Objective:

To evaluate the effectiveness of calcitonin gene-related peptide (CGRP) targeted therapies in reducing monthly migraine headache days specifically in patients with chronic migraine.

Key Findings:

• CGRP therapies reduced monthly migraine headache days by approximately 2 days compared to placebo.
• High-certainty evidence supports eptinezumab, erenumab, fremanezumab, galcanezumab, and atogepant for reducing migraine days.
• Fremanezumab and erenumab showed high-certainty evidence for achieving at least a 50% reduction in migraine days.
• Galcanemab likely reduced dropout rates compared to placebo, while erenumab and atogepant increased constipation and nausea risks.
• Botulinum toxin may reduce migraine days but has low evidence certainty and increased discontinuation due to adverse events.
• Rimegepant probably had little or no effect on monthly migraine headache days in mixed chronic and episodic populations.

Interpretation:

Most CGRP-targeted therapies are likely effective for chronic migraine prophylaxis, but further independent head-to-head trials and longer-term studies are needed to confirm long-term safety and efficacy.

Limitations:

• Most trials were industry funded, raising potential bias.
• Median follow-up was only 12 weeks, limiting long-term safety conclusions.
• Sparse comparative data prevented planned network meta-analysis.
• High risk of bias in older preventive therapies limits confidence in findings.

Conclusion:

CGRP-targeted therapies are probably effective for chronic migraine, but larger independent trials and longer-term studies are necessary.