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CGRP-Blocking Pill Atogepant Reduced Migraine Days by ~7 Per Month in Real-World Italian Study

evidence
The takeaway

Atogepant 60 mg daily reduced monthly migraine days by 6.9 on average over 12 weeks in real-world practice, with a 48.1% response rate and only 6.6% dropout — even in patients who had failed prior CGRP antibodies.

48.1% responder rate

Nearly half of patients achieved ≥50% reduction in monthly migraine days with atogepant 60 mg at 12 weeks

What the researchers found

In 106 patients (52.8% chronic migraine, 87.7% female, mean age 50.6):

- Monthly migraine days decreased by 6.9 (SD 9.7, p<0.001) from baseline to 12 weeks

- 50% response rate: 48.1% of patients achieved ≥50% reduction in migraine days

- Significant reductions in acute medication use, disability scores (MIDAS), allodynia (ASC-12), and treatment optimization (mTOQ-6)

- Quality of life improved (MSQ role-function restriction)

- Only 6.6% dropout (4 for lack of efficacy, 3 for adverse events)

- Prior failure on anti-CGRP monoclonal antibodies was NOT a negative prognostic factor in the regression analysis

Why it matters

Real-world data often differs from clinical trial results because real patients are more complex. This study confirms atogepant works well in everyday clinical practice, even in difficult-to-treat patients who have failed other CGRP-targeting therapies. This suggests the oral gepant works through a different enough mechanism to benefit patients who didn't respond to injectable antibodies.

How the study worked

Multicenter prospective observational cohort study (STAR study) across 10 Italian headache centers. 106 adult patients with clinical indication for atogepant 60 mg daily were assessed at baseline and 12 weeks using multiple validated migraine and disability questionnaires. Multiple regression analysis evaluated predictors of treatment response.

What this study cannot tell us

Observational study without a placebo control group, so some improvement may reflect placebo effect or regression to the mean. Relatively small sample (106 patients) and short follow-up (12 weeks). Single-country (Italy) population may not generalize globally. The study was not blinded.

How to read the evidence

This is a prospective observational real-world study — stronger than retrospective analyses but weaker than randomized controlled trials due to lack of blinding and placebo control. The multicenter design and validated outcome measures add rigor.

When this study was published

Published in 2025 in Cephalalgia, this is among the first real-world evidence studies for atogepant, which was more recently approved than the anti-CGRP antibodies.

The bigger picture

Atogepant is part of the gepant class — small-molecule CGRP receptor antagonists taken as daily pills. This real-world evidence adds to the growing body of data showing gepants can complement anti-CGRP monoclonal antibodies, offering an oral option for patients who prefer pills over injections or who haven't responded to antibody therapy.

Questions still open

  • Why does atogepant work in some patients who failed anti-CGRP monoclonal antibodies — is it the oral route, different receptor binding dynamics, or both?
  • Would longer treatment (beyond 12 weeks) show sustained or improved efficacy?
  • How does atogepant's real-world effectiveness compare to rimegepant, the other approved oral gepant?

Common questions

Can I try atogepant if CGRP antibody injections didn't work for me?
This study suggests yes — prior failure on anti-CGRP monoclonal antibodies was not a predictor of poor response to atogepant. Nearly half of all patients, including those with prior failures, achieved significant migraine reduction. Discuss with your neurologist.
How is atogepant different from anti-CGRP antibody injections?
Atogepant is a small-molecule pill taken daily that blocks the CGRP receptor, while antibodies like erenumab are monthly injections. Despite targeting the same CGRP pathway, they work at different scales and binding sites, which may explain why some patients respond to one but not the other.

Read the original research

Effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study).

Cephalalgia : an international journal of headache, 45(4), 3331024251335927

Citation

Vernieri, Fabrizio; Iannone, Luigi Francesco; Lo Castro, Flavia; Sebastianelli, Gabriele; De Santis, Federico; Corrado, Michele; Marcosano, Marilena; Ornello, Raffaele; Grazzi, Licia; Montisano, Danilo Antonio; De Cesaris, Francesco; Munafò, Antonio; Fofi, Luisa; Doretti, Alberto; Vaghi, Gloria; Pistoia, Francesca; Ferrandi, Delfina; Battistini, Stefania; Sacco, Simona; Guerzoni, Simona; Altamura, Claudia. (2025). Effectiveness and tolerability of atogepant in the prevention of migraine: A real life, prospective, multicentric study (the STAR study).. Cephalalgia : an international journal of headache, 45(4), 3331024251335927. https://doi.org/10.1177/03331024251335927