ConexiantCGRP Therapies May Reduce Migraine Days

Researchers applied GRADE certainty assessments to pooled data from 14,725 chronic migraine patients across RCTs identified through October 2025. High-certainty evidence supported eptinezumab, erenumab, fremanezumab, galcanezumab, and atogepant for monthly migraine day reduction; a head-to-head comparison favored erenumab over topiramate on both efficacy and tolerability. Most CGRP trials were industry-funded with a median follow-up of only 12 weeks.

Clinical Considerations

• High-certainty evidence: eptinezumab, erenumab, fremanezumab, galcanezumab, and atogepant each reduced monthly migraine days by approximately 2 days versus placebo
• Fremanezumab and erenumab showed high-certainty evidence for 50% responder outcomes; eptinezumab evidence was low certainty due to unexplained heterogeneity
• Rimegepant showed little to no effect on monthly migraine days in mixed chronic/episodic populations across 2 trials
• Tolerability signals: erenumab and atogepant probably increased constipation; atogepant probably also increased nausea; galcanezumab was the only agent associated with reduced all-cause dropout
• Botulinum toxin showed low-certainty modest benefit; propranolol, topiramate, valproate, and fluoxetine evidence was limited by small, high-risk-of-bias trials
• Long-term safety and durability data remain limited; independent head-to-head trials are absent

Practice Applications

• Consider CGRP-targeted monoclonal antibodies and gepants as first-line preventive options for chronic migraine given high-certainty efficacy evidence
• Recognize erenumab’s high-certainty superiority over topiramate in efficacy and tolerability as a clinically meaningful differentiator when counseling patients on preventive options
• Monitor constipation and nausea in patients initiating erenumab or atogepant, particularly those with baseline GI comorbidities
• Avoid drawing long-term safety conclusions from current trial data; median follow-up of 12 weeks does not support durability claims