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Effectiveness of Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Prevention of Migraine: A Systematic Review and Meta-Analysis of Observational Cohort Studies

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Abstract

Background and Objective

Migraine is a neurological disorder characterized by episodes of moderate-to-severe headache. The emergence of drugs derived from monoclonal antibodies specific for the calcitonin gene has brought forth a therapeutic option for patients in whom the traditional treatments have failed. This study aimed to evaluate the clinical effectiveness of calcitonin gene-related peptide antibodies in the prevention of migraine through a systematic review and meta-analysis of observational cohort studies.

Methods

A literature search for evidence was performed in electronic databases for observational studies that evaluated adult patients with migraine receiving calcitonin gene-related peptide receptor antagonists (e.g. erenumab, fremanezumab, galcanezumab and eptinezumab) and reported effectiveness outcomes (mean reduction in monthly migraine/headache days, and proportion of patients with 50% or greater reduction in migraine/headache days).

Results

During the screening process, 47 records were included for data extraction and qualitative and quantitative analyses. The overall rate of patients with a reduction of at least 50% of mean monthly migraine days was 54% (95% CI 49–59%), and overall mean monthly migraine reduction was about 7.7 days (95% CI 8.4–7.0 days). Regarding the outcome ≥ 50% reduction in mean monthly headache reduction, the overall rate of patients with a reduction of at least 50% was 57% (95% CI 48–64%), and the overall mean monthly headache reduction was approximately 8.8 days (95% CI 10.1–7.5 days). Subgroup analyses considering the drug treatment used and type of migraine were consistent with previous results.

Conclusions

The use of calcitonin gene-related peptide antibodies in real-world studies to prevent migraine demonstrates promising effectiveness outcomes, in agreement with those reported in previously published randomized clinical trial reports.

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 References

  1. Ha DK, Kim MJ, Han N, Kwak JH, Baek IH. Comparative efficacy of oral calcitonin-gene-related peptide antagonists for the treatment of acute migraine: updated meta-analysis. Clin Drug Investig. 2021;41:119–32.

    Article  CAS  PubMed  Google Scholar 

  2. Buse DC, Greisman JD, Baigi K, Lipton RB. Migraine progression: a systematic review. Headache. 2019;59:306–38.

    Article  PubMed  Google Scholar 

  3. Ashina M, Katsarava Z, Do TP, Buse DC, Pozo-Rosich P, Özge A, et al. Migraine: epidemiology and systems of care. Lancet. 2021;397:1485–95.

    Article  PubMed  Google Scholar 

  4. Lipton RB. Chronic migraine, classification, differential diagnosis, and epidemiology. Headache J Head Face Pain. 2011;51:77–83.

    Article  Google Scholar 

  5. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68:343–9.

    Article  CAS  PubMed  Google Scholar 

  6. Weatherall MW. The diagnosis and treatment of chronic migraine. Ther Adv Chronic Dis. 2015;6:115–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ha H, Gonzalez A. Migraine headache prophylaxis. Am Fam Physician. 2019;99:17–24.

    PubMed  Google Scholar 

  8. Becker WJ. Acute migraine treatment in adults. Headache. 2015;55:778–93.

    Article  PubMed  Google Scholar 

  9. Robbins MS. Diagnosis and management of headache: a review. JAMA. 2021;325:1874–85.

    Article  PubMed  Google Scholar 

  10. Sacco S, Amin FM, Ashina M, Bendtsen L, Deligianni CI, Gil-Gouveia R, et al. European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention—2022 update. Expert Opin Pharmacother. 2022;2022(23):67.

    Google Scholar 

  11. George N, Tepper SJ. Novel migraine treatments: a review. J Oral Facial Pain Headache. 2023;37:25–32.

    Article  PubMed  Google Scholar 

  12. Haghdoost F, Puledda F, Garcia-Azorin D, Huessler E-M, Messina R, Pozo-Rosich P. Evaluating the efficacy of CGRP mAbs and gepants for the preventive treatment of migraine: a systematic review and network meta-analysis of phase 3 randomised controlled trials. Cephalalgia. 2023;43:3331024231159366.

    Article  PubMed  Google Scholar 

  13. Forbes RB, McCarron M. Efficacy and contextual (placebo) effects of CGRP antibodies for migraine: systematic review and meta-analysis. Headache. 2020;60:1542–57.

    Article  PubMed  Google Scholar 

  14. Soni P, Chawla E. Efficacy and safety of anti-calcitonin gene-related peptide monoclonal antibodies for treatment of chronic migraine: a systematic review and network meta-analysis. Clin Neurol Neurosurg. 2021;209:106893.

    Article  PubMed  Google Scholar 

  15. Lampl C, MaassenVanDenBrink A, Deligianni CI, Gil-Gouveia R, Jassal T, Sanchez-Del-Rio M, et al. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. J Headache Pain. 2023;24:56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vernieri F, Brunelli N, Marcosano M, Aurilia C, Egeo G, Lovati C, et al. Maintenance of response and predictive factors of 1-year GalcanezumAb treatment in real-life migraine patients in Italy: The multicenter prospective cohort GARLIT study. Eur J Neurol. 2023;30:224–34.

    Article  PubMed  Google Scholar 

  17. Barbanti P, Egeo G, Aurilia C, Altamura C, Onofrio F, Finocchi C, et al. Predictors of response to anti-CGRP monoclonal antibodies: a 24-week, multicenter, prospective study on 864 migraine patients. J Headache Pain. 2022;2022(23):138.

    Article  Google Scholar 

  18. Ferreira VL, Leonart LP, Tonin FS, Borba HHL, Pontarolo R. Sustained virological response in special populations with chronic hepatitis C using interferon-free treatments: a systematic review and meta-analysis of observational cohort studies. Clin Drug Investig. 2018;38:389–400.

    Article  CAS  PubMed  Google Scholar 

  19. Manchikanti L, Datta S, Smith HS, Hirsch JA. Evidence-based medicine, systematic reviews, and guidelines in interventional pain management: part 6. Systematic reviews and meta-analyses of observational studies. Pain Phys. 2009;12:819–50.

    Article  Google Scholar 

  20. Schünemann HJ, Tugwell P, Reeves BC, Akl EA, Santesso N, Spencer FA, et al. Non-randomized studies as a source of complementary, sequential or replacement evidence for randomized controlled trials in systematic reviews on the effects of interventions. Res Synth Methods. 2013;4:49–62.

    Article  PubMed  Google Scholar 

  21. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, The PRISMA, et al. statement: an updated guideline for reporting systematic reviews. BMJ. 2020;2021:372.

    Google Scholar 

  22. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions version 6.3 (updated February 2022). Cochrane. 2022.

  23. Turner RM, Bird SM, Higgins JP. The impact of study size on meta-analyses: examination of underpowered studies in Cochrane reviews. PLoS ONE. 2013;8:e59202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. 2023. www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 8 Aug 2023.

  25. Alsaadi T, Noori S, Varakian R, Youssef S, Almadani A. Real-world experience of erenumab in patients with chronic or episodic migraine in the UAE. BMC Neurol. 2022;22:221.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Alex A, Vaughn C, Rayhill M. Safety and tolerability of 3 CGRP monoclonal antibodies in practice: a retrospective cohort study. Headache. 2020;60:2454–62.

    Article  PubMed  Google Scholar 

  27. Alpuente A, Gallardo VJ, Caronna E, Torres-Ferrus M, Pozo-Rosich P. In search of a gold standard patient-reported outcome measure to use in the evaluation and treatment-decision making in migraine prevention. A real-world evidence study. J Headache Pain. 2021;22:151.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Andreou AP, Fuccaro M, Hill B, Murphy M, Caponnetto V, Kilner R, et al. Two-year effectiveness of erenumab in resistant chronic migraine: a prospective real-world analysis. J Headache Pain. 2022;2022(23):139.

    Article  Google Scholar 

  29. Baraldi C, Castro FL, Cainazzo MM, Pani L, Guerzoni S. Predictors of response to erenumab after 12 months of treatment. Brain Behav. 2021;11: e2260.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Barbanti P, Aurilia C. Long-term (48 weeks) effectiveness, safety, and tolerability of erenumab in the prevention of high-frequency episodic and chronic migraine in a real world: results of the EARLY 2 study. Headache. 2021;61:1351–63.

    Article  PubMed  Google Scholar 

  31. Becker WJ, Spacey S, Leroux E, Giammarco R, Gladstone J, Christie S, et al. A real-world, observational study of erenumab for migraine prevention in Canadian patients. Headache. 2022;62:522–9.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Belvís R, Irimia P, Pozo-Rosich P, González-Oria C, Cano A, Viguera J, et al. MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention. J Headache Pain. 2021;22:74.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Caso-González A, Leralta-González C, Sanz-Alonso V, Iturbe-Heras M, Hernando-de la Bárcena I, Obaldia-Alaña C. Clinical experience with erenumab during the first year of treatment. JAMA Neurol. 2022;74:8–14.

    Google Scholar 

  34. Cainazzo MM, Baraldi C. Erenumab for the preventive treatment of chronic migraine complicated with medication overuse headache: an observational, retrospective, 12-month real-life study. Neurol Sci. 2021;42:4193–202.

    Article  PubMed  Google Scholar 

  35. Lowe M, Murray L, Tyagi A, Gorrie G, Miller S, Dani K. Efficacy of erenumab and factors predicting response after 3 months in treatment resistant chronic migraine: a clinical service evaluation. J Headache Pain. 2022;23:86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Cheng S, Jenkins B, Limberg N, Hutton E. Erenumab in chronic migraine: an Australian experience. Expert Rev Neurother. 2020;60:2555–62.

    Google Scholar 

  37. Cullum CK, Do TP, Ashina M, Bendtsen L, Hugger SS, Iljazi A, et al. Real-world long-term efficacy and safety of erenumab in adults with chronic migraine: a 52-week, single-center, prospective, observational study. Eur J Med Res. 2022;23:61.

    CAS  Google Scholar 

  38. De Icco R, Vaghi G, Allena M, Ghiotto N, Guaschino E, Martinelli D, et al. Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial. J Headache Pain. 2022;23:123.

    Article  PubMed  PubMed Central  Google Scholar 

  39. De Matteis E, Affaitati G, Frattale I, Caponnetto V, Pistoia F, Giamberardino MA, et al. Early outcomes of migraine after erenumab discontinuation: data from a real-life setting. Expert Opin Drug Saf. 2021;42:3297–303.

    Google Scholar 

  40. de Vries LS, Verhagen IE, van den Hoek TC, MaassenVanDenBrink A, Terwindt GM. Treatment with the monoclonal calcitonin gene-related peptide receptor antibody erenumab: a real-life study. Eur J Neurol. 2021;28:4194–203.

    Article  Google Scholar 

  41. Dinh BBK, Aziz WH, Terruzzi A, Krieger DW. Initial experience with novel CGRP-receptor inhibitor therapy in migraine in the United Arab Emirates: a retrospective observational study. BMC Neurol. 2021;21:486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Driessen MT, Cohen JM, Patterson-Lomba O, Thompson SF, Seminerio M, Carr K, et al. Real-world effectiveness of fremanezumab in migraine patients initiating treatment in the United States: results from a retrospective chart study. J Headache Pain. 2022;23:47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Tziakouri A, Tsangari H, Michaelides C. Assessment of the effect of erenumab on efficacy and quality-of-life parameters in a cohort of migraine patients with treatment failure in Cyprus. Front Neurol. 2021;2021:12.

    Google Scholar 

  44. Khalil M, Moreno-Ajona D. Erenumab in chronic migraine: experience from a UK tertiary centre and comparison with other real-world evidence. Eur J Neurol. 2022;29:2473–80.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Kwon S. Real-world efficacy of galcanezumab for the treatment of migraine in Korean patients. Neurol Sci. 2022;42:705–14.

    Google Scholar 

  46. Lambru G, Hill B, Murphy M, Tylova I, Andreou AP. A prospective real-world analysis of erenumab in refractory chronic migraine. J Headache Pain. 2020;21:61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Altamura C, Brunelli N. Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational, longitudinal, cohort multicenter GARLIT experience. J Neurol. 2022;269:5848–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Mahović D, Bračić M, Jakuš L, Vukovic Cvetkovic V, Krpan M. Effectiveness and safety of erenumab in chronic migraine: a Croatian real-world experience. Clin Neurol Neurosurg. 2022;214: 107169.

    Article  PubMed  Google Scholar 

  49. Zecca C, Cargnin S, Schankin C, Giannantoni NM, Viana M, Maraffi I, et al. Clinic and genetic predictors in response to erenumab. Eur J Neurol. 2022;29:1209–17.

    Article  PubMed  PubMed Central  Google Scholar 

  50. McAllister P, Lamerato L, Krasenbaum LJ, Cohen JM, Tangirala K, Thompson S, et al. Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States. J Headache Pain. 2021;22:156.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Morales Bacas E, Portilla Cuenca JC, Romero Cantero V, García Gorostiaga I, Martínez Acevedo M, Casado-Naranjo I. Experience with erenumab: data from real clinical practice. Neurol Perspect. 2022;2:111–6.

    Article  Google Scholar 

  52. Ornello R, Casalena A, Frattale I, Gabriele A, Affaitati G, Giamberardino MA, et al. Real-life data on the efficacy and safety of erenumab in the Abruzzo region, central Italy. J Headache Pain. 2020;21:32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ornello R, Casalena A, Frattale I, Caponnetto V, Gabriele A, Affaitati G, et al. Conversion from chronic to episodic migraine in patients treated with erenumab: real-life data from an Italian region. J Headache Pain. 2020;21:102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Ornello R, Baraldi C, Guerzoni S, Lambru G, Fuccaro M, Raffaelli B, et al. Gender differences in 3-month outcomes of erenumab treatment—study on efficacy and safety of treatment with erenumab in men. Front Neurol. 2021;2021:12.

    Google Scholar 

  55. Ornello R, Baraldi C, Guerzoni S, Lambru G, Andreou AP, Raffaelli B, et al. Comparing the relative and absolute effect of erenumab: is a 50% response enough? Results from the ESTEEMen study. Pain Manag. 2022;23:38.

    CAS  Google Scholar 

  56. Pensato U, Baraldi C, Favoni V, Cainazzo MM, Torelli P, Querzani P, et al. Real-life assessment of erenumab in refractory chronic migraine with medication overuse headache. Brain Sci. 2022;43:1273–80.

    Google Scholar 

  57. Raffaelli B, Kalantzis R, Mecklenburg J, Overeem LH, Neeb L, Gendolla A, et al. Erenumab in Chronic migraine patients who previously failed five first-line oral prophylactics and onabotulinumtoxina: a dual-center retrospective observational study. Front Neurol. 2020;2020:11.

    Google Scholar 

  58. Raffaelli B, Terhart M, Mecklenburg J, Neeb L, Overeem LH, Siebert A, et al. Resumption of migraine preventive treatment with CGRP(-receptor) antibodies after a 3-month drug holiday: a real-world experience. J Headache Pain. 2022;23:40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Robblee J, Devick KL, Mendez N, Potter J, Slonaker J, Starling AJ. Real-world patient experience with erenumab for the preventive treatment of migraine. Headache. 2020;60:2014–25.

    Article  PubMed  Google Scholar 

  60. Russo A, Silvestro M, Scotto-di-Clemente F, Trojsi F, Bisecco A, Bonavita S, et al. Multidimensional assessment of the effects of erenumab in chronic migraine patients with previous unsuccessful preventive treatments: a comprehensive real-world experience. J Headache Pain. 2020;21:69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Salem-Abdou H, Simonyan D, Puymirat J. Identification of predictors of response to erenumab in a cohort of patients with migraine. Cephalalgia Rep. 2021;2021:4.

    Google Scholar 

  62. Scheffler A, Messel O, Wurthmann S, Nsaka M, Kleinschnitz C, Glas M, et al. Erenumab in highly therapy-refractory migraine patients: first German real-world evidence. J Headache Pain. 2020;21:84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Schiano-di-Cola F, Caratozzolo S, Venturelli E, Balducci U, Sidoti V, Pari E, et al. Erenumab discontinuation after 12-month treatment: a multicentric, observational real-life study. Neurol Clin Pr. 2021;11:834–9.

    Google Scholar 

  64. Schiano-di-Cola F, Rao R, Caratozzolo S, Di Cesare M, Venturelli E, Balducci U, et al. Erenumab efficacy in chronic migraine and medication overuse: a real-life multicentric Italian observational study. Neurol Sci. 2020;41:489–90.

    Article  PubMed  Google Scholar 

  65. Schoenen J, Timmermans G, Nonis R, Manise M, Fumal A, Gérard P. Erenumab for migraine prevention in a 1-year compassionate use program: efficacy, tolerability, and differences between clinical phenotypes. Front Neurol. 2021;2021:12.

    Google Scholar 

  66. Silvestro M, Tessitore A, Orologio I, De Micco R, Tartaglione L, Trojsi F, et al. Galcanezumab effect on “whole pain burden” and multidimensional outcomes in migraine patients with previous unsuccessful treatments: a real-world experience. Headache. 2022;23:69.

    CAS  Google Scholar 

  67. Straube A, Stude P, Gaul C, Schuh K, Koch M. Real-world evidence data on the monoclonal antibody erenumab in migraine prevention: perspectives of treating physicians in Germany. J Headache Pain. 2021;22:133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gantenbein AR, Agosti R, Kamm CP, Landmann G, Meier N, Merki-Feld GS, et al. Swiss QUality of life and healthcare impact Assessment in a Real-world Erenumab treated migraine population (SQUARE study): interim results. J Headache Pain. 2022;23:142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Viudez-Martínez A, Pascual-Carrasco A, Beltrán-Blasco I, Hernandez-Lorido R. Effectiveness and safety of erenumab and galcanezumab in the prevention of chronic and episodic migraine: A retrospective cohort study. Cephalalgia. 2022;47:814–23.

    Google Scholar 

  70. Storch P, Burow P, Möller B, Kraya T, Heintz S, Politz N, et al. Pooled retrospective analysis of 70 mg erenumab in episodic and chronic migraine: a two tertiary headache centers experience during clinical practice. Acta Neurol Belg. 2022;122:931–7.

    Article  CAS  PubMed  Google Scholar 

  71. Saylor D, Steiner TJ. The global burden of headache. Semin Neurol. 2018;38:182–90.

    Article  PubMed  Google Scholar 

  72. Burch RC, Buse DC, Lipton RB. Migraine: epidemiology, burden, and comorbidity. Neurol Clin. 2019;37:631–49.

    Article  PubMed  Google Scholar 

  73. Agosti R. Migraine burden of disease: from the patient’s experience to a socio-economic view. Headache. 2018;58(Suppl 1):17–32.

    Article  PubMed  Google Scholar 

  74. Rosignoli C, Ornello R, Onofri A, Caponnetto V, Grazzi L, Raggi A, et al. Applying a biopsychosocial model to migraine: rationale and clinical implications. J Headache Pain. 2022;23:100.

    Article  PubMed  PubMed Central  Google Scholar 

  75. Ailani J, Burch RC, Robbins MS, Society the B of D of the AH. The American Headache Society Consensus Statement: update on integrating new migraine treatments into clinical practice. Headache J Head Face Pain. 2021;61:1021–39.

    Article  Google Scholar 

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Correspondence to Roberto Pontarolo.

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Vinicius L. Ferreira: designed the study, collected and analysed the data, undertook the statistical analysis, wrote the first draft of the manuscript and approved the final version of the manuscript. Felipe F. Mainka: analysed the data, undertook the statistical analysis, wrote the first draft of the manuscript and approved the final version of the manuscript. Astrid Wiens: edited and reviewed the manuscript and approved the final version of the manuscript. Roberto Pontarolo: conceptualized and designed the study, supervised the project and approved the final version of the manuscript.

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Ferreira, V.L., Mainka, F.F., Wiens, A. et al. Effectiveness of Calcitonin Gene-Related Peptide Monoclonal Antibodies in the Prevention of Migraine: A Systematic Review and Meta-Analysis of Observational Cohort Studies. Clin Drug Investig 43, 669–680 (2023). https://doi.org/10.1007/s40261-023-01301-7

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