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If One CGRP Antibody for Migraine Doesn't Work, Should You Try Another? The Evidence Is Still Thin

ReviewPreliminary evidence
The takeaway

Despite growing interest in switching between CGRP monoclonal antibodies after discontinuation, available evidence remains insufficient to determine whether this strategy is effective for migraine prevention.

~50% discontinuation rate

Approximately half of patients receiving CGRP monoclonal antibodies for migraine prevention are expected to discontinue therapy, making the switching question clinically urgent

What the researchers found

Available data is insufficient to determine the efficacy of switching between CGRP receptor monoclonal antibodies following discontinuation of initial therapy, according to expert review aligned with European Headache Federation guidelines.

Why it matters

With ~50% of CGRP antibody users discontinuing treatment, the question of whether to try a different CGRP antibody is extremely common in clinical practice. Clarifying what the evidence says — and doesn't say — helps patients and doctors make informed decisions rather than operating on assumptions.

The numbers in context

Approximately 50% of patients receiving CGRP antibodies discontinue therapy. Available switching data comes from small studies and case series.

How the study worked

Database search for 'CGRP monoclonal antibody switch OR CGRP monoclonal antibody switching' to identify all available data on switching efficacy after CGRP MoAb discontinuation.

Who was studied

Migraine patients who discontinued initial CGRP antibody therapy

What this study cannot tell us

Limited by the scarcity of available switching data — the review can only synthesize what exists. Expert opinion fills gaps where evidence is absent. The field is evolving rapidly, so conclusions may change as new studies are published.

How to read the evidence

Preliminary — the review concludes that available evidence is insufficient to determine switching efficacy, reflecting the scarcity of published data rather than negative results.

When this study was published

Published in 2024, reflecting the current state of a rapidly evolving field where CGRP antibodies have only been available since 2018.

The bigger picture

CGRP antibodies have revolutionized migraine prevention, but they don't work for everyone. The question of what to do after a first CGRP antibody fails is one of the biggest unanswered questions in headache medicine. Whether to switch antibodies, try a gepant, or pursue entirely different treatments remains a clinical judgment call rather than an evidence-based decision.

Questions still open

  • Do different CGRP antibody mechanisms (anti-CGRP vs. anti-CGRP receptor) make switching between them more or less likely to succeed?
  • Would switching to a gepant (oral CGRP blocker) be more effective than switching between injectable CGRP antibodies?
  • What patient characteristics predict success when switching CGRP-targeted therapies?

Common questions

If my CGRP injection didn't work, should I try a different one?
It's a reasonable question, but the honest answer is that we don't have enough evidence to know for sure. The different CGRP antibodies work in slightly different ways — some block the CGRP protein itself (Ajovy, Emgality) while one blocks its receptor (Aimovig) — so theoretically switching could help. But the data to prove this is limited. Your neurologist can help weigh this option against alternatives like oral gepants or other preventive medications.
What options do I have if CGRP antibodies don't work for my migraines?
Several options exist: oral gepants (rimegepant, atogepant) target the same CGRP pathway but differently; traditional preventives like beta-blockers, anticonvulsants, or antidepressants; Botox injections for chronic migraine; and neuromodulation devices. Your headache specialist can help determine the best next step based on your specific migraine pattern and treatment history.

Read the original research

Switching CGRP(r) MoAbs in migraine: what evidence?

Expert opinion on biological therapy, 24(5), 327-333

Citation

Wells-Gatnik, William David; Martelletti, Paolo. (2024). Switching CGRP(r) MoAbs in migraine: what evidence?. Expert opinion on biological therapy, 24(5), 327-333. https://doi.org/10.1080/14712598.2024.2354386