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Anti‑CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at two years

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Abstract

Background

Monoclonal antibodies targeting calcitonin gene-related peptide (anti-CGRP mAbs) have shown clinical effectiveness and safety in randomized clinical studies. However, long-term studies in clinical practice remain limited.

Aim

To assess the long-term effectiveness, clinical predictors and safety of three anti-CGRP mAbs (erenumab, galcanezumab, fremanezumab) in resistant migraine patients.

Method

A single-center retrospective study was conducted from December 2019 to June 2023 involving 120 resistant migraine patients who received at least a month of anti-CGRP mAbs treatment. Patients completed a headache diary that included monthly acute medication intake (MAM), monthly migraine days (MMD), adverse events as well as completed Patient-Reported Outcome questionnaires (MIDAS [Migraine Disability Assessment] and Headache Impact Test 6 [HIT-6]). The number of patients achieving a ≥ 50% reduction in monthly migraine days was determined and classified as ≥ 50% responders, and baseline parameters and logistic regression between responders and non-responders were analyzed to identify potential predictors of response. Adverse events were registered in every follow-up.

Results

Treatment with anti-CGRP mAbs led to reductions in MIDAS, HIT-6, MMD and MAM from baseline to 6–24 months. At 6–12 months, responders (61% and 57%, respectively) exhibited lower baseline MMD and MAM. Medication overuse  was associated with non-responders from 6 to 24 months and it was identified as a negative predictor of treatment effectiveness (OR 0.23, 95% CI 0.07–0.74; p = 0.014).

Conclusion

Anti-CGRP mAbs prove effectiveness and safety over a 24-month period in a RM population. Patients with no medication overuse and lower basal MMDs and MAM may respond better to anti-CGRP mAbs.

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References

  1. Matías-Guiu J, Porta-Etessam J, Mateos V, et al. One-year prevalence of migraine in Spain: a nationwide population-based survey. Cephalalgia. 2011;31(4):463–70. https://doi.org/10.1177/0333102410382794.

    Article  PubMed  Google Scholar 

  2. Stovner LJ, Nichols E, Steiner TJ, et al. Global, regional, and national burden of migraine and tension-type headache, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet Neurol. 2018;17(11):954–76. https://doi.org/10.1016/S1474-4422(18)30322-3.

    Article  Google Scholar 

  3. Sacco S, Braschinsky M, Ducros A, et al. European headache federation consensus on the definition of resistant and refractory migraine. J Headache Pain. 2020;21(1):76. https://doi.org/10.1186/s10194-020-01130-5.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Sevivas H, Fresco P. Treatment of resistant chronic migraine with anti-CGRP monoclonal antibodies: a systematic review. Eur J Med Res. 2022;27(1):86. https://doi.org/10.1186/s40001-022-00716-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Sacco S, Amin FM, Ashina M, et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update. J Headache Pain. 2022;23(1):67. https://doi.org/10.1186/s10194-022-01431-x.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Silberstein SD, Dodick DW, Bigal ME, et al. Fremanezumab for the preventive treatment of chronic migraine. N Engl J Med. 2017;377(22):2113–22. https://doi.org/10.1056/NEJMoa1709038.

    Article  CAS  PubMed  Google Scholar 

  7. Detke HC, Goadsby PJ, Wang S, et al. Galcanezumab in chronic migraine. Neurology. 2018;91(24):e2211–21. https://doi.org/10.1212/WNL.0000000000006640.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Riesenberg R, Gaul C, Stroud CE, et al. Long-term open-label safety study of galcanezumab in patients with episodic or chronic cluster headache. Cephalalgia. 2022;42(12):1225–35. https://doi.org/10.1177/03331024221103509.

    Article  PubMed  Google Scholar 

  9. Charles A, Pozo-Rosich P. Targeting calcitonin gene-related peptide: a new era in migraine therapy. Lancet. 2019;394(10210):1765–74. https://doi.org/10.1016/S0140-6736(19)32504-8.

    Article  CAS  PubMed  Google Scholar 

  10. Mavridis T, Deligianni C, Karagiorgis G, et al. Monoclonal antibodies targeting CGRP: from clinical studies to real-world evidence—What do we know so far? Pharmaceuticals (Basel). 2021;14(7):700. https://doi.org/10.3390/ph14070700.

    Article  CAS  PubMed  Google Scholar 

  11. Ihara K, Ohtani S, Watanabe N, et al. Predicting response to CGRP-monoclonal antibodies in patients with migraine in Japan: a single-centre retrospective observational study. J Headache Pain. 2023;24(1):23. https://doi.org/10.1186/s10194-023-01556-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Quintana S, Russo M, Manzoni GC, et al. Comparison study between erenumab, fremanezumab, and galcanezumab in the preventive treatment of high frequency episodic migraine and chronic migraine. Neurol Sci. 2022;43(9):5757–8. https://doi.org/10.1007/s10072-022-06254-x.

    Article  PubMed  Google Scholar 

  13. Torres-Ferrús M, Gallardo VJ, Alpuente A, et al. The impact of anti-CGRP monoclonal antibodies in resistant migraine patients: a real-world evidence observational study. J Neurol. 2021;268(10):3789–98. https://doi.org/10.1007/s00415-021-10523-8.

    Article  CAS  PubMed  Google Scholar 

  14. Iannone LF, Fattori D, Benemei S, et al. Long-term effectiveness of three anti-CGRP monoclonal antibodies in resistant chronic migraine patients based on the MIDAS score. CNS Drugs. 2022;36(2):191–202. https://doi.org/10.1007/s40263-021-00893-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Alex A, Vaughn C, Rayhill M. Safety and tolerability of 3 CGRP monoclonal antibodies in practice: a retrospective cohort study. Headache. 2020;60(10):2454–62. https://doi.org/10.1111/head.13956.

    Article  PubMed  Google Scholar 

  16. Caronna E, Gallardo VJ, Alpuente A, et al. Anti-CGRP monoclonal antibodies in chronic migraine with medication overuse: real-life effectiveness and predictors of response at 6 months. J Headache Pain. 2021;22(1):120. https://doi.org/10.1186/s10194-021-01328-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Alpuente A, Torre-Sune A, Caronna E, et al. Impact of anti-CGRP monoclonal antibodies on migraine attack accompanying symptoms: a real-world evidence study. Cephalalgia. 2023. https://doi.org/10.1177/03331024231177636.

    Article  PubMed  Google Scholar 

  18. Silvestro M, Tessitore A, di Clemente S, et al. Refractory migraine profile in CGRP-monoclonal antibodies scenario. Acta Neurol Scand. 2021;144(33):325–33. https://doi.org/10.1111/ane.13472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ornello R, Casalena A, Frattale I, et al. Real-life data on the efficacy and safety of erenumab in the Abruzzo region, central Italy. J Headache Pain. 2020;21(1):32. https://doi.org/10.1186/s10194-020-01102-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Karsan N, Gosalia H, Goadsby PJ. Molecular mechanisms of migraine: nitric oxide synthase and neuropeptides. Int J Mol Sci. 2023;24(15):11993. https://doi.org/10.3390/ijms241511993.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Labastida-Ramírez A, Caronna E, Gollion C, et al. Mode and site of action of therapies targeting CGRP signaling. J Headache Pain. 2023. https://doi.org/10.1186/s10194-023-01644-8.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kristoffersen ES, Lundqvist C. Medication-overuse headache: epidemiology, diagnosis and treatment. Ther Adv Drug Saf. 2014;5(2):87–99. https://doi.org/10.1177/2042098614522683.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Krymchantowski AV, Jevoux C, Krymchantowski AG, et al. Monoclonal antibodies for chronic migraine and medication overuse headache: a real-world study. Front Neurol. 2023;14:1129439. https://doi.org/10.3389/fneur.2023.1129439.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lampl C, MaassenVanDenBrink A, Deligianni CI, et al. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. J Headache Pain. 2023;24(1):56. https://doi.org/10.1186/s10194-023-01594-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Clinical Pharmacy and Therapeutics Research Group, Servicio de Farmacia Hospitalaria, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Biomedical Research Institute of Murcia (IMIB), Ctra. Madrid-Cartagena, s/n, 30120, El Palmar, Murcia, Spain

    E. Pons-Fuster, A. Mancebo-González, I. De Gorostiza-Frías & C. M. González-Ponce

  2. Headache Unit, Virgen de la Arrixaca University Clinical Hospital (HCUVA), Murcia, Spain

    O. Lozano-Caballero, S. Martín-Balbuena & C. Lucas-Ródenas

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  1. E. Pons-Fuster
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  2. O. Lozano-Caballero
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  3. S. Martín-Balbuena
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  4. C. Lucas-Ródenas
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  5. A. Mancebo-González
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  6. I. De Gorostiza-Frías
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Correspondence to E. Pons-Fuster.

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Pons-Fuster, E., Lozano-Caballero, O., Martín-Balbuena, S. et al. Anti‑CGRP monoclonal antibodies in resistant migraine: preliminary real-world effectiveness and clinical predictors of response at two years. Int J Clin Pharm (2024). https://doi.org/10.1007/s11096-024-01758-2

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