Monoclonal antibody erenumab for migraine prevention: a review of new data

Monoclonal antibodies (mAT) to calcitonin-gene-related peptide (CGRP) have become the fi rst class of preventive medications specifically designed to treat migraines. The article examines the mechanism of action of mAT from the standpoint of a modern view of the pathophysiology of migraine, discusses the issues of immunogenicity and drug interaction. The review describes in detail the monoclonal antibody erenumab, which became available in Russia from February 2020. The action of erenumab is associated with blocking the CGRP receptor, since it is the only one of the existing mAT that competes with the CGRP molecule for binding to the receptor. This review summarizes the pharmacological characteristics of erenumab, presents in detail the results of clinical trials with an emphasis on the publications of the last year. The article also presents the role of this method of treatment in real clinical practice: the eff ectiveness and safety of erenumab in various forms of migraine are described in detail, the possibility of transition (“reverse transformation”) from chronic migraine to episodic form on erenumab therapy is shown, impressive results of treatment of intractable cases in resistant and refractory migraines are presented. Erenumab is the only one of the mAT drugs for which the results of five-year clinical observations have been published, which have proved the sustained effectiveness and safety in long-term use, as well as the economic feasibility of using this therapeutic approach.

1. Charles A., Pozo-Rosich P. Targeting calcitonin generelated peptide: a new era in migraine therapy. Lancet. 2019;394(10210):1765–1774. https://doi.org/10.1016/S0140-6736(19)32504-8

2. Sirbu C.A., Ghinescu M.C., Axelerad A.D., Sirbu A.M., Ionita-Radu F. A new era for monoclonal antibodies with applications in neurology (Review). Exp. Ther. Med. 2021;21(1):86. https://doi.org/10.3892/etm.2020.9519

3. Wolff -Holz E., Tiitso K., Vleminckx C., Weise M. Evolution of the EU biosimilar framework: Past and future. BioDrugs. 2019;33:621–634.

4. Leung D., Wurst J.M., Liu T., Martinez R.M., Datta-Mannan A., Feng Y. Antibodies (Basel). Antibody Conjugates-Recent Advances and Future Innovations. 2020;9(1):2. https://doi.org/10.3390/antib9010002

5. Disease G.B.D., Injury I., Prevalence C. Global, regional, and national incidence, prevalence, andyears lived with disability for 328 diseases andinjuries for 195 countries, 1990–2016: a systematicanalysis for the global burden of Disease study. 2016. Lancet. 2017;390(10100):1211–59.

6. Filatova E.G., Osipova V.V., Tabeeva G.R., Parfenov V.A., Ekusheva E.V., Azimova Yu.E. et al. Diagnosis and treatment of migraine: Russian experts’ recommendations. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(4):4–14 (In Russian). https://doi.org/10.14412/2074-2711-2020-4-4-14

7. Charles A. The pathophysiology of migraine: implications for clinical management. Lancet Neurol. 2018;17(2):174–182. https://doi.org/10.1016/S1474-4422(17)30435-0

8. Ashina M., Goadsby P.J., Reuter U., Silberstein S., Dodick D.W., Xue F. et al. Long-term efficacy and safety of erenumab in migraine prevention: results from a 5-year, open-label treatment phase of a randomized clinical trial. Eur. J. Neurol. 2021 Jan 5. https://doi.org/10.1111/ene.14715.

9. Edvinsson L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache. 2017;57(Suppl 2):47–55.

10. Goadsby P.J., Reuter U., Hallstrom Y., Broessner G., Bonner J.H., Zhang F. et al. A controlled trial of erenumab for episodic migraine. N. Engl. J. Med. 2017;377(22):2123–2132. https://doi.org/10.1056/NEJMoa1705848

11. Dodick D.W., Ashina M., Brandes J.L., Kudrow D., Lanteri- Minet M., Osipova V. et al. ARISE: a phase3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026–37.

12. Tepper S., Ashina M., Reuter U., Brandes J.L., Dolezil D., Silberstein S. et al. Safety and efficacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425–434.

13. Goadsby P.J., Reuter U., Hallstrom Y., Broessner G., Bonner J.H., Zhang F. et al. One-year sustained efficacy of erenumab in episodic migraine. Results of the STRIVE study. Neurology. 2020;95:e469-e479. https://doi.org/10.1212/WNL.0000000000010019

14. Ashina M., Goadsby P.J, Reuter U., Silberstein S., Dodick D., Rippon G.A. et al. Long-term safety and tolerability of erenumab: Three-plus year results from a five-year open-label extension study in episodic migraine. Cephalalgia. 2019;39(11):1455–1464. DOI: 10.1177/0333102419854082.

15. Ziegeler C., Mehnert J., Asmussen K., May A. Central effects of erenumab in migraine patients: An event-related functional imaging study. Neurology. 2020;95(20):e2794–e2802. https://doi.org/10.1212/WNL.0000000000010740

16. Jain S., Silberstein S.D. Invited Commentary on Preventive Anti-MigraineTherapy (PAMT). Curr. Treat. Options Neurol. 2019;21:14. https://doi.org/10.1007/s11940-019-0555-4

17. Cohen J.M., Ning X., Kessle Y., Rasamoelisolo M., Campos V.R., Seminerio M.J. et al. Immunogenicity of biologic therapies for migraine: a review of current evidence. J. Headache Pain. 2021;22(1):3. https://doi.org/10.1186/s10194-020-01211-5

18. Vargas B., Starling A., Silberstein S. Erenumab Immunogenicity: a Pooled Analysis of Phase 2 and Phase 3 Migraine Prevention Clinical Trials (P4.098). Neurology. 2018;90 (15 Supplement) P4.098.

19. Szkutnik-Fiedler D. Pharmacokinetics, pharmacodynamics and drug–drug interactions of new anti-migraine drugs — lasmiditan, gepants, and calcitonin-gene-related peptide (CGRP) receptor monoclonal antibodies. Pharmaceutics. 2020;12:1180. https://doi.org/10.3390/pharmaceutics12121180; www.mdpi.com/journal/pharmaceutics

20. Sacco S., Bendtsen L., Ashina M., Reuter U., Terwindt G., Mitsikostas D.D. et al. European headache federation guideline on the use of monoclonal antibodies acting on the calcitonin gene related peptide or its receptor for migraine prevention. J. Headache Pain. 2019;20(1):6. https://doi.org/10.1186/s10194-018-0955-y

21. Tepper S.J., Ashina M., Reuter U., Brandes J.L., Doleži D., Silberstein S.D. et al. Long-term safety and effi cacy of erenumab in patients with chronic migraine: Results from a 52-week, openlabel extension study. Cephalalgia. 2020;40(6):543–553. https://doi.org/10.1177/0333102420912726

22. Lipton R.B., Tepper S.J., Silberstein S.D., Kudrow D., Ashina M., Reuter U. et al. Reversion from chronic migraine to episodic migraine following treatment with erenumab: Results of a post-hoc analysis of a randomized, 12-week, double-blind study and a 52-week, open-label extension. Cephalalgia. 2021;41(1):6–16. DOI: 10.1177/0333102420973994

23. Raff aelli B., Mussetto V., Israel H., Neeb L., Reuter U. Erenumab and galcanezumab in chronic migraine prevention: effects after treatment termination. J. Headache Pain. 2019;20(1):66. https://doi.org/10.1186/s10194-019-1018-8

24. De Matteis E., Aff aitati G., Frattale I., Caponnetto V., Pistoia F., Giamberardino M.A. et al. Early outcomes of migraine after erenumab discontinuation: data from a real-life setting. Neurol. Sci. 2021 Jan 2. https://doi.org/10.1007/s10072-020-05022-z

25. Sacco S., Braschinsky M., Ducros A., Lampl C., Little P., Maassen van den Brink A. et al. European headache federation consensus on the definition of resistant and refractory migraine: Developed with the endorsement of the European Migraine & Headache Alliance (EMHA). J. Headache Pain. 2020;21(1):76. https://doi.org/10.1186/s10194-020-01130-5

26. Lambru G., Hill B., Murphy M., Tylova I., Andreou A.P. A prospective real-world analysis of erenumab in refractory chronic migraine. J. Headache Pain. 2020;21:61. https://doi.org/10.1186/s10194-020-01127-0

27. Talbot J., Stuckey R., Crawford L., Weatherby S., Mullin S. Improvements in pain, medication use and quality of life in onabotulinumtoxinA- resistant chronic migraine patients following erenumab treatment — real world outcomes. J. Headache Pain. 2021;22(1):5. https://doi.org/10.1186/s10194-020-01214-2

28. 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 realworld experience. J. Headache Pain. 2020;21(1):69. https://doi.org/10.1186/s10194-020-01143-0

29. Mahon R., Lang A., Vo P., Huels J., Cooney P., Danyliv A. et al. Cost-effectiveness of erenumab for the preventive treatment of migraine in patients with prior treatment failures in Sweden. Pharmacoeconomics. 2021;39(3):357–372. https://doi.org/10.1007/s40273-020-00996-2

30. Tepper S.J., Diener H.C., Ashina M., Brandes J.L., Friedman D.I., Reuter U. et al. Erenumab in chronic migraine with medication overuse: Subgroup analysis of a randomized trial. Neurology. 2019;92(20):e2309-e2320. https://doi.org/10.1212/WNL.0000000000007497