Botox vs CGRP Antibodies for Chronic Migraine Prevention: What Real-World Evidence Shows | Research

The takeaway

OnabotulinumtoxinA (Botox) has the strongest real-world evidence for chronic migraine prevention with up to 3 years of safety data, while newer CGRP antibodies show promise but lack long-term real-world data.

55 real-world studies
OnabotulinumtoxinA had 55 real-world studies with up to 3 years of safety data, vastly more than erenumab (6 studies, 6 months) or other CGRP antibodies (1 study, 12 months)

What the researchers found

Across real-world studies published between 2010 and 2020:

• OnabotulinumtoxinA: 55 studies with long-term data (>1 year, up to 3 years). Substantial evidence for reducing headache number/frequency, decreasing acute medication use, and improving well-being and daily activity.

• Erenumab (CGRP mAb): 6 studies with data up to 6 months. More limited evidence showing benefits for the same parameters.

• Multiple CGRP mAbs: 1 study with data up to 12 months. Single study suggesting reduced headache frequency and impact.

• Topiramate: 1 study with data up to 3 months. Single study suggesting decreased headache frequency.

OnabotulinumtoxinA was the only treatment with long-term safety data from real-world settings reporting treatment-related adverse events.

Why it matters

Chronic migraine affects millions of people and choosing the right preventive treatment requires understanding not just clinical trial results but how treatments perform in everyday clinical practice. This review highlights a critical reality: while CGRP antibodies generated excitement at launch, Botox had far more real-world evidence supporting its effectiveness and safety. This information is essential for shared decision-making between patients and providers.

How the study worked

Systematic literature review searching MEDLINE, Embase, and the Cochrane Library, supplemented by back-referencing and additional searches, for publications from January 2010 to February 2020. Studies were screened, data extracted, and quality assessed. Results were narratively synthesized. Search criteria included all preventive medications for chronic migraine in adults.

What this study cannot tell us

The search ended in February 2020, missing several years of rapidly accumulating CGRP antibody real-world data. The massive imbalance in available studies (55 for Botox vs 6 for erenumab) reflects time on market rather than relative effectiveness. The review did not include head-to-head real-world comparisons. Publication bias may favor positive Botox outcomes given its longer history. Quality of included real-world studies varied considerably.

How to read the evidence

This is a systematic literature review of real-world evidence studies, providing a strong synthesis of observational data. While real-world evidence complements clinical trial data, the underlying studies are non-randomized and vary in quality. The systematic search methodology and quality assessment strengthen the review's credibility.

When this study was published

Published in 2023 with a literature search ending February 2020. Since then, CGRP antibodies have accumulated substantial additional real-world evidence. The Botox findings remain highly relevant, but the comparative gap has likely narrowed.

The bigger picture

The chronic migraine treatment landscape has been transformed by two peptide-related innovations: onabotulinumtoxinA (a peptide toxin that blocks neurotransmitter release) and CGRP-targeting antibodies (that block the calcitonin gene-related peptide pathway). This review captures a transitional moment where Botox's decade of real-world experience dwarfed the CGRP antibodies' early data. Since 2020, CGRP antibodies have accumulated considerably more evidence, potentially shifting this balance.

Questions still open

How does the real-world evidence for CGRP antibodies look now that several more years of data have accumulated since this review's search cutoff?
Are there patient subgroups that respond better to onabotulinumtoxinA versus CGRP antibodies in real-world practice?
Could combining onabotulinumtoxinA with CGRP antibodies provide additional benefit for treatment-resistant chronic migraine?

Common questions

Is Botox or CGRP antibodies better for chronic migraine?

This review found that both are effective, but Botox (onabotulinumtoxinA) had far more real-world evidence at the time — 55 studies with up to 3 years of safety data, compared to only 6 studies for erenumab. The CGRP antibodies were newer and hadn't yet accumulated comparable long-term data. Since this review, more CGRP evidence has emerged, and many specialists now consider both to be strong options depending on patient preference and response.

How do these peptide-based treatments prevent migraines?

OnabotulinumtoxinA (Botox) is a peptide toxin that blocks the release of neurotransmitters involved in pain signaling. It's injected into specific head and neck muscles every 12 weeks. CGRP antibodies (erenumab, galcanezumab, fremanezumab) block calcitonin gene-related peptide, a key signaling molecule that drives migraine attacks. Both approaches use peptide biology to interrupt the migraine cascade at different points.

Read the original research

Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review.

Pain and therapy, 12(1), 251-274

View on PubMed ↗Publisher’s paper ↗

Citation

Blumenfeld, Andrew M; Kaur, Gavneet; Mahajan, Anadi; Shukla, Hemlata; Sommer, Katherine; Tung, Amy; Knievel, Kerry L. (2023). Effectiveness and Safety of Chronic Migraine Preventive Treatments: A Systematic Literature Review.. Pain and therapy, 12(1), 251-274. https://doi.org/10.1007/s40122-022-00452-3