medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/2079-701X-2019-9-56-62medsovet-3035Research ArticleДЕМИЕЛИНИЗИРУЮЩИЕ ЗАБОЛЕВАНИЯDEMYELINATING DISEASESКлиническая эффективность и безопасность алемтузумаба в постмаркетинговой практикеClinical efficacy and safety of alemtuzumab in postmarketing practiceХачановаН. В.KhachanovaN. V.

к.м.н., профессор кафедры неврологии, нейрохирургии и медицинской генетики Федерального государственного бюджетного образовательного учреждения высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации.

Cand. of Sci. (Med.). Professor of Chair for Neurology, Neurosurgery and Medical Genetics, Federal State Budgetary Educational Institution of Higher Education «N.I.Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian Federation.

voroba.nat@mail.ruФедеральное государственное бюджетное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской Федерации.РоссияFederal State Budgetary Educational Institution of Higher Education Russian National Research Medical University named after N.I. Pirogov of the Ministry of Health of the Russian Federation.Russian Federation201911062019095662Copyright © Хачанова Н.В., 20192019Хачанова Н.В.Khachanova N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/3035

Клинические исследования подтверждают эффективность алемтузумаба в терапии рассеянного склероза не только по традиционным показателям, но и по комбинированным параметрам, таким как NEDA (no evidence of disease activity – отсутствие признаков активности болезни). Однако доказанная эффективность препарата и удобная схема лечения уравновешиваются возможностью развития серьезных нежелательных явлений. В связи с этим необходимо повышать осведомленность врачей как о потенциальных преимуществах терапии алемтузумабом, так и об особенностях его профиля безопасности. Настоящий обзор представляет собой анализ исследований реальной клинической практики применения препарата в Европе, США и других регионах. Полученная информация поможет врачам правильно назначать и проводить лечение алемтузумабом, а также обеспечивать эффективный мониторинг безопасности с целью своевременного выявления нежелательных явлений и сохранения максимальной пользы терапии для пациента.

Clinical trials confirm alemtuzumab efficacy for multiple sclerosis treatment in terms of both conventional measures and combined criteria such as NEDA (no evidence of disease activity). However, established drug efficacy and convenient dosing schedule are balanced by the risk of serious adverse events. Therefore, it is necessary to inform physicians about the benefits of alemtuzumab therapy along with the pattern of its safety profile.The present review provides the analysis of alemtuzumab real-world studies in Europe, USA and other parts of the world. The information obtained can help physicians to prescribe and administer the drug properly and to perform effective safety monitoring for early detection of adverse events and saving the maximum treatment benefit for the patient.

алемтузумабданные реальной клинической практикипрепаратыизменяющие течение рассеянного склерозарассеянный склерозalemtuzumabreal-world datadisease-modifying therapymultiple sclerosisReferencesBielekova B., Becker B.L. Monoclonal antibodies in MS: mechanisms of action. Neurology.2010;74(Suppl 1):S31-S40. DOI: 10.1212/WNL.0b013e3181c97ed3.Bielekova B., Becker B.L. Monoclonal antibodies in MS: mechanisms of action. Neurology.2010;74(Suppl 1):S31-S40. DOI: 10.1212/WNL.0b013e3181c97ed3.Thompson S.A., Jones J.L., Cox A.L. et al. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J. Clin. Immunol. 2010;30(1):99-105. doi: 10.1007/s10875-009-9327-3.Thompson S.A., Jones J.L., Cox A.L. et al. B-cell reconstitution and BAFF after alemtuzumab (Campath-1H) treatment of multiple sclerosis. J. Clin. Immunol. 2010;30(1):99-105. doi: 10.1007/s10875-009-9327-3.Cox A.L., Thompson S.A., Jones J.L. et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur. J. Immunol.2005;35(11):3332-42. doi: 10.1002/eji.200535075.Cox A.L., Thompson S.A., Jones J.L. et al. Lymphocyte homeostasis following therapeutic lymphocyte depletion in multiple sclerosis. Eur. J. Immunol.2005;35(11):3332-42. doi: 10.1002/eji.200535075.Ruck T., Afzali A.M., Lukat K.F. et al. ALAIN01 – Alemtuzumab in autoimmune inflammatory neurodegeneration: mechanisms of action and neuroprotective potential. BMC Neurology.2016;14:34. doi: 10.1186/s12883-016-0556-9.Ruck T., Afzali A.M., Lukat K.F. et al. ALAIN01 – Alemtuzumab in autoimmune inflammatory neurodegeneration: mechanisms of action and neuroprotective potential. BMC Neurology.2016;14:34. doi: 10.1186/s12883-016-0556-9.Hu Y., Turner M.J., Shields J., et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology.2009;128(2):260-70. doi: 10.1111/j.1365-2567.2009.03115.x.Hu Y., Turner M.J., Shields J., et al. Investigation of the mechanism of action of alemtuzumab in a human CD52 transgenic mouse model. Immunology.2009;128(2):260-70. doi: 10.1111/j.1365-2567.2009.03115.x.Coles A.J., Compston D.A., Selmaj K.W., et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N. Engl. J.Med. 2008;359:1786–1801. doi: 10.1056/NEJMoa0802670.Coles A.J., Compston D.A., Selmaj K.W., et al. Alemtuzumab vs. interferon beta-1a in early multiple sclerosis. N. Engl. J.Med. 2008;359:1786–1801. doi: 10.1056/NEJMoa0802670.Coles A.J., Twyman C.L., Arnold D.L., et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet.2012;380:1829–1839. doi: 10.1016/S0140-6736(12)61768-1.Coles A.J., Twyman C.L., Arnold D.L., et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet.2012;380:1829–1839. doi: 10.1016/S0140-6736(12)61768-1.Cohen J.A., Coles A.J., Arnold D.L., et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing- remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819–1828. doi: 10.1016/S0140-6736(12)61769-3.Cohen J.A., Coles A.J., Arnold D.L., et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing- remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380:1819–1828. doi: 10.1016/S0140-6736(12)61769-3.Coles A.J., Fox E., Vladic A., et. al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012; 8(14):1069–1078. doi: 10.1212/WNL.0000000000004354.Coles A.J., Fox E., Vladic A., et. al. Alemtuzumab more effective than interferon β-1a at 5-year follow-up of CAMMS223 clinical trial. Neurology. 2012; 8(14):1069–1078. doi: 10.1212/WNL.0000000000004354.Havrdova E., Arnold D.L., Cohen J.A., et al. Alemtuzumab CARE-MS I 5-year follow-up: durable efficacy in the absence of continuous MS therapy. Neurology. 2017;89(11):1107–1116. doi: 10.1212/WNL.0000000000004313.Havrdova E., Arnold D.L., Cohen J.A., et al. Alemtuzumab CARE-MS I 5-year follow-up: durable efficacy in the absence of continuous MS therapy. Neurology. 2017;89(11):1107–1116. doi: 10.1212/WNL.0000000000004313.Arnold D.L., Fisher E., Brinar V.V., et al. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS. Neurology. 2016;87(14):1464–1472. doi: 10.1212/WNL.0000000000003169.Arnold D.L., Fisher E., Brinar V.V., et al. Superior MRI outcomes with alemtuzumab compared with subcutaneous interferon β-1a in MS. Neurology. 2016;87(14):1464–1472. doi: 10.1212/WNL.0000000000003169.Coles A.J., Boyko A.N., Cohen J.A., et al. Alemtuzumab provides durable improvements in clinical outcomes in treatment-naive patients with active relapsing-remitting multiple sclerosis over 6 years in the absence of continuous treatment (CARE-MS I). Mult. Scler.2016;22:P213.Coles A.J., Boyko A.N., Cohen J.A., et al. Alemtuzumab provides durable improvements in clinical outcomes in treatment-naive patients with active relapsing-remitting multiple sclerosis over 6 years in the absence of continuous treatment (CARE-MS I). Mult. Scler.2016;22:P213.Fox E.J., Alroughani R., Brassat D., et al. Efficacy of alemtuzumab is durable over 6 years in patients with active relapsing-remitting multiple sclerosis and an inadequate response to prior therapy in the absence of continuous treatment (CARE-MS II). Mult. Scler. 2016;22:P1150.Fox E.J., Alroughani R., Brassat D., et al. Efficacy of alemtuzumab is durable over 6 years in patients with active relapsing-remitting multiple sclerosis and an inadequate response to prior therapy in the absence of continuous treatment (CARE-MS II). Mult. Scler. 2016;22:P1150.Giovannoni G., Cohen J.A., Coles A.J., et al. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology.2016;87(19):1985–1992. doi: 0.1212/WNL.0000000000003319.Giovannoni G., Cohen J.A., Coles A.J., et al. Alemtuzumab improves preexisting disability in active relapsing-remitting MS patients. Neurology.2016;87(19):1985–1992. doi: 0.1212/WNL.0000000000003319.Horakova D., Boster A., Ziemssen T., et al. Patients who received alemtuzumab in CAREMS I or II show a low rate of conversion from relapsing-remitting MS to secondary progressive MS through 6 years. Neurology. 2017;88(Suppl.16):P4.407.Horakova D., Boster A., Ziemssen T., et al. Patients who received alemtuzumab in CAREMS I or II show a low rate of conversion from relapsing-remitting MS to secondary progressive MS through 6 years. Neurology. 2017;88(Suppl.16):P4.407.Ziemssen T., Thomas K. Alemtuzumab in longterm treatment of relapsing-remitting multiple sclerosis: an update on clinical trial evidence and data from the real world. Ther. Adv. Neurol. Disord.2017;10(10):343–359. doi: 10.1177/1756285617722706.Ziemssen T., Thomas K. Alemtuzumab in longterm treatment of relapsing-remitting multiple sclerosis: an update on clinical trial evidence and data from the real world. Ther. Adv. Neurol. Disord.2017;10(10):343–359. doi: 10.1177/1756285617722706.Zivadinov R., Bergsland N., Dolezal O. et al. Evolution of Cortical and Thalamus Atrophy and Disability Progression in Early RelapsingRemitting MS during 5 Years. AJNR Am. J. Neuroradiol.2013;34:1931–39. doi: 10.3174/ajnr.A3503.Zivadinov R., Bergsland N., Dolezal O. et al. Evolution of Cortical and Thalamus Atrophy and Disability Progression in Early RelapsingRemitting MS during 5 Years. AJNR Am. J. Neuroradiol.2013;34:1931–39. doi: 10.3174/ajnr.A3503.Zivadinov R., Sepcic J., Nasuelli D. Et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsingremitting multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 2001;70(6):773-80. doi: 10.1136/jnnp.70.6.773.Zivadinov R., Sepcic J., Nasuelli D. Et al. A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsingremitting multiple sclerosis. J. Neurol. Neurosurg. Psychiatry. 2001;70(6):773-80. doi: 10.1136/jnnp.70.6.773.Selmaj K., Habek M., Bass A., et al. Efficacy and safety of alemtuzumab in patients with RRMS is durable over 10 years: follow-up from the CAMMS223 study. Mult. Scler.2016;22:P679.Selmaj K., Habek M., Bass A., et al. Efficacy and safety of alemtuzumab in patients with RRMS is durable over 10 years: follow-up from the CAMMS223 study. Mult. Scler.2016;22:P679.Dayan C., Cuker A., LaGanke C., et al. Autoimmunity in patients treated with alemtuzumab for relapsing-remitting multiple sclerosis: 6-year follow-up of the CARE-MS studies. Mult. Scler.2016;22:168.Dayan C., Cuker A., LaGanke C., et al. Autoimmunity in patients treated with alemtuzumab for relapsing-remitting multiple sclerosis: 6-year follow-up of the CARE-MS studies. Mult. Scler.2016;22:168.Kim H., Lee E.J., Kim S.K., et al. Efficacy and safety of alemtuzumab in Korean multiple sclerosis patients. Multiple Sclerosis and Related Disorders. 2019;30: 247–251. doi: 10.1016/j.msard.2019.03.001.Kim H., Lee E.J., Kim S.K., et al. Efficacy and safety of alemtuzumab in Korean multiple sclerosis patients. Multiple Sclerosis and Related Disorders. 2019;30: 247–251. doi: 10.1016/j.msard.2019.03.001.Coles A.J., Cohen J.A., Fox E.J., et. al. Alemtuzumab CARE- MS II 5-year follow-up: efficacy and safety findings. Neurology.2017;89(11):1117–1126. doi: 10.1212/WNL.0000000000004354.Coles A.J., Cohen J.A., Fox E.J., et. al. Alemtuzumab CARE- MS II 5-year follow-up: efficacy and safety findings. Neurology.2017;89(11):1117–1126. doi: 10.1212/WNL.0000000000004354.Khalili E., Venning B., Boggild M., et al. 082 Real world experience of treating multiple sclerosis with alemtuzumab. J. Neurol. Neurosurg. Psychiatry.2018;89:A33. doi: 10.1136/jnnp-2018-ANZAN.81.Khalili E., Venning B., Boggild M., et al. 082 Real world experience of treating multiple sclerosis with alemtuzumab. J. Neurol. Neurosurg. Psychiatry.2018;89:A33. doi: 10.1136/jnnp-2018-ANZAN.81.Prosperini L., Annovazzi P., Boffa L. et al. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month realworld study.J. Neurol.2018;265:2851. doi: 10.1007/s00415-018-9070-x.Prosperini L., Annovazzi P., Boffa L. et al. No evidence of disease activity (NEDA-3) and disability improvement after alemtuzumab treatment for multiple sclerosis: a 36-month realworld study.J. Neurol.2018;265:2851. doi: 10.1007/s00415-018-9070-x.EMA. (European Medicines Agency). EMA confirms recommendations to minimize risk of brain infection PML with Tysabri. 2016.EMA. (European Medicines Agency). EMA confirms recommendations to minimize risk of brain infection PML with Tysabri. 2016.Frau J., Coghe G., Lorefice L. et al. Efficacy and safety of alemtuzumab in a real-life cohort of patients with multiple sclerosis. J. Neurol.2019. doi: 10.1007/s00415-019-09272-6.Frau J., Coghe G., Lorefice L. et al. Efficacy and safety of alemtuzumab in a real-life cohort of patients with multiple sclerosis. J. Neurol.2019. doi: 10.1007/s00415-019-09272-6.Wiendl H., Calabresi P.A., Meuth S.G. Defining response profiles after alemtuzumab: rare paradoxical disease exacerbation. Neurology.2018;90(7):309–311. doi: 10.1212/WNL.0000000000004969.Wiendl H., Calabresi P.A., Meuth S.G. Defining response profiles after alemtuzumab: rare paradoxical disease exacerbation. Neurology.2018;90(7):309–311. doi: 10.1212/WNL.0000000000004969.Blasco M.R., Ramos A., Malo C.G., et al. Acute pneumonitis and pericarditis related to alemtuzumab therapy in relapsing-remitting multiple sclerosis. J. Neurol.2017;264(1):168–169. doi: 10.1007/s00415-016-8306-x.Blasco M.R., Ramos A., Malo C.G., et al. Acute pneumonitis and pericarditis related to alemtuzumab therapy in relapsing-remitting multiple sclerosis. J. Neurol.2017;264(1):168–169. doi: 10.1007/s00415-016-8306-x.Whiteside D., Barth S., Datta A., et al. Pneumonitis secondary to alemtuzumab in a patient with multiple sclerosis – A non-infectious cause of breathlessness. Multiple Sclerosis and Related Disorders.2018;22:139–140. doi: 10.1016/j.msard.2018.04.002.Whiteside D., Barth S., Datta A., et al. Pneumonitis secondary to alemtuzumab in a patient with multiple sclerosis – A non-infectious cause of breathlessness. Multiple Sclerosis and Related Disorders.2018;22:139–140. doi: 10.1016/j.msard.2018.04.002.Willis M.D., Harding K.E., Pickersgill T.P., et al. Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort. Multiple Sclerosis Journal.2016;22(9):1215–1223. doi: 10.1177/1352458515614092.Willis M.D., Harding K.E., Pickersgill T.P., et al. Alemtuzumab for multiple sclerosis: Long term follow-up in a multi-centre cohort. Multiple Sclerosis Journal.2016;22(9):1215–1223. doi: 10.1177/1352458515614092.Le Page E., Deburghgraeve V., Lester MA. et al. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study. J. Neurol.2015;262(4):1024-34. doi: doi: 10.1007/s00415-015-7653-3.Le Page E., Deburghgraeve V., Lester MA. et al. Alemtuzumab as rescue therapy in a cohort of 16 aggressive multiple sclerosis patients previously treated by Mitoxantrone: an observational study. J. Neurol.2015;262(4):1024-34. doi: doi: 10.1007/s00415-015-7653-3.La Ganke C., Adcock A. Clinical outcomes of 200 multiple sclerosis patients switching from natalizumab to alemtuzumab in a single United States MS center. Neurology.2016;86:P3.117.La Ganke C., Adcock A. Clinical outcomes of 200 multiple sclerosis patients switching from natalizumab to alemtuzumab in a single United States MS center. Neurology.2016;86:P3.117.Huhn K., Bayas A., Doerck S., et al. Alemtuzumab as rescue therapy in a cohort of 50 relapsing–remitting MS patients with breakthrough disease on fingolimod: a multicenter observational study. J. Neurol. 2018;265(7):1521-1527.Huhn K., Bayas A., Doerck S., et al. Alemtuzumab as rescue therapy in a cohort of 50 relapsing–remitting MS patients with breakthrough disease on fingolimod: a multicenter observational study. J. Neurol. 2018;265(7):1521-1527.

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