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Retreating migraine patients in the second year with monoclonal antibodies anti-CGRP pathway: the multicenter prospective cohort RE-DO study

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Abstract

Background

The outcome of migraine patients retreated with monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (anti-CGRP) or its receptor (anti-CGRPr) is not completely known.

Methods

This multicentric prospective observational cohort study assessed monthly migraine days (MMDs), migraine acute medication intake (MAMI), and HIT-6 at baseline, after 90–112 days (Rev-1), after 84–90 days since Rev-1 (Rev-2) and 30 days after the last injection of anti-CGRP/CGRPr mAbs (Year-end), in the first and the second year after a discontinuation period.

Results

We enrolled 226 patients (79.6% with chronic migraine; 55.3% on erenumab and 44.7% on galcanezumab or fremanezumab). MMDs, MAMI, and HIT-6—did not differ at the respective first and second-year evaluations in the entire cohort, and comparing anti-CGRP with anti-CGRPr Abs. MMDs (18.1 ± 7.8 vs. 3.4 ± 7.8), MAMI (26.7 ± 28.3 vs.17.7 ± 17.2), and HIT-6 scores (63.1 ± 5.9 vs. 67.1 ± 10.3) were lower in the second year than in the pre-treatment baseline (consistently, p < 0.0001). Second-year baseline MMDs were lower in patients on anti-CGRP mAbs (p = 0.001) and with lower pre-treatment baseline MMDs (p ≤ 0.001).

Conclusion

Anti-CGRP/CGRPr mAbs are effective in the second as in the first year. The use of anti-CGRP or CGRPr mAbs influenced the second-year baseline MMDs, but their effectiveness did not differ during the two treatment years.

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Data availability

Anonymized data will be shared by request from any qualified investigator..

Abbreviations

AIFA:

Agenzia Italiana del Farmaco (Italian Medicines Agency)

CGRP:

Calcitonin gene-related peptide

CGRPr:

Calcitonin gene-related peptide receptor

CI:

Confidence intervals

CM:

Chronic migraine

EM:

Episodic migraine

HFEM:

High frequency episodic migraine

HIT-6:

Headache Impact Test 6 items

mAb:

Monoclonal antibody

MAMI:

Monthly Acute Medications Intake

MIDAS:

Migraine Disability Assessment

MMDs:

Monthly migraine days

MO:

Medication overuse

NRS:

Numerical Rating Scale

OR:

Odds ratio

RCT:

Randomized controlled trials

RR:

Response rate

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Funding

The study costs were covered by Fondazione Policlinico Campus Bio-Medico.

Author information

Authors and Affiliations

  1. Unità Cefalee e Neurosonologia, Fondazione Policlinico Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128, Rome, Italy

    Fabrizio Vernieri, Nicoletta Brunelli & Claudia Altamura

  2. Neurologia, Dipartimento di Medicina e Chirurgia, Università Campus Bio-Medico di Roma, Rome, Italy

    Fabrizio Vernieri, Sergio Soeren Rossi & Claudia Altamura

  3. Digital and Predictive Medicine, Pharmacology and Clinical Metabolic Toxicology, Headache Center and Drug Abuse, Laboratory of Clinical Pharmacology and Pharmacogenomics, Department of Specialist Medicines, AOU Policlinico di Modena, Modena, Italy

    Simona Guerzoni & Carlo Baraldi

  4. Headache Center, Section of Clinical Pharmacology and Oncology, Department of Health Sciences, Careggi University Hospital, University of Florence, Florence, Italy

    Luigi Francesco Iannone & Pierangelo Geppetti

  5. Headache Center, ASST Spedali Civili of Brescia, Department Continuity of Care and Fragility, Department of Clinical and Experimental Sciences, Neurological Clinic, University of Brescia, Brescia, Italy

    Renata Rao & Francesca Schiano di Cola

  6. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy

    Raffaele Ornello, Valentina Taranta & Simona Sacco

  7. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy

    Sabina Cevoli

  8. Headache Center, Neurology Unit, L. Sacco University Hospital, Milan, Italy

    Carlo Lovati

  9. Neurology Unit, Headache Center, Tor Vergata University Hospital, Rome, Italy

    Maria Albanese

  10. Department of Systems Medicine, Tor Vergata University, Rome, Italy

    Maria Albanese

  11. IRCCS Neuromed, Pozzilli, Isernia, Italy

    Armando Perrotta

  12. Neuroimaging Research Unit, Division of Neuroscience; Neurology Unit and Neurophysiology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy

    Ilaria Cetta & Massimo Filippi

  13. Vita-Salute San Raffaele University, Milan, Italy

    Ilaria Cetta & Massimo Filippi

Authors
  1. Fabrizio Vernieri
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  2. Nicoletta Brunelli
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  3. Simona Guerzoni
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  4. Luigi Francesco Iannone
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  6. Renata Rao
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  7. Francesca Schiano di Cola
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  8. Raffaele Ornello
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  9. Sabina Cevoli
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  10. Carlo Lovati
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  11. Maria Albanese
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  13. Ilaria Cetta
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  14. Sergio Soeren Rossi
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  15. Valentina Taranta
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  16. Massimo Filippi
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  17. Pierangelo Geppetti
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  18. Simona Sacco
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  19. Claudia Altamura
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Corresponding author

Correspondence to Fabrizio Vernieri.

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Conflict of interest

Fabrizio Vernieri received travel grants, honoraria for advisory boards, speaker panels, or clinical investigation studies from Allergan/Abbvie, Amgen, Angelini, Lilly, Lundbeck, Novartis, and Teva. Simona Guerzoni received honoraria and fees from Allergan/Abbvie, Lilly, Lundbeck, Teva, Novartis and Pfizer. Luigi Francesco Iannone received personal fees from Lilly and Teva and travel grants from Lundbeck. Carlo Baraldi received honoraria and fees from Allergan, Lilly, Lundbeck, Teva and Novartis. Renata Rao received honoraria for travel grants, honoraria for advisory boards, speaker panels from Novartis, Lillly, Teva, Allergan, Lundbeck. Francesca Schiano di Cola received speaker honoraria from Lilly, Lundbeck and Novartis. Sabina Cevoli received travel grants, honoraria for advisory boards, speaker panels or clinical investigation studies from Novartis, Teva, Lilly, Allergan, Ibsa, Amgen and Lundbeck. Raffaele Ornello reports speaker fees from Novartis and Lilly, travel grants from Teva, and support for publication from Novartis and Allergan. Carlo Lovati received grants from Novartis and Lilly. Maria Albanese has been a consultant and member of Advisory Board for Novartis, Teva, Lundbeck, Lilly, Allergan/Abbvie; has received funding for travel and speaker honoraria from Lusofarmaco, Angelini, Novartis, Lilly, Teva, Merck-Serono. Armando Perrotta received travel grants, honoraria for advisory boards, speaker panels, or clinical investigation studies from Allergan, Lilly, Novartis, and Teva. Ilaria Cetta reports personal fees from Lilly for speaker activities. Massimo Filippi is Editor-in-Chief of the Journal of Neurology and Associate Editor of Neurological Sciences, received compensation for consulting services and/or speaking activities from Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries; and receives research support from Biogen Idec, Merck-Serono, Novartis, Teva Pharmaceutical Industries, Roche, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Pierangelo Geppetti received personal fees from Allergan, Lilly, Novartis, Amgen, TEVA; grants from Amgen, TEVA, Eli-Lilly, Allergan, Chiesi; Scientific Advisory Board, Endosome Therapeutics; Founding scientist of FloNext srl, Spinoff of the University of Florence. Simona Sacco reports personal fees from Allergan-AbbVie, AstraZeneca, Abbott, Teva, Novartis, Novo Nordisk, Medscape, Neurodiem and Eli Lilly. Claudia Altamura received travel grants and honoraria from Novartis, Lilly, Lusofarmaco, Laborest, Abbvie-Allergan, Almirall. Nicoletta Brunelli, Sergio Soeren Rossi and Valentina Taranta have nothing to disclose.

Ethical standard statement

The study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. Informed consent was obtained from patients for collecting anonymously clinical and demographics data.

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Vernieri, F., Brunelli, N., Guerzoni, S. et al. Retreating migraine patients in the second year with monoclonal antibodies anti-CGRP pathway: the multicenter prospective cohort RE-DO study. J Neurol 270, 5436–5448 (2023). https://doi.org/10.1007/s00415-023-11872-2

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