r-n-jРоссийский неврологический журналRussian neurological journal2658-79472686-7192МИА10.30629/2658-7947-2021-26-3-4-14r-n-j-182Research ArticleОБЗОРЫREVIEWSПятилетний опыт применения нового класса препаратов для таргетной профилактической терапии мигрениFive-year experience of using a new class of drugs for targeted preventive therapy of migrainehttps://orcid.org/0000-0001-6437-232XАмелинА. В.AmelinA. V.

Санкт-Петербург

Saint Petersburg

avamelin@mail.ruhttps://orcid.org/0000-0002-6141-486XСоколовА. Ю.SokolovA. Yu.

Санкт-Петербург

Saint Petersburg

alexey.y.sokolov@gmail.comhttps://orcid.org/0000-0003-4409-9615ВагановаЮ. С.VaganovaYu. S.

Санкт-Петербург

Saint Petersburg

ulianasamul@yandex.ruФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава РоссииРоссияPavlov First Saint Petersburg State Medical UniversityRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава России; ФГБУН «Институт физиологии им. И.П. Павлова» Российской академии наукРоссияPavlov First Saint Petersburg State Medical University; Pavlov Institute of Physiology, Russian Academy of SciencesRussian Federation202120072021263414Copyright © Амелин А.В., Соколов А.Ю., Ваганова Ю.С., 20212021Амелин А.В., Соколов А.Ю., Ваганова Ю.С.Amelin A.V., Sokolov A.Y., Vaganova Y.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.r-n-j.com/jour/article/view/182

Статья посвящена новому классу антимигренозных препаратов — моноклональным антителам (мАТ), нарушающим передачу сигнала кальцитонин-ген родственного пептида (КГРП). Кратко рассматриваются биологические эффекты КГРП в периферической и центральной нервной системе и его роль в патогенезе мигрени. Анализируются данные систематических обзоров рандомизированных клинических исследований эффективности и безопасности мАТ к КГРП (фреманезумаб, эптинезумаб и галканезумаб) и его рецептору (эренумаб) при эпизодической и хронической мигрени. Обсуждаются результаты пятилетнего применения эренумаба в рамках клинических исследований и реальной практики.

This article deals with new migraine therapy, monoclonal antibodies against calcitonin gene related peptide (CGRP) and its receptor. The review represents a brief discussion of CGRP biological eff ects in the peripheral and central nervous system, and the role of CGRP in the migraine pathogenesis. Data of systematic reviews of randomized clinical research about the effi cacy and safety of monoclonal antibodies against CGRP (fremanezumab, eptinezumab and galkanezumab) and its receptor (erenumab) in patients with episodic and chronic migraine are included and analyzed. The results of fi ve-year use of erenumab in clinical research and in real practice are discussed and compared.

мигренькальцитонин-ген родственный пептидпрофилактическое лечениемоноклональные антителаэренумабфреманезумабгалканезумабэптинезумабmigrainecalcitonin gene related peptidepreventive treatmentmonoclonal antibodieserenumabfremanezumabeptinezumabgalkanezumabReferencesRusso A.F. CGRP-based Migraine Therapeutics: How Might They Work, Why So Safe, and What Next? ACS Pharmacol Transl Sci. 2019;2(1):2–8. https://doi.org/10.1021/acsptsci.8b00036. Epub 2018 Nov 5. PMID: 31559394; PMCID: PMC6761833.Russo A.F. CGRP-based Migraine Therapeutics: How Might They Work, Why So Safe, and What Next? ACS Pharmacol Transl Sci. 2019;2(1):2–8. https://doi.org/10.1021/acsptsci.8b00036. Epub 2018 Nov 5. PMID: 31559394; PMCID: PMC6761833.Iyengar S., Johnson K.W., Ossipov M.H., Aurora S.K. CGRP and the Trigeminal System in Migraine. Headache. 2019;59(5):659–681. https://doi.org/10.1111/head.13529Iyengar S., Johnson K.W., Ossipov M.H., Aurora S.K. CGRP and the Trigeminal System in Migraine. Headache. 2019;59(5):659–681. https://doi.org/10.1111/head.13529Edvinsson L., Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia. 2019;39(3):366–373. https://doi.org/10.1177/0333102417736900Edvinsson L., Warfvinge K. Recognizing the role of CGRP and CGRP receptors in migraine and its treatment. Cephalalgia. 2019;39(3):366–373. https://doi.org/10.1177/0333102417736900Edvinsson L. The CGRP Pathway in Migraine as a Viable Target for Therapies. Headache. 2018;58 Suppl 1:33-47. https://doi.org/10.1111/head.13305. PMID: 29697153Edvinsson L. The CGRP Pathway in Migraine as a Viable Target for Therapies. Headache. 2018;58 Suppl 1:33-47. https://doi.org/10.1111/head.13305. PMID: 29697153Messlinger K. The big CGRP fl ood — sources, sinks and signalling sites in the trigeminovascular system. J. Headache Pain. 2018;19(1):22. Published 2018 Mar 12. https://doi.org/10.1186/s10194-018-0848-0Messlinger K. The big CGRP fl ood — sources, sinks and signalling sites in the trigeminovascular system. J. Headache Pain. 2018;19(1):22. Published 2018 Mar 12. https://doi.org/10.1186/s10194-018-0848-0Holland P.R., Saengjaroentham C., Vila-Pueyo M. The role of the brainstem in migraine: Potential brainstem eff ects of CGRP and CGRP receptor activation in animal models. Cephalalgia. 2019;39(3):390–402. https://doi.org/10.1177/0333102418756863Holland P.R., Saengjaroentham C., Vila-Pueyo M. The role of the brainstem in migraine: Potential brainstem eff ects of CGRP and CGRP receptor activation in animal models. Cephalalgia. 2019;39(3):390–402. https://doi.org/10.1177/0333102418756863De Matteis E., Guglielmetti M., Ornello R., Spuntarelli V., Martelletti P., Sacco S. Targeting CGRP for migraine treatment: mechanisms, antibodies, small molecules, perspectives. Expert Rev. Neurother. 2020;20(6):627–641. https://doi.org/10.1080/14737175.2020.1772758De Matteis E., Guglielmetti M., Ornello R., Spuntarelli V., Martelletti P., Sacco S. Targeting CGRP for migraine treatment: mechanisms, antibodies, small molecules, perspectives. Expert Rev. Neurother. 2020;20(6):627–641. https://doi.org/10.1080/14737175.2020.1772758Levy D., Labastida-Ramirez A., Maassen Van Den Brink A. Current understanding of meningeal and cerebral vascular function underlying migraine headache. Cephalalgia. 2019;39(13):1606–1622. https://doi.org/10.1177/0333102418771350. Epub 2018 Jun 21. PMID: 29929378.Levy D., Labastida-Ramirez A., Maassen Van Den Brink A. Current understanding of meningeal and cerebral vascular function underlying migraine headache. Cephalalgia. 2019;39(13):1606–1622. https://doi.org/10.1177/0333102418771350. Epub 2018 Jun 21. PMID: 29929378.Ashina M., Hansen J.M., Do T.P., Melo-Carrillo A., Burstein R., Moskowitz M.A. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18(8):795–804. https://doi.org/10.1016/S1474-4422 (19)30185-1. Epub 2019 May 31. PMID: 31160203; PMCID: PMC7164539Ashina M., Hansen J.M., Do T.P., Melo-Carrillo A., Burstein R., Moskowitz M.A. Migraine and the trigeminovascular system-40 years and counting. Lancet Neurol. 2019;18(8):795–804. https://doi.org/10.1016/S1474-4422 (19)30185-1. Epub 2019 May 31. PMID: 31160203; PMCID: PMC7164539Hoff mann J., Baca S.M., Akerman S. Neurovascular mechanisms of migraine and cluster headache. J. Cereb. Blood Flow Metab. 2019;39(4):573–594. https://doi.org/10.1177/0271678X17733655. Epub 2017 Sep 26. PMID: 28948863; PMCID: PMC6446418Hoff mann J., Baca S.M., Akerman S. Neurovascular mechanisms of migraine and cluster headache. J. Cereb. Blood Flow Metab. 2019;39(4):573–594. https://doi.org/10.1177/0271678X17733655. Epub 2017 Sep 26. PMID: 28948863; PMCID: PMC6446418Messlinger K., Russo A.F. Current understanding of trigeminal ganglion structure and function in headache. Cephalalgia. 2019;39(13):1661–1674. https://doi.org/10.1177/0333102418786261. Epub 2018 Jul 10. PMID: 29989427; PMCID: PMC7007999Messlinger K., Russo A.F. Current understanding of trigeminal ganglion structure and function in headache. Cephalalgia. 2019;39(13):1661–1674. https://doi.org/10.1177/0333102418786261. Epub 2018 Jul 10. PMID: 29989427; PMCID: PMC7007999Summ O., Charbit A.R., Andreou A.P., Goadsby P.J. Modulation of nocioceptive transmission with calcitonin gene-related peptide receptor antagonists in the thalamus. Brain. 2010;133(9):2540–8. https://doi.org/10.1093/brain/awq224. PMID: 20802202Summ O., Charbit A.R., Andreou A.P., Goadsby P.J. Modulation of nocioceptive transmission with calcitonin gene-related peptide receptor antagonists in the thalamus. Brain. 2010;133(9):2540–8. https://doi.org/10.1093/brain/awq224. PMID: 20802202Yu L.C., Weng X.H., Wang J.W., Lundeberg T. Involvement of calcitonin gene-related peptide and its receptor in anti-nociception in the periaqueductal grey of rats. Neurosci. Lett. 2003;349(1):1–4. https://doi.org/10.1016/s0304-3940 (03)00273-8. PMID: 12946572Yu L.C., Weng X.H., Wang J.W., Lundeberg T. Involvement of calcitonin gene-related peptide and its receptor in anti-nociception in the periaqueductal grey of rats. Neurosci. Lett. 2003;349(1):1–4. https://doi.org/10.1016/s0304-3940 (03)00273-8. PMID: 12946572Pozo-Rosich P., Storer R.J., Charbit A.R., Goadsby P.J. Periaqueductal gray calcitonin gene-related peptide modulates trigeminovascular neurons. Cephalalgia. 2015;35:1298–1307.Pozo-Rosich P., Storer R.J., Charbit A.R., Goadsby P.J. Periaqueductal gray calcitonin gene-related peptide modulates trigeminovascular neurons. Cephalalgia. 2015;35:1298–1307.Zhang Y., Zhang Y., Tian K., Wang Y., Fan X., Pan Q. et al. Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine. J. Headache Pain. 2020;21(1):72. Published 2020 Jun 10. https://doi.org/10.1186/s10194-020-01145-yZhang Y., Zhang Y., Tian K., Wang Y., Fan X., Pan Q. et al. Calcitonin gene-related peptide facilitates sensitization of the vestibular nucleus in a rat model of chronic migraine. J. Headache Pain. 2020;21(1):72. Published 2020 Jun 10. https://doi.org/10.1186/s10194-020-01145-yMason B.N., Kaiser E.A., Kuburas A., Loomis M.C., Latham J.A., Garcia-Martinez L.F. et al. Induction of Migraine-Like Photophobic Behavior in Mice by Both Peripheral and Central CGRP Mechanisms. J. Neurosci. 2017;37(1):204-216. https://doi.org/10.1523/JNEUROSCI.2967-16.2016Mason B.N., Kaiser E.A., Kuburas A., Loomis M.C., Latham J.A., Garcia-Martinez L.F. et al. Induction of Migraine-Like Photophobic Behavior in Mice by Both Peripheral and Central CGRP Mechanisms. J. Neurosci. 2017;37(1):204-216. https://doi.org/10.1523/JNEUROSCI.2967-16.2016Close L.N., Eftekhari S., Wang M., Charles A.C., Russo A.F. Cortical spreading depression as a site of origin for migraine: Role of CGRP. Cephalalgia. 2019;39(3):428–434. https://doi.org/10.1177/0333102418774299Close L.N., Eftekhari S., Wang M., Charles A.C., Russo A.F. Cortical spreading depression as a site of origin for migraine: Role of CGRP. Cephalalgia. 2019;39(3):428–434. https://doi.org/10.1177/0333102418774299Melo-Carrillo A., Schain A.J., Stratton J., Strassman A.M., Burstein R. Fremanezumab and its isotype slow propagation rate and shorten cortical recovery period but do not prevent occurrence of cortical spreading depression in rats with compromised blood-brain barrier. Pain. 2020;161(5):1037–1043. https://doi.org/10.1097/j.pain.0000000000001791Melo-Carrillo A., Schain A.J., Stratton J., Strassman A.M., Burstein R. Fremanezumab and its isotype slow propagation rate and shorten cortical recovery period but do not prevent occurrence of cortical spreading depression in rats with compromised blood-brain barrier. Pain. 2020;161(5):1037–1043. https://doi.org/10.1097/j.pain.0000000000001791Iyengar S., Ossipov M.H., Johnson K.W. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain. 2017;158(4):543–559. https://doi.org/10.1097/j.pain.0000000000000831. PMID: 28301400; PMCID: PMC5359791Iyengar S., Ossipov M.H., Johnson K.W. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain. 2017;158(4):543–559. https://doi.org/10.1097/j.pain.0000000000000831. PMID: 28301400; PMCID: PMC5359791Hay D.L., Walker C.S. CGRP and its receptors. Headache. 2017;57(4):625–636. https://doi.org/10.1111/head.13064. Epub 2017 Feb 24. PMID: 28233915Hay D.L., Walker C.S. CGRP and its receptors. Headache. 2017;57(4):625–636. https://doi.org/10.1111/head.13064. Epub 2017 Feb 24. PMID: 28233915Link A.S., Kuris A., Edvinsson L. Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system. J. Headache Pain. 2008;9(1):5–12. https://doi.org/10.1007/s10194-008-0011-4. Epub 2008 Jan 23. PMID: 18217201; PMCID: PMC2245994Link A.S., Kuris A., Edvinsson L. Treatment of migraine attacks based on the interaction with the trigemino-cerebrovascular system. J. Headache Pain. 2008;9(1):5–12. https://doi.org/10.1007/s10194-008-0011-4. Epub 2008 Jan 23. PMID: 18217201; PMCID: PMC2245994Negro A., Martelletti P. Gepants for the treatment of migraine. Expert Opin. Investig. Drugs. 2019;28(6):555–567. https://doi.org/10.1080/13543784.2019.1618830. Epub 2019 May 17. PMID: 31081399Negro A., Martelletti P. Gepants for the treatment of migraine. Expert Opin. Investig. Drugs. 2019;28(6):555–567. https://doi.org/10.1080/13543784.2019.1618830. Epub 2019 May 17. PMID: 31081399Juhasz G., Zsombok T., Jakab B., Nemeth J., Szolcsanyi J., Bagdy G. Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia. 2005;25(3):179–83. https://doi.org/10.1111/j.1468-2982.2005.00836.x. PMID: 15689192Juhasz G., Zsombok T., Jakab B., Nemeth J., Szolcsanyi J., Bagdy G. Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide (CGRP) concentration and migraine headache during nitroglycerin induced migraine attack. Cephalalgia. 2005;25(3):179–83. https://doi.org/10.1111/j.1468-2982.2005.00836.x. PMID: 15689192Ashina H., Schytz H.W., Ashina M. CGRP in Human Models of Migraine. Handb. Exp. Pharmacol. 2019;255:109–120. https://doi.org/10.1007/164_2018_128Ashina H., Schytz H.W., Ashina M. CGRP in Human Models of Migraine. Handb. Exp. Pharmacol. 2019;255:109–120. https://doi.org/10.1007/164_2018_128Deng H., Li G.G., Nie H., Feng Y.Y., Guo G.Y., Guo W.L. et al. Effi cacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine — an updated systematic review and meta-analysis. BMC Neurol. 2020;20(1):57. https://doi.org/10.1186/s12883-020-01633-3. PMID: 32061264; PMCID: PMC7023812Deng H., Li G.G., Nie H., Feng Y.Y., Guo G.Y., Guo W.L. et al. Effi cacy and safety of calcitonin-gene-related peptide binding monoclonal antibodies for the preventive treatment of episodic migraine — an updated systematic review and meta-analysis. BMC Neurol. 2020;20(1):57. https://doi.org/10.1186/s12883-020-01633-3. PMID: 32061264; PMCID: PMC7023812Tso A.R., Goadsby P.J. Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention? Curr. Treat. Options Neurol. 2017;19(8):27. https://doi.org/10.1007/s11940-017-0463-4. PMID: 28653227; PMCID: PMC5486583Tso A.R., Goadsby P.J. Anti-CGRP Monoclonal Antibodies: the Next Era of Migraine Prevention? Curr. Treat. Options Neurol. 2017;19(8):27. https://doi.org/10.1007/s11940-017-0463-4. PMID: 28653227; PMCID: PMC5486583Mitsikostas D.D., Reuter U. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr. Opin. Neurol. 2017;30(3):272–280. https://doi.org/10.1097/WCO.0000000000000438. PMID: 28240610Mitsikostas D.D., Reuter U. Calcitonin gene-related peptide monoclonal antibodies for migraine prevention: comparisons across randomized controlled studies. Curr. Opin. Neurol. 2017;30(3):272–280. https://doi.org/10.1097/WCO.0000000000000438. PMID: 28240610Goadsby P.J., Reuter U., Hallström 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. PMID: 29171821Goadsby P.J., Reuter U., Hallström 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. PMID: 29171821Tepper S., Ashina M., Reuter U., Brandes J.L., Doležil D., Silberstein S. et al. Safety and effi cacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425–434. https://doi.org/10.1016/S1474-4422 (17)30083-2. Epub 2017 Apr 28. PMID: 28460892Tepper S., Ashina M., Reuter U., Brandes J.L., Doležil D., Silberstein S. et al. Safety and effi cacy of erenumab for preventive treatment of chronic migraine: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Neurol. 2017;16(6):425–434. https://doi.org/10.1016/S1474-4422 (17)30083-2. Epub 2017 Apr 28. PMID: 28460892Wen L., Badgett R., Cornell J. Number needed to treat: a descriptor for weighing therapeutic options. Am. J. Health Syst. Pharm. 2005;62(19):2031-6. https://doi.org/10.2146/ajhp040558. PMID: 16174840Wen L., Badgett R., Cornell J. Number needed to treat: a descriptor for weighing therapeutic options. Am. J. Health Syst. Pharm. 2005;62(19):2031-6. https://doi.org/10.2146/ajhp040558. PMID: 16174840Sun H., Dodick D.W., Silberstein S., Goadsby P.J., Reuter U., Ashina M. et al. Safety and effi cacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):382–90. https://doi.org/10.1016/S1474-4422 (16)00019-3. Epub 2016 Feb 12. PMID: 26879279Sun H., Dodick D.W., Silberstein S., Goadsby P.J., Reuter U., Ashina M. et al. Safety and effi cacy of AMG 334 for prevention of episodic migraine: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2016;15(4):382–90. https://doi.org/10.1016/S1474-4422 (16)00019-3. Epub 2016 Feb 12. PMID: 26879279Dodick D.W., Ashina M., Brandes J.L., Kudrow D., LanteriMinet M., Osipova V. et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026–1037. https://doi.org/10.1177/0333102418759786. Epub 2018 Feb 22. PMID: 29471679Dodick D.W., Ashina M., Brandes J.L., Kudrow D., LanteriMinet M., Osipova V. et al. ARISE: A Phase 3 randomized trial of erenumab for episodic migraine. Cephalalgia. 2018;38(6):1026–1037. https://doi.org/10.1177/0333102418759786. Epub 2018 Feb 22. PMID: 29471679Goaj. 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. PMID: 29171821Goaj. 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. PMID: 29171821Reuter U., Goadsby P.J., Lanteri-Minet M., Wen S., HoursZesiger P., Ferrari M.D. et al. Effi cacy and tolerability of erenumab in patients with episodic migraine in whom two-tofour previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280–2287. doi: 10.1016/S0140-6736 (18)32534-0. Epub 2018 Oct 22. PMID: 30360965Reuter U., Goadsby P.J., Lanteri-Minet M., Wen S., HoursZesiger P., Ferrari M.D. et al. Effi cacy and tolerability of erenumab in patients with episodic migraine in whom two-tofour previous preventive treatments were unsuccessful: a randomised, double-blind, placebo-controlled, phase 3b study. Lancet. 2018;392(10161):2280–2287. doi: 10.1016/S0140-6736 (18)32534-0. Epub 2018 Oct 22. PMID: 30360965Dodick D.W., Silberstein S.D., Bigal M.E., Yeung P.P., Goadsby P.J., Blankenbiller T. et al. Eff ect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018;319(19):1999–2008. https://doi.org/10.1001/jama.2018.4853. PMID: 29800211; PMCID: PMC6583237Dodick D.W., Silberstein S.D., Bigal M.E., Yeung P.P., Goadsby P.J., Blankenbiller T. et al. Eff ect of Fremanezumab Compared With Placebo for Prevention of Episodic Migraine: A Randomized Clinical Trial. JAMA. 2018;319(19):1999–2008. https://doi.org/10.1001/jama.2018.4853. PMID: 29800211; PMCID: PMC6583237Bigal M.E., Edvinsson L., Rapoport A.M., Lipton R.B., Spierings E.L., Diener H.C. et al. Safety, tolerability, and effi - cacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14(11):1091–100. https://doi.org/10.1016/S1474-4422 (15)00245-8. Epub 2015 Sep 30. PMID: 26432181Bigal M.E., Edvinsson L., Rapoport A.M., Lipton R.B., Spierings E.L., Diener H.C. et al. Safety, tolerability, and effi - cacy of TEV-48125 for preventive treatment of chronic migraine: a multicentre, randomised, double-blind, placebo-controlled, phase 2b study. Lancet Neurol. 2015;14(11):1091–100. https://doi.org/10.1016/S1474-4422 (15)00245-8. Epub 2015 Sep 30. PMID: 26432181Dodick D.W., Goadsby P.J., Spierings E.L., Scherer J.C., Sweeney S.P., Grayzel D.S. Safety and effi cacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014;13(9):885–92. https://doi.org/10.1016/S1474-4422 (14)70128-0. Epub 2014 Aug 10. PMID: 25127173Dodick D.W., Goadsby P.J., Spierings E.L., Scherer J.C., Sweeney S.P., Grayzel D.S. Safety and effi cacy of LY2951742, a monoclonal antibody to calcitonin gene-related peptide, for the prevention of migraine: a phase 2, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2014;13(9):885–92. https://doi.org/10.1016/S1474-4422 (14)70128-0. Epub 2014 Aug 10. PMID: 25127173Skljarevski V., Matharu M., Millen B.A., Ossipov M.H., Kim B.K., Yang J.Y. Effi cacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442–1454. https://doi.org/10.1177/0333102418779543. Epub 2018 May 31. PMID: 29848108Skljarevski V., Matharu M., Millen B.A., Ossipov M.H., Kim B.K., Yang J.Y. Effi cacy and safety of galcanezumab for the prevention of episodic migraine: Results of the EVOLVE-2 Phase 3 randomized controlled clinical trial. Cephalalgia. 2018;38(8):1442–1454. https://doi.org/10.1177/0333102418779543. Epub 2018 May 31. PMID: 29848108Stauff er V.L., Dodick D.W., Zhang Q., Carter J.N., Ailani J., Conley R.R. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018;75(9):1080–1088. https://doi.org/10.1001/jamaneurol.2018.1212. Erratum in: JAMA Neurol. 2019;76(7):872. PMID: 29813147; PMCID: PMC6143119Stauff er V.L., Dodick D.W., Zhang Q., Carter J.N., Ailani J., Conley R.R. Evaluation of Galcanezumab for the Prevention of Episodic Migraine: The EVOLVE-1 Randomized Clinical Trial. JAMA Neurol. 2018;75(9):1080–1088. https://doi.org/10.1001/jamaneurol.2018.1212. Erratum in: JAMA Neurol. 2019;76(7):872. PMID: 29813147; PMCID: PMC6143119Skljarevski V., Oakes T.M., Zhang Q., Ferguson M.B., Martinez J., Camporeale A. et al. Eff ect of Diff erent Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention: A Randomized Clinical Trial. JAMA Neurol. 2018;75(2):187–193. https://doi.org/10.1001/jamaneurol.2017.3859. Erratum in: JAMA Neurol. 2018;75(2):260. PMID: 29255900; PMCID: PMC5838630Skljarevski V., Oakes T.M., Zhang Q., Ferguson M.B., Martinez J., Camporeale A. et al. Eff ect of Diff erent Doses of Galcanezumab vs Placebo for Episodic Migraine Prevention: A Randomized Clinical Trial. JAMA Neurol. 2018;75(2):187–193. https://doi.org/10.1001/jamaneurol.2017.3859. Erratum in: JAMA Neurol. 2018;75(2):260. PMID: 29255900; PMCID: PMC5838630Dodick D.W., Goadsby P.J., Silberstein S.D., Lipton R.B., Olesen J., Ashina M. et al. ALD403 study investigators. Safety and effi cacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014;13(11):1100–1107. https://doi.org/10.1016/S1474-4422 (14)70209-1. Epub 2014 Oct 5. PMID: 25297013Dodick D.W., Goadsby P.J., Silberstein S.D., Lipton R.B., Olesen J., Ashina M. et al. ALD403 study investigators. Safety and effi cacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine: a randomised, double-blind, placebo-controlled, exploratory phase 2 trial. Lancet Neurol. 2014;13(11):1100–1107. https://doi.org/10.1016/S1474-4422 (14)70209-1. Epub 2014 Oct 5. PMID: 25297013Zhu Y., Liu Y., Zhao J., Han Q., Liu L., Shen X. The effi cacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis. Neurol. Sci. 2018;39(12):2097–2106. https://doi.org/10.1007/s10072-018-3547-3. Epub 2018 Sep 4. PMID: 30182284Zhu Y., Liu Y., Zhao J., Han Q., Liu L., Shen X. The effi cacy and safety of calcitonin gene-related peptide monoclonal antibody for episodic migraine: a meta-analysis. Neurol. Sci. 2018;39(12):2097–2106. https://doi.org/10.1007/s10072-018-3547-3. Epub 2018 Sep 4. PMID: 30182284Lattanzi S., Brigo F., Trinka E., Vernieri F., Corradetti T., Dobran M. et al. Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Effi cacy and Safety. Drugs. 2019;79(4):417–431. https://doi.org/10.1007/s40265-019-01069-1. PMID: 30793254Lattanzi S., Brigo F., Trinka E., Vernieri F., Corradetti T., Dobran M. et al. Erenumab for Preventive Treatment of Migraine: A Systematic Review and Meta-Analysis of Effi cacy and Safety. Drugs. 2019;79(4):417–431. https://doi.org/10.1007/s40265-019-01069-1. PMID: 30793254Xu D., Chen D., Zhu L.N., Tan G., Wang H.J., Zhang Y. et al. Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine — a meta-analysis of randomized controlled trials. Cephalalgia. 2019;39(9):1164– 1179. https://doi.org/10.1177/0333102419829007. Epub 2019 Feb 21. PMID: 30789292Xu D., Chen D., Zhu L.N., Tan G., Wang H.J., Zhang Y. et al. Safety and tolerability of calcitonin-gene-related peptide binding monoclonal antibodies for the prevention of episodic migraine — a meta-analysis of randomized controlled trials. Cephalalgia. 2019;39(9):1164– 1179. https://doi.org/10.1177/0333102419829007. Epub 2019 Feb 21. PMID: 30789292Ashina M., Saper J., Cady R., Schaeffl er B.A., Biondi D.M., Hirman J. et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020;40(3):241–254. https://doi.org/10.1177/0333102420905132. Epub 2020 Feb 19. PMID: 32075406; PMCID: PMC7066477Ashina M., Saper J., Cady R., Schaeffl er B.A., Biondi D.M., Hirman J. et al. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1). Cephalalgia. 2020;40(3):241–254. https://doi.org/10.1177/0333102420905132. Epub 2020 Feb 19. PMID: 32075406; PMCID: PMC7066477Ashina M., Goadsby P.J., Reuter U., Silberstein S., Dodick D.W, Fei Xue et al. Long‐term effi cacy 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;00:1–10. https://doi.org/10.1111/ene.14715Ashina M., Goadsby P.J., Reuter U., Silberstein S., Dodick D.W, Fei Xue et al. Long‐term effi cacy 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;00:1–10. https://doi.org/10.1111/ene.14715Espinoza Giacomozzi A.R., Vindas A.P., da Silva Jr. A.A., Bordini C.A., Buonanotte C.F., de Paula Roesler C.A. et al. Latin American consensus on guidelines for chronic migraine treatment. Arq. Neuro-Psiquiatr. [online]. 2013;71(7) [cited 2021-02-20]:478-486. Available from: < http://www.scielo.br/scielo.php?script = sci_arttext&pid = S0004-282X2013000700478&lng = en&nrm = iso > . ISSN 0004-282X. http://dx.doi.org/10.1590/0004-282X20130066Espinoza Giacomozzi A.R., Vindas A.P., da Silva Jr. A.A., Bordini C.A., Buonanotte C.F., de Paula Roesler C.A. et al. Latin American consensus on guidelines for chronic migraine treatment. Arq. Neuro-Psiquiatr. [online]. 2013;71(7) [cited 2021-02-20]:478-486. Available from: < http://www.scielo.br/scielo.php?script = sci_arttext&pid = S0004-282X2013000700478&lng = en&nrm = iso > . ISSN 0004-282X. http://dx.doi.org/10.1590/0004-282X20130066Deneris A., Rosati Allen P., Hart Hayes E., Latendresse G. Migraines in Women: Current Evidence for Management of Episodic and Chronic Migraines. J. Midwifery Womens Health. 2017;62(3):270–285. https://doi.org/10.1111/jmwh.12626. Epub 2017 May 31. PMID: 28561915Deneris A., Rosati Allen P., Hart Hayes E., Latendresse G. Migraines in Women: Current Evidence for Management of Episodic and Chronic Migraines. J. Midwifery Womens Health. 2017;62(3):270–285. https://doi.org/10.1111/jmwh.12626. Epub 2017 May 31. PMID: 28561915Deen M., Correnti E., Kamm K., Kelderman T., Papetti L., Rubio-Beltrán E. et al. European Headache Federation School of Advanced Studies (EHF-SAS). Blocking CGRP in migraine patients — a review of pros and cons. J. Headache Pain. 2017;18(1):96. doi: 10.1186/s10194-017-0807-1. PMID: 28948500; PMCID: PMC5612904Deen M., Correnti E., Kamm K., Kelderman T., Papetti L., Rubio-Beltrán E. et al. European Headache Federation School of Advanced Studies (EHF-SAS). Blocking CGRP in migraine patients — a review of pros and cons. J. Headache Pain. 2017;18(1):96. doi: 10.1186/s10194-017-0807-1. PMID: 28948500; PMCID: PMC5612904Messlinger K. The big CGRP fl ood — sources, sinks and signalling sites in the trigeminovascular system. J. Headache Pain. 2018;19(1):22. https://doi.org/10.1186/s10194-018-0848-0. PMID: 29532195; PMCID: PMC5847494Messlinger K. The big CGRP fl ood — sources, sinks and signalling sites in the trigeminovascular system. J. Headache Pain. 2018;19(1):22. https://doi.org/10.1186/s10194-018-0848-0. PMID: 29532195; PMCID: PMC5847494Detke H.C., Goadsby P.J., Wang S., Friedman D.I., Selzler K.J., Aurora S.K. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211–e2221. https://doi.org/10.1212/WNL.0000000000006640. Epub 2018 Nov 16. PMID: 30446596; PMCID: PMC6329331Detke H.C., Goadsby P.J., Wang S., Friedman D.I., Selzler K.J., Aurora S.K. Galcanezumab in chronic migraine: The randomized, double-blind, placebo-controlled REGAIN study. Neurology. 2018;91(24):e2211–e2221. https://doi.org/10.1212/WNL.0000000000006640. Epub 2018 Nov 16. PMID: 30446596; PMCID: PMC6329331Silberstein S.D., Dodick D.W., Bigal M.E., Yeung P.P., Goadsby P.J., Blankenbiller T. et al. Fremanezumab for the Preventive Treatment of Chronic Migraine. N. Engl. J. Med. 2017;377(22):2113–2122. https://doi.org/10.1056/NEJMoa1709038. PMID: 29171818Silberstein S.D., Dodick D.W., Bigal M.E., Yeung P.P., Goadsby P.J., Blankenbiller T. et al. Fremanezumab for the Preventive Treatment of Chronic Migraine. N. Engl. J. Med. 2017;377(22):2113–2122. https://doi.org/10.1056/NEJMoa1709038. PMID: 29171818Hong P., Wu X., Liu Y. Calcitonin gene-related peptide monoclonal antibody for preventive treatment of episodic migraine: A meta analysis. Clin. Neurol. Neurosurg. 2017;154:74–78. https://doi.org/10.1016/j.clineuro.2017.01.009. Epub 2017 Jan 22. PMID: 28129635Hong P., Wu X., Liu Y. Calcitonin gene-related peptide monoclonal antibody for preventive treatment of episodic migraine: A meta analysis. Clin. Neurol. Neurosurg. 2017;154:74–78. https://doi.org/10.1016/j.clineuro.2017.01.009. Epub 2017 Jan 22. PMID: 28129635

The authors declare that there are no conflicts of interest present.