If Ajovy (fremanezumab) is stopped, will my migraines return?

Will Migraines Return After Stopping Ajovy?

Yes, migraines will return after stopping Ajovy (fremanezumab), though they typically remain less severe than before treatment started. The evidence consistently shows that migraine frequency increases within weeks to months of discontinuation, but patients generally maintain some residual benefit compared to their pre-treatment baseline 1, 2.

What Happens When You Stop Ajovy

Timeline of Migraine Return

When fremanezumab is discontinued after successful treatment:

• Within 3 months: Monthly migraine days increase by approximately 4.4 days compared to the end of active treatment 2
• Sustained partial benefit: Despite worsening, patients still experience about 3.8 fewer monthly migraine days compared to their original pre-treatment baseline 2
• Response rate decline: The proportion of patients maintaining ≥50% reduction in migraine frequency drops significantly (by 58%) after stopping treatment 2

Real-World Evidence from Long-Term Studies

The most compelling data comes from a 2025 Greek prospective study that mandatorily paused fremanezumab after 24 months of continuous treatment 1. This study revealed critical patterns:

• Migraines relapsed in all previous responders during the treatment pause
• Upon restarting fremanezumab, the medication was less effective than before discontinuation
• 31% of chronic migraine patients who previously responded failed to achieve ≥50% reduction after restarting (compared to only 9.7% of episodic migraine patients) 1
• The rate of "super-responders" (≥75% reduction) also dropped significantly after treatment interruption 1

Key Clinical Considerations

Chronic vs. Episodic Migraine

Patients with chronic migraine experience more pronounced worsening after discontinuation:

• Chronic migraine patients showed sustained reductions of 6.5 monthly migraine days from baseline even after stopping, but this represents significant deterioration from their on-treatment state 2
• Episodic migraine patients may fare somewhat better, with smaller increases in migraine frequency after cessation 1

Medication Overuse Patterns

After stopping Ajovy:

• Acute headache medication use increases by approximately 3.2 days per month 2
• Monthly acute medication days still remain about 1.7 days lower than original baseline 2

Critical Pitfall: Treatment Interruption

The evidence strongly suggests that mandated treatment pauses may be counterproductive 1. When patients stop and restart fremanezumab:

• Re-initiation may not restore the same level of efficacy achieved during initial continuous treatment
• This reduced effectiveness is particularly pronounced in the first 3 months after restarting
• The biological mechanism remains unclear, but may involve changes in CGRP pathway regulation

CGRP Levels After Discontinuation

Research shows that free CGRP plasma concentrations do not change significantly after stopping fremanezumab, returning to levels similar to untreated migraine patients within 16 weeks 3. This suggests the return of migraines is related to loss of therapeutic CGRP blockade rather than rebound elevation.

Practical Management Approach

For patients considering discontinuation:

1. Expect gradual worsening over 1-3 months after the last injection
2. Monitor closely for return of migraine frequency and severity
3. Have acute treatment strategies ready as medication use will likely increase
4. Consider continuation if treatment is effective and well-tolerated, rather than arbitrary treatment pauses
5. If restarting is necessary, recognize that it may take time to re-establish previous efficacy levels, particularly in chronic migraine

When Discontinuation May Be Reasonable

Based on real-world data, approximately 26% of patients achieved such substantial improvement that discontinuation was appropriate after 2 years of treatment 4. However, this represents a minority of patients, and the decision should be based on sustained, substantial improvement rather than arbitrary time limits.

The evidence does not support routine mandatory treatment pauses in patients who are responding well to fremanezumab 1. Continuation of effective therapy appears preferable to risking loss of disease control and potentially reduced efficacy upon restarting.