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Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Efficacy and Safety

Drugs volume 79, pages 417–431 (2019)Cite this article

Abstract

Background

Novel therapeutic options with improved efficacy and safety profiles are needed for the prophylaxis of migraine. In recent years, the inhibition of calcitonin gene-related peptide (CGRP) signaling has attracted growing interest in the pharmacological research on migraine. Erenumab is the first fully human monoclonal antibody directed against the CGRP receptor to be approved for use in migraineurs.

Objective

To evaluate the efficacy and safety of erenumab as preventive treatment in patients with migraine using meta-analytical techniques.

Methods

Randomized, placebo-controlled, single- or double-blinded trials were identified through a systematic literature search (October week 4, 2018). Main outcomes included the changes from baseline in monthly migraine days (MMD) and monthly acute migraine-specific medication days (MSMD) at week 12, and the incidence of adverse events (AEs), severe AEs (SAEs) and treatment withdrawal due to AEs. Mean difference (MD) and risk ratio (RR) with 95% confidence intervals (95% CIs) were estimated.

Results

Across the five included trials, erenumab given as a subcutaneous injection at a monthly dosage of 70 mg and 140 mg was associated with a significantly greater reduction in baseline MMD (70 mg: MD − 1.3, 95% CI − 1.7 to − 1.0, p < 0.001; 140 mg: MD − 1.9, 95% CI − 2.3 to − 1.4, p < 0.001) and MSMD (70 mg: MD − 1.0, 95% CI − 1.6 to − 0.4, p < 0.001; 140 mg: MD − 1.8, 95% CI − 2.5 to − 1.1, p < 0.001) than placebo. There were no differences in the occurrence of AEs, SAEs, and drug withdrawal due to AEs between the erenumab and placebo groups.

Conclusions

Erenumab is an efficacious and well tolerated preventive treatment in adult patients with episodic and chronic migraine.

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References

  1. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380:2163–96.

    Article  Google Scholar 

  2. Headache Classification Subcommittee of the International Headache Society. The International Classification of Headache Disorders: 2nd edition. Cephalalgia. 2004;24 (Suppl. 1):9–160.

  3. Headache Classification Committee of the International Headache Society. The international classification of headache disorders, 3rd edition (beta version). Cephalalgia. 2013;33:629–808.

  4. Buse DC, Rupnow MF, Lipton RB. Assessing and managing all aspects of migraine: migraine attacks, migraine-related functional impairment, common comorbidities, and quality of life. Mayo Clin Proc. 2009;84:422–35.

    Article  Google Scholar 

  5. Serrano D, Manack AN, Reed ML, Buse DC, Varon SF, Lipton RB. Cost and predictors of lost productive time in chronic migraine and episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study. Value Health. 2013;16:31–8.

    Article  Google Scholar 

  6. Stokes M, Becker WJ, Lipton RB, Sullivan SD, Wilcox TK, Wells L, Manack A, Proskorovsky I, Gladstone J, Buse DC, Varon SF, Goadsby PJ, Blumenfeld AM. Cost of health care among patients with chronic and episodic migraine in Canada and the USA: results from the International Burden of Migraine Study (IBMS). Headache. 2011;51:1058–77.

    Article  Google Scholar 

  7. Bloudek LM, Stokes M, Buse DC, Wilcox TK, Lipton RB, Goadsby PJ, Varon SF, Blumenfeld AM, Katsarava Z, Pascual J, Lanteri-Minet M, Cortelli P, Martelletti P. Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS). J Headache Pain. 2012;13(5):361–78.

    CAS  Article  Google Scholar 

  8. Silberstein SD. Preventive Migraine treatment. Continuum (Minneap Minn). 2015;21:973–89.

    PubMed  PubMed Central  Google Scholar 

  9. Hepp Z, Dodick DW, Varon SF, Gillard P, Hansen RN, Devine EB. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35:478–88.

    Article  Google Scholar 

  10. Hepp Z, Dodick DW, Varon SF, Chia J, Matthew N, Gillard P, Hansen RN, Devine EB. Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: a retrospective claims analysis. Cephalalgia. 2017;37:470–85.

    Article  Google Scholar 

  11. Ho TW, Edvinsson L. Goadsby PJ CGRP and its receptors provide new insights into migraine pathophysiology. Nat Rev Neurol. 2010;6:573–82.

    CAS  Article  Google Scholar 

  12. Moore EL, Salvatore CA. Targeting a family B GPCR/RAMP receptor complex: CGRP receptor antagonists and migraine. Br J Pharmacol. 2012;166:66–78.

    CAS  Article  Google Scholar 

  13. Aimovig-FDA. Highlights of prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761077s000lbl.pdf. Accessed Oct 2018.

  14. European Medicines Agency. Summary of product characteristics. Aimovig. International non-proprietary name erenumab. https://www.ema.europa.eu/documents/product-information/aimovig-epar-product-information_en.pdf. Accessed October 2018.

  15. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

  16. Kawata AK, Hsieh R, Bender R, Shaffer S, Revicki DA, Bayliss M, Buse DC, Desai P, Sapra S, Ortmeier B, Hareendran A. Psychometric evaluation of a novel instrument assessing the impact of migraine on physical functioning: the migraine physical function impact diary. Headache. 2017;57:1385–98.

    Article  Google Scholar 

  17. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. Higgins JPT and Green S, editors. The Cochrane Collaboration, 2011. http://handbook-5-1.cochrane.org/. Accessed October 2018.

  18. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–58.

    Article  Google Scholar 

  19. Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, Silvestrini M. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs. 2018;78:1791–804.

    CAS  Article  Google Scholar 

  20. Lattanzi S, Brigo F, Grillo E, Cagnetti C, Verrotti A, Zaccara G, Silvestrini M. Adjunctive eslicarbazepine acetate in pediatric patients with focal epilepsy: a systematic review and meta-analysis. CNS Drugs. 2018;32:189–96.

    CAS  Article  Google Scholar 

  21. Lattanzi S, Brigo F, Cagnetti C, Trinka E, Silvestrini M. Efficacy and safety of adjunctive cannabidiol in patients with Lennox-Gastaut syndrome: a systematic review and meta-analysis. CNS Drugs. 2018;32:905–16.

    CAS  Article  Google Scholar 

  22. Lattanzi S, Grillo E, Brigo F, Silvestrini M. Efficacy and safety of perampanel in Parkinson’s disease. A systematic review with meta-analysis. J Neurol. 2018;265:733–740.

  23. Lattanzi S, Brigo F, Di Napoli M, Cagnetti C, Corradetti T, Silvestrini M. Endovascular treatment of symptomatic vertebral artery stenosis: a systematic review and meta-analysis. J Neurol Sci. 2018;391:48–53.

    Article  Google Scholar 

  24. Lattanzi S, Cagnetti C, Danni M, Provinciali L, Silvestrini M. Oral and intravenous steroids for multiple sclerosis relapse: a systematic review and meta-analysis. J Neurol. 2017;264:1697–704.

    CAS  Article  Google Scholar 

  25. Lattanzi S, Brigo F, Cagnetti C, Di Napoli M, Silvestrini M. Patent foramen ovale and cryptogenic stroke or transient ischemic attack: to close or not to close? A systematic review and meta-analysis. Cerebrovasc Dis. 2018;45:193–203.

    Article  Google Scholar 

  26. Sun H, Dodick DW, Silberstein S, Goadsby PJ, Reuter U, Ashina M, Saper J, Cady R, Chon Y, Dietrich J, Lenz R. Safety and efficacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15:382–90.

    CAS  Article  Google Scholar 

  27. Tepper S, Ashina M, Reuter U, Brandes JL, Doležil D, Silberstein S, Winner P, Leonardi D, Mikol D, Lenz R. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16:425–34.

    CAS  Article  Google Scholar 

  28. Goadsby PJ, Reuter U, Hallström Y, Broessner G, Bonner JH, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. A controlled trial of erenumab for episodic migraine. N Engl J Med. 2017;377:2123–32.

    CAS  Article  Google Scholar 

  29. Dodick DW, Ashina M, Brandes JL, Kudrow D, Lanteri-Minet M, Osipova V, Palmer K, Picard H, Mikol DD, Lenz RA. ARISE: a Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38:1026–37.

    Article  Google Scholar 

  30. Reuter U, Goadsby PJ, Lanteri-Minet M, Wen S4, Hours-Zesiger P, Ferrari MD, Klatt J. Efficacy and tolerability of erenumab in patients with episodic migraine in whom two-to-four previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392:2280–2287.

  31. European Medicines Agency. Assessment report. Aimovig. International non-proprietary name: erenumab. https://www.ema.europa.eu/documents/assessment-report/aimovig-epar-public-assessment-report_en.pdf. Accessed Dec 2018.

  32. Schwedt T, Reuter U, Tepper S, Ashina M, Kudrow D, Broessner G, Boudreau GP, McAllister P, Vu T, Zhang F, Cheng S, Picard H, Wen S, Kahn J, Klatt J, Mikol D. Early onset of efficacy with erenumab in patients with episodic and chronic migraine. J Headache Pain. 2018;19:92.

    Article  Google Scholar 

  33. Buse DC, Lipton RB, Hallström Y, Reuter U, Tepper SJ, Zhang F, Sapra S, Picard H, Mikol DD, Lenz RA. Migraine-related disability, impact, and health-related quality of life among patients with episodic migraine receiving preventive treatment with erenumab. Cephalalgia. 2018;38:1622–31.

    Article  Google Scholar 

  34. Silberstein SD, Neto W, Schmitt J, Jacobs D; MIGR-001 Study Group. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004;61:490–5.

  35. Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe S, Jacobs D; MIGR-002 Study Group. Topiramate for migraine prevention: a randomized controlled trial. JAMA. 2004;291:965–73.

  36. Vécsei L, Majláth Z, Szok D, Csáti A, Tajti J. Drug safety and tolerability in prophylactic migraine treatment. Expert Opin Drug Saf. 2015;14:667–81.

    Article  Google Scholar 

  37. Hepp Z, Bloudek LM, Varon SF. Systematic review of migraine prophylaxis adherence and persistence. J Manag Care Pharm. 2014;20:22–33.

    Article  Google Scholar 

  38. Russell FA, King R, Smillie SJ, Kodji X, Brain SD. Calcitonin gene-related peptide: physiology and pathophysiology. Physiol Rev. 2014;94:1099–142.

    CAS  Article  Google Scholar 

  39. Depre C, Antalik L, Starling A, Koren M, Eisele O, Lenz RA, Mikol DD. A randomized, double-blind, placebo-controlled study to evaluate the effect of erenumab on exercise time during a treadmill test in patients with stable angina. Headache. 2018;58:715–23.

    Article  Google Scholar 

  40. Petersen KA, Birk S, Lassen LH, Kruuse C, Jonassen O, Lesko L, Olesen J. The CGRP-antagonist, BIBN4096BS does not affect cerebral or systemic haemodynamics in healthy volunteers. Cephalalgia. 2005;25:139–47.

    CAS  Article  Google Scholar 

  41. Van der Schueren BJ, Blanchard R, Murphy MG, Palcza J, De Lepeleire I, Van Hecken A, Depré M, de Hoon JN. The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men. Br J Clin Pharmacol. 2011;71:708–17.

    Article  Google Scholar 

  42. Jain S, Yuan H, Spare N, Silberstein SD. Erenumab in the treatment of migraine. Pain Manag. 2018;8:415–26.

    Article  Google Scholar 

  43. Zhu Y, Liu Y, Zhao J, Han Q, Liu L, Shen X. The efficacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis. Neurol Sci. 2018;39:2097–106.

    Article  Google Scholar 

  44. Majima M, Ito Y, Hosono K, Amano H. CGRP/CGRP receptor antibodies: potential adverse effects due to blockade of neovascularization? Trends Pharmacol Sci. 2018. https://doi.org/10.1016/j.tips.2018.11.003.

  45. Edvinsson L. CGRP antibodies as prophylaxis in migraine. Cell. 2018;175:1719.

    CAS  Article  Google Scholar 

  46. Walker CS, Eftekhari S, Bower RL, Wilderman A, Insel PA, Edvinsson L, Waldvogel HJ, Jamaluddin MA, Russo AF, Hay DL. A second trigeminal CGRP receptor: function and expression of the AMY1 receptor. Ann Clin Transl Neurol. 2015;2:595–608.

    CAS  Article  Google Scholar 

  47. Walker CS, Hay DL. CGRP in the trigeminovascular system: a role for CGRP, adrenomedullin and amylin receptors? Br J Pharmacol. 2013;170:1293–307.

    CAS  Article  Google Scholar 

  48. Sun H, Gavva N, Xu C. Inhibitors of CGRP function differentially affect calcitonin-family ligand/receptor interactions. Headache 2015;55(suppl S5):252.

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Author information

Affiliations

  1. Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Via Conca 71, 60020, Ancona, Italy

    Simona Lattanzi, Tommaso Corradetti & Mauro Silvestrini

  2. Department of Neuroscience, Biomedicine and Movement Science, University of Verona, Verona, Italy

    Francesco Brigo

  3. Division of Neurology, “Franz Tappeiner” Hospital, Merano, BZ, Italy

    Francesco Brigo

  4. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria

    Eugen Trinka

  5. Center for Cognitive Neuroscience, Salzburg, Austria

    Eugen Trinka

  6. Public Health, Health Services Research and HTA, University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria

    Eugen Trinka

  7. Neurology Unit, Campus Bio-Medico University, Rome, Italy

    Fabrizio Vernieri

  8. Clinic of Neurosurgery, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy

    Mauro Dobran

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  1. Simona Lattanzi
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  2. Francesco Brigo
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Corresponding author

Correspondence to Simona Lattanzi.

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Funding

No funding was received for the conduct of this study.

Conflict of interest

Simona Lattanzi, Fabrizio Vernieri, Tommaso Corradetti, Mauro Dobran, and Mauro Silvestrini have no conflicts of interest directly relevant to the content of this study. Francesco Brigo has acted as a consultant for Eisai. Eugen Trinka has received speaker’s honoraria from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, Sunovion Pharmaceuticals Inc., LivaNova and Novartis; consultancy funds from UCB, Biogen, Gerot-Lannach, Bial, Eisai, Takeda, Newbridge, GW Pharmaceuticals, Sunovion Pharmaceuticals Inc., and Novartis; directorship funds from Neuroconsult GmbH. E. Trinka’s Institution received grants from Biogen, Red Bull, Merck, UCB, European Union, FWF Österreichischer Fond zur Wissenschaftsförderung, and Bundesministerium für Wissenschaft und Forschung.

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Lattanzi, S., Brigo, F., Trinka, E. et al. Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Efficacy and Safety. Drugs 79, 417–431 (2019). https://doi.org/10.1007/s40265-019-01069-1

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