti-CGRP Monoclonal Antibodies and OnabotulinumtoxinA in the Treatment of Chronic Migraine: A Real-World Retrospective Chart Review.. CNS drugs, 38(6), 481-491. https://doi.org/10.1007/s40263-024-01086-z