medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2026-304medsovet-10410Research ArticleДЕМИЕЛИНИЗИРУЮЩИЕ ЗАБОЛЕВАНИЯDEMYELINATING DISEASESРасширение показаний кладрибина в таблетках при рассеянном склерозе: от раннего назначения наивным пациентам к возможности проведения повторных курсов терапии спустя 4 года инициации лечения кладрибиномExpanding the indications of cladribine tablets for multiple sclerosis: From early use in treatment-naive patients to the possibility of retreatment courses after 4 years of cladribine initiation therapyhttps://orcid.org/0000-0003-2676-452XПоповаЕ. В.PopovaE. V.

Попова Екатерина Валерьевна - д.м.н., заведующая межокружным отделением рассеянного склероза.

4127015, Москва, ул. Писцовая, д. 10

Ekaterina V. Popova - Dr. Sci. (Med.), Head of the Interdistrict Department of Multiple Sclerosis.

10, Pistsovaya St., Moscow, 127015

ani_retake1@mail.ruhttps://orcid.org/0000-0002-4943-4630ХачановаН. В.KhachanovaN. V.

Хачанова Наталья Валерьевна - к.м.н., профессор кафедры неврологии, нейрохирургии и медицинской генетики, РНИМУ имени Н.И. Пирогова; врач-невролог межокружного отделения рассеянного склероза, ГКБ №24;

117513, Москва, ул. Островитянова, д. 1; 127015, Москва, ул. Писцовая, д. 10

Natalia V. Khachanova - Cand. Sci. (Med.), Professor of the Department of Neurology, Neurosurgery and Medical Genetics, Pirogov Russian NRMU; Neurologist of the Interdistrict Department of Multiple Sclerosis, CCH No. 24.

1, Ostrovityanov St., Moscow, 117513; 10, Pistsovaya St., Moscow, 127015

voroba.nat@mail.ruhttps://orcid.org/0000-0002-1454-1807АброськинаМ. В.AbroskinaM. V.

Аброськина Мария Васильевна - к.м.н., доцент кафедры нервных болезней с курсом последипломного образования, Красноярский ГМУ имени профессора В.Ф. Войно-Ясенецкого; руководитель Центра рассеянного склероза, ККБ.

660022, Красноярск, ул. Партизана Железняка, д. 1; 660049, Красноярск, ул. Карла Маркса, д. 34б

Mariia V. Abroskina - Cand. Sci. (Med.), Associate Professor of the Department of Nervous Diseases with a Course of Postgraduate Education, VoinoYasenetsky Krasnoyarsk SMU; Head of the Multiple Sclerosis Center, RCH.

1, Partizan Zheleznyak St., Krasnoyarsk, 660022; 34b, Karl Marx St., Krasnoyarsk, 660049

mabroskina@yandex.ruhttps://orcid.org/0000-0002-8294-0893ДавыдовскаяМ. В.DavydovskayaM. V.

Давыдовская Мария Вафаевна - д.м.н., заместитель главного внештатного специалиста невролога Департамента здравоохранения города Москвы, заместитель директора по науке, Научно-практический центр клинико-экономического анализа Министерства здравоохранения Московской области; врач-невролог межокружного отделения рассеянного склероза, ГКБ №24;

143403, Московская обл., Красногорск, ул. Карбышева, д. 4а; 127015, Москва, ул. Писцовая, д. 10

Maria V. Davydovskaya - Dr. Sci. (Med.), Deputy Chief Freelance Neurologist of the Moscow Department of Health, Deputy Director for Science, Scientific and Practical Center for Clinical and Economic Analysis of the Ministry of Health of the Moscow Region; Neurologist of the Interdistrict Department of Multiple Sclerosis, CCH No. 24.

4a, Karbyshev St., Krasnogorsk, Moscow Region, 143403; 10, Pistsovaya St., Moscow, 127015

davydovskaya@gmail.ruhttps://orcid.org/0000-0002-8006-237XЕвдошенкоЕ. П.EvdoshenkoE. P.

Евдошенко Евгений Петрович - к.м.н., руководитель Городского центра по лечению рассеянного склероза.

197110, Санкт-Петербург, проспект Динамо, д. 3

Evgeniy P. Evdoshenko - Cand. Sci. (Med.), Director of the City Center for Multiple Sclerosis.

3, Dinamo Ave., St Petersburg, 197110

e.evdoshenko@centrems.comhttps://orcid.org/0000-0001-7439-2690ШумилинаМ. В.ShumilinaM. V.

Шумилина Мария Васильевна - к.м.н., руководитель поликлинического отделения Городского центра по лечению рассеянного склероза.

197110, Санкт-Петербург, проспект Динамо, д. 3

Maria V. Shumilina - Cand. Sci. (Med.), Head of the Outpatient Department, City Center for Multiple Sclerosis.

3, Dinamo Ave., St Petersburg, 197110

maria_shumillina@yahoo.comhttps://orcid.org/0000-0002-7938-3782КоробкоД. С.KorobkoD. S.

Коробко Денис Сергеевич - к.м.н., врач-невролог, заведующий областным центром рассеянного склероза и других аутоиммунных заболеваний нервной системы, Государственная Новосибирская ОКБ; ассистент кафедры неврологии, Новосибирский государственный медицинский университет;

630087, Новосибирск, ул. Немировича-Данченко, д. 130; 630091, Новосибирск, Красный проспект, д. 52

Denis S. Korobko - Cand. Sci. (Med.), Head of the Regional Center for Multiple Sclerosis and Other Autoimmune Diseases of the Nervous System, State Novosibirsk RCH; Assistant of the Department of Clinical Neurology and Neurogeriatrics, Novosibirsk SMU.

126, Nemirovich-Danchenko St., 630087, Novosibirsk; 52, Krasny Ave., Novosibirsk, 630091

Denis.s.korobko@gmail.comhttps://orcid.org/0000-0003-4489-3800НиловА. И.NilovA. I.

Нилов Алексей Иванович - врач-невролог высшей категории.

443095, Самара, ул. Ташкентская, д. 159

Aleksej I. Nilov - Neurologist of the Highest Category.

159, Tashkentskaya St., Samara, 443095

colueram@yandex.ruhttps://orcid.org/0009-0004-8742-6182СуторминМ. В.SutorminM. V.

Сутормин Максим Викторович, к.м.н., главный внештатный специалист-невролог Министерства здравоохранения Российской Федерации по ЦФО, главный внештатный специалист-невролог Московской области, руководитель службы неврологии и реабилитации.

129110, Москва, ул. Щепкина, д. 61/2

Maxim V. Sutormin - Chief Freelance Neurologist of the Ministry of Health of the Russian Federation for the Central Federal District, Chief Freelance Specialist Neurologist of the Moscow Region, Head of the Neurology and Rehabilitation Service.

61/2, Schepkin St., Moscow, 129110

nevrokgb@yandex.ruhttps://orcid.org/0000-0001-9680-7308ТринитатскийЮ. В.TrinitatskiyYu. V.

Тринитатский Юрий Владимирович - д.м.н., профессор, врач высшей категории, заслуженный врач Российской Федерации, директор Центра неврологии.

344015, Ростов-на-Дону, ул. Благодатная, д. 170

Yuriy V. Trinitatskiy - Dr. Sci. (Med.), Professor, Doctor of the Highest Category, Honored Doctor of the Russian Federation, Director of the Center for Neurology.

170, Blagodatnaya St., Rostov-on-Don, 344015

trinitatskiy.rrch@gmail.comhttps://orcid.org/0000-0003-0402-7430ШейкоГ. Е.SheikoG. E.

Шейко Геннадий Евгеньевич - к.м.н., главный внештатный невролог, доцент кафедры медицинской реабилитации.

603005, Нижний Новгород, пл. Минина и Пожарского, д. 10/1

Gennadii E. Sheiko - Cand. Sci. (Med.), Chief Freelance Neurologist of Nizhny Novgorod, Associate Professor of the Department of Medical Rehabilitation.

10/1, Minin and Pozharsky Sq., Nizhny Novgorod, 603005

sheikogennadii@yandex.ruГородская клиническая больница №24РоссияCity Clinical Hospital No. 24 Moscow Healthcare DepartmentRussian FederationГородская клиническая больница №24; Российский национальный исследовательский медицинский университет имени Н.И. ПироговаРоссияCity Clinical Hospital No. 24 Moscow Healthcare Department; Pirogov Russian National Research Medical UniversityRussian FederationКрасноярский государственный медицинский университет имени профессора В.Ф. Войно-Ясенецкого; Краевая клиническая больницаРоссияVoino-Yasenetsky Krasnoyarsk State Medical University; Regional Clinical HospitalRussian FederationГородская клиническая больница №24; Научно-практический центр клинико-экономического анализа Министерства здравоохранения Московской областиРоссияCity Clinical Hospital No. 24 Moscow Healthcare Department; Scientific and Practical Center for Clinical and Economic Analysis of the Ministry of Health of the Moscow RegionRussian FederationГородская клиническая больница №31РоссияСity Clinical Hospital No. 31Russian FederationГосударственная Новосибирская областная клиническая больница; Новосибирский государственный медицинский университетРоссияNovosibirsk State Regional Clinical Hospital; Novosibirsk State Medical UniversityRussian FederationСамарская областная клиническая больница имени В.Д. СередавинаРоссияSamara Regional Clinical Hospital named after V.D. SeredavinRussian FederationМосковский областной научно-исследовательский клинический институт имени М.Ф. ВладимирскогоРоссияMoscow Regional Research and Clinical Institute (“MONIKI”)Russian FederationРостовская областная клиническая больницаРоссияRostov Regional Clinical HospitalRussian FederationПриволжский исследовательский медицинский университетРоссияPrivolzhsky Research Medical UniversityRussian Federation202614092026012138148Copyright © Попова Е.В., Хачанова Н.В., Аброськина М.В., Давыдовская М.В., Евдошенко Е.П., Шумилина М.В., Коробко Д.С., Нилов А.И., Сутормин М.В., Тринитатский Ю.В., Шейко Г.Е., 20262026Попова Е.В., Хачанова Н.В., Аброськина М.В., Давыдовская М.В., Евдошенко Е.П., Шумилина М.В., Коробко Д.С., Нилов А.И., Сутормин М.В., Тринитатский Ю.В., Шейко Г.Е.Popova E.V., Khachanova N.V., Abroskina M.V., Davydovskaya M.V., Evdoshenko E.P., Shumilina M.V., Korobko D.S., Nilov A.I., Sutormin M.V., Trinitatskiy Y.V., Sheiko G.E.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/10410

Аутоиммунные заболевания являются распространенными клиническими состояниями, возникающими в результате аномального иммунного ответа на собственные структуры организма. Большинство существующих иммуномодулирующих препаратов способно подавлять аутоиммунные реакции до тех пор, пока они применяются, но они не нацелены на аутореактивную иммунологическую память и не могут отключить лежащие в основе механизмы, чтобы вызвать ремиссию без терапии. За последнее десятилетие возрос интерес к высокоэффективной терапии иммунной реконституции, с помощью которой возможно транзиторно или стойко провоцировать ре-программирование иммунной системы. Кладрибин (2-хлоро-дезоксиаденозин) в таблетках относится к группе препаратов ТИР при рецидивирующем рассеянном склерозе, терапия которым включает в себя два коротких курса лечения в течение 1-го и 2-го года. Большинство пациентов достигают устойчивой эффективности при применении кладрибина, но у небольшой части пациентов может наблюдаться новая активность заболевания, требующая от лечащего врача принятия решения в отношении ранее выбранной стратегии терапии. С тех пор, как более 5 лет назад кладрибин в таблетках был одобрен Европейским союзом, в США и России, число публикаций, посвященных анализу данных рутинной практики, неуклонно возрастает. Целью публикации является представление результатов работы экспертного совета, проведенного в феврале 2026 г. Участниками совета экспертов выработаны дальнейшие рекомендации по назначению препарата терапевтически наивным пациентам с рецидивирующим рассеянным склерозом, применению при вторично-прогрессирующем рассеянном склерозе с обострениями, алгоритмы ведения пациентов с рецидивирующим рассеянным склерозом с возобновлением активности заболевания после стартовых 2 курсов терапии кладрибином при последующем наблюдении, обсуждены профили пациентов, у которых смена терапии на кладрибин в таблетках рассматривается в качестве опции, снижающей риски постоянной иммуносупрессии.

Autoimmune disorders are common clinical conditions that result from an abnormal immune response to the body’s own structures. Most existing immunomodulatory drugs for multiple sclerosis (MS) therapy are capable of suppressing autoimmune reactions as long as they are used, but they do not target autoreactive immunological memory and cannot disable the underlying mechanisms to induce remission without therapy. Over the past decade, there has been an increased interest in highly effective immune reconstruction therapy (IRT), which can transiently or persistently provoke the immune system resetting. Cladribine (2-chloro-deoxyadenosine) in tablets belongs to the group of IRT drugs for relapsing multiple sclerosis (RMS), which therapy consists of two short courses of treatment during the 1st and 2nd year. Most patients achieve sustained efficacy with the use of cladribine, but a small proportion of patients may experience new disease activity that requires the treating physician to make a decision regarding a previously chosen treatment strategy. Since cladribine tablets were approved by the European Union, USA and Russia more than 5 years ago, the number of publications devoted to the analysis of real-world practice has been steadily increasing. The purpose of this publication is to present the results of Expert Council conducted in February 2026. The participants of the expert council developed further recommendations for the administration of the drug to therapeutically naive patients with relapsing-remitting MS, in secondary progressive MS with exacerbations, algorithms for managing patients with RMS with disease activity reactivation after the initial 2 courses of therapy with cladribine and subsequent follow-up, and discussed the profiles of patients in whom switching to cladribine tablets is considered as an option that reduces the risks of prolonged immunosuppression.

кладрибинэффективностьбезопасностьпрофили пациентовповторное лечениенаблюдениеиммуносупрессияcladribineeffectivenesssafetypatient profilesretreatmentmonitoringimmunosupressionReferencesRammohan K, Coyle PK, Sylvester E, Galazka A, Dangond F, Grosso M, Leist TP. The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review. Drugs. 2020;80(18):1901–1928. https://doi.org/10.1007/s40265-020-01422-9.Rammohan K, Coyle PK, Sylvester E, Galazka A, Dangond F, Grosso M, Leist TP. The Development of Cladribine Tablets for the Treatment of Multiple Sclerosis: A Comprehensive Review. Drugs. 2020;80(18):1901–1928. https://doi.org/10.1007/s40265-020-01422-9.Baker D, Pryce G, Herrod SS, Schmierer K. Potential mechanisms of action related to the efficacy and safety of cladribine. Mult Scler Relat Disord. 2019;30:176–186. https://doi.org/10.1016/j.msard.2019.02.018.Baker D, Pryce G, Herrod SS, Schmierer K. Potential mechanisms of action related to the efficacy and safety of cladribine. Mult Scler Relat Disord. 2019;30:176–186. https://doi.org/10.1016/j.msard.2019.02.018.Leist TP, Weissert R. Cladribine: mode of action and implications for treatment of multiple sclerosis. Clin Neuropharmacol. 2011;34(1):28–35. https://doi.org/10.1097/WNF.0b013e318204cd90.Leist TP, Weissert R. Cladribine: mode of action and implications for treatment of multiple sclerosis. Clin Neuropharmacol. 2011;34(1):28–35. https://doi.org/10.1097/WNF.0b013e318204cd90.Sigal DS, Miller HJ, Schram ED, Saven A. Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010;116(16):2884–2896. https://doi.org/10.1182/blood-2010-02-246140.Sigal DS, Miller HJ, Schram ED, Saven A. Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010;116(16):2884–2896. https://doi.org/10.1182/blood-2010-02-246140.Giovannoni G, Mathews J. Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician’s Review. Neurol Ther. 2022;11(2):571–595. https://doi.org/10.1007/s40120-022-00339-7.Giovannoni G, Mathews J. Cladribine Tablets for Relapsing-Remitting Multiple Sclerosis: A Clinician’s Review. Neurol Ther. 2022;11(2):571–595. https://doi.org/10.1007/s40120-022-00339-7.Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017;4(4):e360. https://doi.org/10.1212/NXI.0000000000000360.Baker D, Herrod SS, Alvarez-Gonzalez C, Zalewski L, Albor C, Schmierer K. Both cladribine and alemtuzumab may effect MS via B-cell depletion. Neurol Neuroimmunol Neuroinflamm. 2017;4(4):e360. https://doi.org/10.1212/NXI.0000000000000360.Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sørensen P et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416–426. https://doi.org/10.1056/NEJMoa0902533.Giovannoni G, Comi G, Cook S, Rammohan K, Rieckmann P, Soelberg Sørensen P et al. A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):416–426. https://doi.org/10.1056/NEJMoa0902533.Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler. 2018;24(12):1594–1604. https://doi.org/10.1177/1352458517727603.Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan K, Rieckmann P, Comi G et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler. 2018;24(12):1594–1604. https://doi.org/10.1177/1352458517727603.Pakpoor J, Disanto G, Altmann DR, Pavitt S, Turner BP, Marta M et al. No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e158. https://doi.org/10.1212/NXI.0000000000000158.Pakpoor J, Disanto G, Altmann DR, Pavitt S, Turner BP, Marta M et al. No evidence for higher risk of cancer in patients with multiple sclerosis taking cladribine. Neurol Neuroimmunol Neuroinflamm. 2015;2(6):e158. https://doi.org/10.1212/NXI.0000000000000158.Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014;13(3):257–267. https://doi.org/10.1016/S1474-4422(14)70005-5.Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP et al. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014;13(3):257–267. https://doi.org/10.1016/S1474-4422(14)70005-5.de Stefano N, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A et al. Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS. Neurol Neuroimmunol Neuroinflamm. 2022;9(4):e1187. doi: https://doi.org/10.1212/NXI.0000000000001187.de Stefano N, Barkhof F, Montalban X, Achiron A, Derfuss T, Chan A et al. Early Reduction of MRI Activity During 6 Months of Treatment With Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS. Neurol Neuroimmunol Neuroinflamm. 2022;9(4):e1187. doi: https://doi.org/10.1212/NXI.0000000000001187.Brochet B, Solari A, Lechner-Scott J, Piehl F, Langdon D, Hupperts R et al. Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study. Mult Scler. 2023;29(14):1808–1818. https://doi.org/10.1177/13524585231205962.Brochet B, Solari A, Lechner-Scott J, Piehl F, Langdon D, Hupperts R et al. Improvements in quality of life over 2 years with cladribine tablets in people with relapsing multiple sclerosis: The CLARIFY-MS study. Mult Scler. 2023;29(14):1808–1818. https://doi.org/10.1177/13524585231205962.Giovannoni G, Boyko A, Correale J, Edan G, Freedman MS, Montalban XR et al. Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension cohort of CLASSIC-MS: An ambispective study. Mult Scler. 2023;29(6):719–730. https://doi.org/10.1177/13524585231161494.Giovannoni G, Boyko A, Correale J, Edan G, Freedman MS, Montalban XR et al. Long-term follow-up of patients with relapsing multiple sclerosis from the CLARITY/CLARITY Extension cohort of CLASSIC-MS: An ambispective study. Mult Scler. 2023;29(6):719–730. https://doi.org/10.1177/13524585231161494.Leist T, Cook S, Comi G, Montalban X, Giovannoni G, Nolting A et al. Longterm safety data from the cladribine tablets clinical development program in multiple sclerosis. Mult Scler Relat Disord. 2020;46:102572. https://doi.org/10.1016/j.msard.2020.102572.Leist T, Cook S, Comi G, Montalban X, Giovannoni G, Nolting A et al. Longterm safety data from the cladribine tablets clinical development program in multiple sclerosis. Mult Scler Relat Disord. 2020;46:102572. https://doi.org/10.1016/j.msard.2020.102572.Brownlee W, Amin A, Ashton L, Herbert A. Real-world use of cladribine tablets (completion rates and treatment persistence) in patients with multiple sclerosis in England: The CLARENCE study. Mult Scler Relat Disord. 2023;79:104951. https://doi.org/10.1016/j.msard.2023.104951.Brownlee W, Amin A, Ashton L, Herbert A. Real-world use of cladribine tablets (completion rates and treatment persistence) in patients with multiple sclerosis in England: The CLARENCE study. Mult Scler Relat Disord. 2023;79:104951. https://doi.org/10.1016/j.msard.2023.104951.Spelman T, Ozakbas S, Alroughani R, Terzi M, Hodgkinson S, Laureys G et al. Comparative effectiveness of cladribine tablets versus other oral diseasemodifying treatments for multiple sclerosis: Results from MSBase registry. Mult Scler. 2023;29(2):221–235. https://doi.org/10.1177/13524585221137502.Spelman T, Ozakbas S, Alroughani R, Terzi M, Hodgkinson S, Laureys G et al. Comparative effectiveness of cladribine tablets versus other oral diseasemodifying treatments for multiple sclerosis: Results from MSBase registry. Mult Scler. 2023;29(2):221–235. https://doi.org/10.1177/13524585221137502.Leist T, Yamout B, Alexandri N, Chudecka A, Galazka A, Nolting A. Poster P416. Safety of Cladribine Tablets in the Treatment of People with Multiple Sclerosis: 2025 Post-Approval Safety Update. In: ACTRIMS Forum 2026, 5–7 Feb. San Diego, Californiа. 2026. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/actrims-2026/r-poster-actrims-2026-leist-new.pdf.Leist T, Yamout B, Alexandri N, Chudecka A, Galazka A, Nolting A. Poster P416. Safety of Cladribine Tablets in the Treatment of People with Multiple Sclerosis: 2025 Post-Approval Safety Update. In: ACTRIMS Forum 2026, 5–7 Feb. San Diego, Californiа. 2026. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/actrims-2026/r-poster-actrims-2026-leist-new.pdf.He A, Merkel B, Brown JWL, Zhovits Ryerson L, Kister I, Malpas CB et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020;19(4):307–316. https://doi.org/10.1016/S1474-4422(20)30067-3.He A, Merkel B, Brown JWL, Zhovits Ryerson L, Kister I, Malpas CB et al. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020;19(4):307–316. https://doi.org/10.1016/S1474-4422(20)30067-3.De Stefano N, Vermersch P, Wiendl H, Barkhof F, Montalban X, Achiron A et al. Poster P349. Long-Term Effectiveness of Cladribine Tablets Over 4 Years in Relapsing Multiple Sclerosis: Results From the MAGNIFY-MS Extension Study. In: ECTRIMS 2024. Copenhagen, Denmark. Available at: https://medical.emdserono.com/content/dam/web/health-care/biopharma/web/USMI/congress-presentations/neurology/ectrims-2024/p349magnify-ms-ext.pdf.De Stefano N, Vermersch P, Wiendl H, Barkhof F, Montalban X, Achiron A et al. Poster P349. Long-Term Effectiveness of Cladribine Tablets Over 4 Years in Relapsing Multiple Sclerosis: Results From the MAGNIFY-MS Extension Study. In: ECTRIMS 2024. Copenhagen, Denmark. Available at: https://medical.emdserono.com/content/dam/web/health-care/biopharma/web/USMI/congress-presentations/neurology/ectrims-2024/p349magnify-ms-ext.pdf.De Stefano N, Achiron A, Barkhof F, Chan A, Derfuss T, Hodgkinson S et al. Effect of Cladribine Tablets on Markers of Disease Progression, Axonal Loss and Oligoclonal Bands in Patients with Relapsing Multiple Sclerosis: Results from MAGNIFY-MS. Oral presentation DMT01. In: The Consortium of Multiple Sclerosis Centers (CMSC). 2024. Nashville, TN. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/CMSC_2024_De_Stefano_MAGNIFY.pdf.De Stefano N, Achiron A, Barkhof F, Chan A, Derfuss T, Hodgkinson S et al. Effect of Cladribine Tablets on Markers of Disease Progression, Axonal Loss and Oligoclonal Bands in Patients with Relapsing Multiple Sclerosis: Results from MAGNIFY-MS. Oral presentation DMT01. In: The Consortium of Multiple Sclerosis Centers (CMSC). 2024. Nashville, TN. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/CMSC_2024_De_Stefano_MAGNIFY.pdf.De Stefano N, Wiendl H, Barkhof F, Achiron A, Derfuss T, Chan A et al. Poster P326. Low Rate of Progression Independent of Relapse Activity (PIRA) in Patients With Relapsing Multiple Sclerosis Treated With Cladribine Tablets. In: ECTRIMS 2024. Copenhagen, Denmark. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/ectrims-2024/p326magnify-ms-pira.pdf.De Stefano N, Wiendl H, Barkhof F, Achiron A, Derfuss T, Chan A et al. Poster P326. Low Rate of Progression Independent of Relapse Activity (PIRA) in Patients With Relapsing Multiple Sclerosis Treated With Cladribine Tablets. In: ECTRIMS 2024. Copenhagen, Denmark. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/ectrims-2024/p326magnify-ms-pira.pdf.Rauma I, Viitala M, Kuusisto H, Atula S, Sipilä JOT, Ryytty M et al. Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study. Mult Scler Relat Disord. 2022;61:103755. https://doi.org/10.1016/j.msard.2022.103755.Rauma I, Viitala M, Kuusisto H, Atula S, Sipilä JOT, Ryytty M et al. Finnish multiple sclerosis patients treated with cladribine tablets: a nationwide registry study. Mult Scler Relat Disord. 2022;61:103755. https://doi.org/10.1016/j.msard.2022.103755.Manni A, Oggiano F, Palazzo C, Panetta V, Gargano CD, Mangialardi V et al. Clinical and biological predictors of Cladribine effectiveness in Multiple Sclerosis: A real-world, single Centre study considering a two-year interval from year-2 dosing. J Neurol Sci. 2024;462:123070. https://doi.org/10.1016/j.jns.2024.123070.Manni A, Oggiano F, Palazzo C, Panetta V, Gargano CD, Mangialardi V et al. Clinical and biological predictors of Cladribine effectiveness in Multiple Sclerosis: A real-world, single Centre study considering a two-year interval from year-2 dosing. J Neurol Sci. 2024;462:123070. https://doi.org/10.1016/j.jns.2024.123070.Zanetta C, Rocca MA, Meani A, Martinelli V, Ferrè L, Moiola L, Filippi M. Effectiveness and safety profile of cladribine in an Italian real-life cohort of relapsing-remitting multiple sclerosis patients: a monocentric longitudinal observational study. J Neurol. 2023;270(7):3553–3564. https://doi.org/10.1007/s00415-023-11700-7.Zanetta C, Rocca MA, Meani A, Martinelli V, Ferrè L, Moiola L, Filippi M. Effectiveness and safety profile of cladribine in an Italian real-life cohort of relapsing-remitting multiple sclerosis patients: a monocentric longitudinal observational study. J Neurol. 2023;270(7):3553–3564. https://doi.org/10.1007/s00415-023-11700-7.Попова ЕВ, Сосина ВБ, Шаранова СН, Золотова СН, Шалабанова ИМ, Хачанова НВ и др. Кладрибин в таблетках в реальной клинической практике: результаты лечения 267 пациентов с рассеянным склерозом в Москве. Медицинский совет. 2025;19(12):120–127. https://doi.org/10.21518/ms2025-280.Popova EV, Sosina VB, Sharanova SN, Zolotova SN, Shalabanova IM, Khachanova NV et al. Cladribine in tablets in real clinical practice: Results of treatment of 267 patients with multiple sclerosis in Moscow. Meditsinskiy Sovet. 2025;(12):120–127. (In Russ.) https://doi.org/10.21518/ms2025-280.Montalban X, Leist TP, Cohen BA, Moses H, Campbell J, Hicking C, Dangond F. Cladribine tablets added to IFN-β in active relapsing MS: The ONWARD study. Neurol Neuroimmunol Neuroinflamm. 2018;5(5):e477. https://doi.org/10.1212/NXI.0000000000000477.Montalban X, Leist TP, Cohen BA, Moses H, Campbell J, Hicking C, Dangond F. Cladribine tablets added to IFN-β in active relapsing MS: The ONWARD study. Neurol Neuroimmunol Neuroinflamm. 2018;5(5):e477. https://doi.org/10.1212/NXI.0000000000000477.Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan KW, Rieckmann P, Comi G et al. Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study. Mult Scler. 2019;25(6):819–827. https://doi.org/10.1177/1352458518771875.Giovannoni G, Soelberg Sorensen P, Cook S, Rammohan KW, Rieckmann P, Comi G et al. Efficacy of Cladribine Tablets in high disease activity subgroups of patients with relapsing multiple sclerosis: A post hoc analysis of the CLARITY study. Mult Scler. 2019;25(6):819–827. https://doi.org/10.1177/1352458518771875.von Büdingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012;122(12):4533–4543. https://doi.org/10.1172/JCI63842.von Büdingen HC, Kuo TC, Sirota M, van Belle CJ, Apeltsin L, Glanville J et al. B cell exchange across the blood-brain barrier in multiple sclerosis. J Clin Invest. 2012;122(12):4533–4543. https://doi.org/10.1172/JCI63842.Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet. 1997;32(2):120–131. https://doi.org/10.2165/00003088-199732020-00003.Liliemark J. The clinical pharmacokinetics of cladribine. Clin Pharmacokinet. 1997;32(2):120–131. https://doi.org/10.2165/00003088-199732020-00003.Hermann R, Karlsson MO, Novakovic AM, Terranova N, Fluck M, Munafo A. The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis. Clin Pharmacokinet. 2019;58(3):283–297. https://doi.org/10.1007/s40262-018-0695-9.Hermann R, Karlsson MO, Novakovic AM, Terranova N, Fluck M, Munafo A. The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis. Clin Pharmacokinet. 2019;58(3):283–297. https://doi.org/10.1007/s40262-018-0695-9.Ruggieri M, Gargano CD, Ferretta A, Manni A, Capacchione A, Frigeri A et al. Effect of Cladribine on Neuronal Apoptosis: New Insight of In Vitro Study in Multiple Sclerosis Therapy. Brain Sci. 2020;10(8):548. https://doi.org/10.3390/brainsci10080548.Ruggieri M, Gargano CD, Ferretta A, Manni A, Capacchione A, Frigeri A et al. Effect of Cladribine on Neuronal Apoptosis: New Insight of In Vitro Study in Multiple Sclerosis Therapy. Brain Sci. 2020;10(8):548. https://doi.org/10.3390/brainsci10080548.Бойко АН, Алифирова ВМ, Пашковская ДВ, Кучина ЕИ, Сиверцева СА, Турова ЕЛ и др. Опыт применения кладрибина в таблетках в реальной клинической практике: независимый анализ данных 12 российских клиник. Неврология, нейропсихиатрия, психосоматика. 2024;(16):44–50. https://doi.org/10.14412/2074-2711-2024-2S-44-50.Boyko AN, Alifirova VM, Pashkovskaya DV, Kuchina EI, Sivertseva SA, Turova EL et al. Experience with the use of cladribine tablets in real-life clinical practice: independent analysis of data from 12 Russian clinical centres. Neurology, Neuropsychiatry, Psychosomatics. 2024;(16):44–50. (In Russ.) https://doi.org/10.14412/2074-2711-2024-2S-44-50.Oreja-Guevara C, Brownlee W, Celius EG, Centonze D, Giovannoni G, Hodgkinson S et al. Expert opinion on the long-term use of cladribine tablets for multiple sclerosis: Systematic literature review of real-world evidence. Mult Scler Relat Disord. 2023;69:104459. https://doi.org/10.1016/j.msard.2022.104459.Oreja-Guevara C, Brownlee W, Celius EG, Centonze D, Giovannoni G, Hodgkinson S et al. Expert opinion on the long-term use of cladribine tablets for multiple sclerosis: Systematic literature review of real-world evidence. Mult Scler Relat Disord. 2023;69:104459. https://doi.org/10.1016/j.msard.2022.104459.Giovannoni G, Leist T, Aydemir A, Verdun Di Cantogno E. CLASSIC-MS: longterm efficacy and real-world treatment patterns for patients receiving cladribine tablets-interim data with 8–14 years follow-up. In: MSVirtual 2020: 8th Joint ACTRIMS-ECTRIMS Meeting Washington DC 25–26 September, 2020. Available at: https://www.merckneurology.com/content/dam/web/healthcare/biopharma/neurology/merckneurology/global/newsroom/abstract/CLASSIC-MS%20Long-term%20Efficacy%20and%20Real-World%20Treatment%20Patterns%20for%20Patients%20Receiving%20Cla.pdf.Giovannoni G, Leist T, Aydemir A, Verdun Di Cantogno E. CLASSIC-MS: longterm efficacy and real-world treatment patterns for patients receiving cladribine tablets-interim data with 8–14 years follow-up. In: MSVirtual 2020: 8th Joint ACTRIMS-ECTRIMS Meeting Washington DC 25–26 September, 2020. Available at: https://www.merckneurology.com/content/dam/web/healthcare/biopharma/neurology/merckneurology/global/newsroom/abstract/CLASSIC-MS%20Long-term%20Efficacy%20and%20Real-World%20Treatment%20Patterns%20for%20Patients%20Receiving%20Cla.pdf.Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS). Ther Adv Neurol Disord. 2020;13:1756286420922685. https://doi.org/10.1177/1756286420922685.Patti F, Visconti A, Capacchione A, Roy S, Trojano M; CLARINET-MS Study Group. Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS). Ther Adv Neurol Disord. 2020;13:1756286420922685. https://doi.org/10.1177/1756286420922685.Petrou P, Achiron A, Cohen EG, Garty M, Magalashvili D, Karmon Y et al. Practical recommendations on treatment of multiple sclerosis with Cladribine: an Israeli Experts Group Viewpoint. J Neurol. 2023;270(11):5188–5195. https://doi.org/10.1007/s00415-023-11846-4.Petrou P, Achiron A, Cohen EG, Garty M, Magalashvili D, Karmon Y et al. Practical recommendations on treatment of multiple sclerosis with Cladribine: an Israeli Experts Group Viewpoint. J Neurol. 2023;270(11):5188–5195. https://doi.org/10.1007/s00415-023-11846-4.Meca-Lallana V, García Domínguez JM, López Ruiz R, Martín-Martínez J, Arés Luque A, Hernández Pérez MA et al. Expert-Agreed Practical Recommendations on the Use of Cladribine. Neurol Ther. 2022;11(4):1475–1488. https://doi.org/10.1007/s40120-022-00394-0.Meca-Lallana V, García Domínguez JM, López Ruiz R, Martín-Martínez J, Arés Luque A, Hernández Pérez MA et al. Expert-Agreed Practical Recommendations on the Use of Cladribine. Neurol Ther. 2022;11(4):1475–1488. https://doi.org/10.1007/s40120-022-00394-0.Centonze D, Amato MP, Brescia Morra V, Cocco E, De Stefano N, Gasperini C et al. Multiple sclerosis patients treated with cladribine tablets: expert opinion on practical management after year 4. Ther Adv Neurol Disord. 2023;16:17562864231183221. https://doi.org/10.1177/17562864231183221.Centonze D, Amato MP, Brescia Morra V, Cocco E, De Stefano N, Gasperini C et al. Multiple sclerosis patients treated with cladribine tablets: expert opinion on practical management after year 4. Ther Adv Neurol Disord. 2023;16:17562864231183221. https://doi.org/10.1177/17562864231183221.Habek M, Drulovic J, Brecl Jakob G, Barbov I, Radulovic L, Rajda C et al. Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers. Neurol Ther. 2023;12(1):25–37. https://doi.org/10.1007/s40120-022-00422-z.Habek M, Drulovic J, Brecl Jakob G, Barbov I, Radulovic L, Rajda C et al. Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers. Neurol Ther. 2023;12(1):25–37. https://doi.org/10.1007/s40120-022-00422-z.Ciron J, Bourre B, Castelnovo G, Guennoc AM, De Sèze J, Ben-Amor AF et al. Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France. Neurol Ther. 2024;13(3):503–518. https://doi.org/10.1007/s40120-024-00589-7.Ciron J, Bourre B, Castelnovo G, Guennoc AM, De Sèze J, Ben-Amor AF et al. Holistic, Long-Term Management of People with Relapsing Multiple Sclerosis with Cladribine Tablets: Expert Opinion from France. Neurol Ther. 2024;13(3):503–518. https://doi.org/10.1007/s40120-024-00589-7.Meuth SG, Bayas A, Kallmann B, Linker R, Rieckmann P, Wattjes MP et al. Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4. Expert Opin Pharmacother. 2022;23(13):1503–1510. https://doi.org/10.1080/14656566.2022.2106783.Meuth SG, Bayas A, Kallmann B, Linker R, Rieckmann P, Wattjes MP et al. Long-term management of multiple sclerosis patients treated with cladribine tablets beyond year 4. Expert Opin Pharmacother. 2022;23(13):1503–1510. https://doi.org/10.1080/14656566.2022.2106783.Meuth SG, Bayas A, Kallmann B, Kleinschnitz C, Linker R, Rieckmann P, Mäurer M. Long-term management of multiple sclerosis patients treated with cladribine tablets: an expert opinion. Expert Opin Pharmacother. 2020;21(16):1965–1969. https://doi.org/10.1080/14656566.2020.1792885.Meuth SG, Bayas A, Kallmann B, Kleinschnitz C, Linker R, Rieckmann P, Mäurer M. Long-term management of multiple sclerosis patients treated with cladribine tablets: an expert opinion. Expert Opin Pharmacother. 2020;21(16):1965–1969. https://doi.org/10.1080/14656566.2020.1792885.Sørensen PS, Centonze D, Giovannoni G, Montalban X, Selchen D, Vermersch P et al. Expert opinion on the use of cladribine tablets in clinical practice. Ther Adv Neurol Disord. 2020;13:1756286420935019. https://doi.org/10.1177/1756286420935019.Sørensen PS, Centonze D, Giovannoni G, Montalban X, Selchen D, Vermersch P et al. Expert opinion on the use of cladribine tablets in clinical practice. Ther Adv Neurol Disord. 2020;13:1756286420935019. https://doi.org/10.1177/1756286420935019.Kowarik MC, Ernst M, Woitschach L, Cepek L, Rau D, Kühnler B et al. Realworld therapy management of patients with multiple sclerosis receiving cladribine tablets beyond year 4 – Results from a German cladribine cohort. Mult Scler Relat Disord. 2024;88:105704. http://doi:10.1016/j.msard.2024.105704.Kowarik MC, Ernst M, Woitschach L, Cepek L, Rau D, Kühnler B et al. Realworld therapy management of patients with multiple sclerosis receiving cladribine tablets beyond year 4 – Results from a German cladribine cohort. Mult Scler Relat Disord. 2024;88:105704. http://doi:10.1016/j.msard.2024.105704.Wiendl H, Gold R, Pul R, Ernst M, Kowarik MC, Klehmet J et al. Treatmentfree remission in MS: long-term disease control with cladribine tablets. J Neurol. 2026;273(4):218. https://doi.org/10.1007/s00415-026-13753-w.Wiendl H, Gold R, Pul R, Ernst M, Kowarik MC, Klehmet J et al. Treatmentfree remission in MS: long-term disease control with cladribine tablets. J Neurol. 2026;273(4):218. https://doi.org/10.1007/s00415-026-13753-w.Kleinschnitz C, Skripuletz T, Pfeuffer S, Pawlitzki M, Rieckmann P, Penner IK et al. Is therapy-free remission a realistic goal with cladribine tablets in multiple sclerosis? New insights into the mechanism of action and clinical implications of immune reconstitution with cladribine tablets in MS therapy. J Neurol. 2025;272(12):788. https://doi.org/10.1007/s00415-025-13530-1.Kleinschnitz C, Skripuletz T, Pfeuffer S, Pawlitzki M, Rieckmann P, Penner IK et al. Is therapy-free remission a realistic goal with cladribine tablets in multiple sclerosis? New insights into the mechanism of action and clinical implications of immune reconstitution with cladribine tablets in MS therapy. J Neurol. 2025;272(12):788. https://doi.org/10.1007/s00415-025-13530-1.Alvarez E, Longbrake EE, Rammohan KW, Stankiewicz J, Hersh CM. Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management. Mult Scler Relat Disord. 2023;79:105009. https://doi.org/10.1016/j.msard.2023.105009.Alvarez E, Longbrake EE, Rammohan KW, Stankiewicz J, Hersh CM. Secondary hypogammaglobulinemia in patients with multiple sclerosis on anti-CD20 therapy: Pathogenesis, risk of infection, and disease management. Mult Scler Relat Disord. 2023;79:105009. https://doi.org/10.1016/j.msard.2023.105009.Mears V, Jakubecz C, Seeco C, Woodson S, Serra A, Abboud H. Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD. J Neuroimmunol. 2023;377:578066. https://doi.org/10.1016/j.jneuroim.2023.578066.Mears V, Jakubecz C, Seeco C, Woodson S, Serra A, Abboud H. Predictors of hypogammaglobulinemia and serious infections among patients receiving ocrelizumab or rituximab for treatment of MS and NMOSD. J Neuroimmunol. 2023;377:578066. https://doi.org/10.1016/j.jneuroim.2023.578066.Oksbjerg NR, Nielsen SD, Blinkenberg M, Magyari M, Sellebjerg F. AntiCD20 antibody therapy and risk of infection in patients with demyelinating diseases. Mult Scler Relat Disord. 2021;52:102988. https://doi.org/10.1016/j.msard.2021.102988.Oksbjerg NR, Nielsen SD, Blinkenberg M, Magyari M, Sellebjerg F. AntiCD20 antibody therapy and risk of infection in patients with demyelinating diseases. Mult Scler Relat Disord. 2021;52:102988. https://doi.org/10.1016/j.msard.2021.102988.Perriguey M, Maarouf A, Stellmann JP, Rico A, Boutiere C, Demortiere S et al. Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab. Neurol Neuroimmunol Neuroinflamm. 2021;9(1):e1115. https://doi.org/10.1212/NXI.0000000000001115.Perriguey M, Maarouf A, Stellmann JP, Rico A, Boutiere C, Demortiere S et al. Hypogammaglobulinemia and Infections in Patients With Multiple Sclerosis Treated With Rituximab. Neurol Neuroimmunol Neuroinflamm. 2021;9(1):e1115. https://doi.org/10.1212/NXI.0000000000001115.Peters J, Longbrake EE. Infection risk in a real-world cohort of patients treated with long-term B-cell depletion for autoimmune neurologic disease. Mult Scler Relat Disord. 2022;68:104400. https://doi.org/10.1016/j.msard.2022.104400.Peters J, Longbrake EE. Infection risk in a real-world cohort of patients treated with long-term B-cell depletion for autoimmune neurologic disease. Mult Scler Relat Disord. 2022;68:104400. https://doi.org/10.1016/j.msard.2022.104400.Sangha KS, Jakubecz C, Maynard M, Hernandez RS, Esmaeili S, Zabeti A et al. Real world predictors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab or ofatumumab for the treatment of multiple sclerosis: The REPLACE-MS study. Mult Scler. 2026;32(3):338–346. https://doi.org/10.1177/13524585251412125.Sangha KS, Jakubecz C, Maynard M, Hernandez RS, Esmaeili S, Zabeti A et al. Real world predictors of hypogammaglobulinemia and serious infections in patients receiving ocrelizumab or ofatumumab for the treatment of multiple sclerosis: The REPLACE-MS study. Mult Scler. 2026;32(3):338–346. https://doi.org/10.1177/13524585251412125.Khatri B, Van Zealand P, Tarima S, Schutten S, Baker A, Perea T. Hypogammaglobulinemia and infection rates in patients with multiple sclerosis treated with ocrelizumab for up to six years: A real-world singlecenter study. Mult Scler J Exp Transl Clin. 2025;11(4):20552173251391975. https://doi.org/10.1177/20552173251391975.Khatri B, Van Zealand P, Tarima S, Schutten S, Baker A, Perea T. Hypogammaglobulinemia and infection rates in patients with multiple sclerosis treated with ocrelizumab for up to six years: A real-world singlecenter study. Mult Scler J Exp Transl Clin. 2025;11(4):20552173251391975. https://doi.org/10.1177/20552173251391975.Lycett MJ, Lea RA, Maltby VE, Min M, Lechner-Scott J. The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis. Mult Scler J Exp Transl Clin. 2023;9(1):20552173221149688. https://doi.org/10.1177/20552173221149688.Lycett MJ, Lea RA, Maltby VE, Min M, Lechner-Scott J. The effect of cladribine on immunoglobulin levels compared to B cell targeting therapies in multiple sclerosis. Mult Scler J Exp Transl Clin. 2023;9(1):20552173221149688. https://doi.org/10.1177/20552173221149688.Okuda D, Livingston T, Moog T, Smith A, Lebson L, Piette E. P491. RealWorld Outcomes of People with Relapsing Multiple Sclerosis Switching From Natalizumab or Ocrelizumab to Cladribine Tablets. Abstract. In: ACTRIMS 2024 Meeting, West Palm Beach, FL, USA. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/R_Poster-ACTRIMS-2024P491-Okuda-et-al-Real-World-Outcomes-Switching-to-Cladribine-Tablets_ 29-Feb-2024.pdf.Okuda D, Livingston T, Moog T, Smith A, Lebson L, Piette E. P491. RealWorld Outcomes of People with Relapsing Multiple Sclerosis Switching From Natalizumab or Ocrelizumab to Cladribine Tablets. Abstract. In: ACTRIMS 2024 Meeting, West Palm Beach, FL, USA. Available at: https://medical.emdserono.com/content/dam/web/healthcare/biopharma/web/USMI/congress-presentations/neurology/R_Poster-ACTRIMS-2024P491-Okuda-et-al-Real-World-Outcomes-Switching-to-Cladribine-Tablets_ 29-Feb-2024.pdf.Macaron G, Larochelle C, Arbour N, Galmard M, Girard JM, Prat A, Duquette P. Impact of aging on treatment considerations for multiple sclerosis patients. Front Neurol. 2023;14:1197212. https://doi.org/10.3389/fneur.2023.1197212.Macaron G, Larochelle C, Arbour N, Galmard M, Girard JM, Prat A, Duquette P. Impact of aging on treatment considerations for multiple sclerosis patients. Front Neurol. 2023;14:1197212. https://doi.org/10.3389/fneur.2023.1197212.de Seze J, Dive D, Ayrignac X, Castelnovo G, Payet M, Rayah A et al. Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis. Neurol Ther. 2024;13(3):519–533. https://doi.org/10.1007/s40120-024-00603-y.de Seze J, Dive D, Ayrignac X, Castelnovo G, Payet M, Rayah A et al. Narrative Review on the Use of Cladribine Tablets as Exit Therapy for Stable Elderly Patients with Multiple Sclerosis. Neurol Ther. 2024;13(3):519–533. https://doi.org/10.1007/s40120-024-00603-y.Zeydan B, Kantarci OH. Impact of Age on Multiple Sclerosis Disease Activity and Progression. Curr Neurol Neurosci Rep. 2020;20(7):24. https://doi.org/10.1007/s11910-020-01046-2.Zeydan B, Kantarci OH. Impact of Age on Multiple Sclerosis Disease Activity and Progression. Curr Neurol Neurosci Rep. 2020;20(7):24. https://doi.org/10.1007/s11910-020-01046-2.Tremlett H, Zhao Y, Joseph J, Devonshire V; UBCMS Clinic Neurologists. Relapses in multiple sclerosis are ageand time-dependent. J Neurol Neurosurg Psychiatry. 2008;79(12):1368–1374. https://doi.org/10.1136/jnnp.2008.145805.Tremlett H, Zhao Y, Joseph J, Devonshire V; UBCMS Clinic Neurologists. Relapses in multiple sclerosis are ageand time-dependent. J Neurol Neurosurg Psychiatry. 2008;79(12):1368–1374. https://doi.org/10.1136/jnnp.2008.145805.Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014;14(1):24–35. https://doi.org/10.1038/nri3567.Farber DL, Yudanin NA, Restifo NP. Human memory T cells: generation, compartmentalization and homeostasis. Nat Rev Immunol. 2014;14(1):24–35. https://doi.org/10.1038/nri3567.Christensen KL, Holman RC, Steiner CA, Sejvar JJ, Stoll BJ, Schonberger LB. Infectious disease hospitalizations in the United States. Clin Infect Dis. 2009;49(7):1025–1035. https://doi.org/10.1086/605562.Christensen KL, Holman RC, Steiner CA, Sejvar JJ, Stoll BJ, Schonberger LB. Infectious disease hospitalizations in the United States. Clin Infect Dis. 2009;49(7):1025–1035. https://doi.org/10.1086/605562.Castelo-Branco A, Chiesa F, Conte S, Bengtsson C, Lee S, Minton N et al. Infections in patients with multiple sclerosis: A national cohort study in Sweden. Mult Scler Relat Disord. 2020;45:102420. https://doi.org/10.1016/j.msard.2020.102420.Castelo-Branco A, Chiesa F, Conte S, Bengtsson C, Lee S, Minton N et al. Infections in patients with multiple sclerosis: A national cohort study in Sweden. Mult Scler Relat Disord. 2020;45:102420. https://doi.org/10.1016/j.msard.2020.102420.Brand JS, Smith KA, Piehl F, Olsson T, Montgomery S. Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study. Brain Behav Immun Health. 2022;22:100470. https://doi.org/10.1016/j.bbih.2022.100470.Brand JS, Smith KA, Piehl F, Olsson T, Montgomery S. Risk of serious infections in multiple sclerosis patients by disease course and disability status: Results from a Swedish register-based study. Brain Behav Immun Health. 2022;22:100470. https://doi.org/10.1016/j.bbih.2022.100470.Rammohan K, Giovannoni G, Comi G, Cook S, Rieckmann P, Soelberg Sørensen P et al. Cladribine tablets for relapsing-remitting multiple sclerosis: Efficacy across patient subgroups from the phase III CLARITY study. Mult Scler Relat Disord. 2012;1(1):49–54. https://doi.org/10.1016/j.msard.2011.08.006.Rammohan K, Giovannoni G, Comi G, Cook S, Rieckmann P, Soelberg Sørensen P et al. Cladribine tablets for relapsing-remitting multiple sclerosis: Efficacy across patient subgroups from the phase III CLARITY study. Mult Scler Relat Disord. 2012;1(1):49–54. https://doi.org/10.1016/j.msard.2011.08.006.Giovannoni G, Rammohanb K, Cookc S, Soelberg-Sorensend P, Vermersche P, Kellerf B, Verdun di Cantogno E. Efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing multiple sclerosis aged above and below 45 years; clarity and clarity extension. J Neurol Sci. 2019;405:177–178. https://doi.org/10.1016/j.jns.2019.10.1122.Giovannoni G, Rammohanb K, Cookc S, Soelberg-Sorensend P, Vermersche P, Kellerf B, Verdun di Cantogno E. Efficacy of cladribine tablets 3.5 mg/kg in patients with relapsing multiple sclerosis aged above and below 45 years; clarity and clarity extension. J Neurol Sci. 2019;405:177–178. https://doi.org/10.1016/j.jns.2019.10.1122.Disanto G, Moccia M, Sacco R, Spiezia AL, Carotenuto A, Brescia Morra V et al. Monitoring of safety and effectiveness of cladribine in multiple sclerosis patients over 50 years. Mult Scler Relat Disord. 2022;58:103490. https://doi.org/10.1016/j.msard.2022.103490.Disanto G, Moccia M, Sacco R, Spiezia AL, Carotenuto A, Brescia Morra V et al. Monitoring of safety and effectiveness of cladribine in multiple sclerosis patients over 50 years. Mult Scler Relat Disord. 2022;58:103490. https://doi.org/10.1016/j.msard.2022.103490.Adamec I, Brecl Jakob G, Rajda C, Drulović J, Radulović L, Bašić Kes V et al. Cladribine tablets in people with relapsing multiple sclerosis: A realworld multicentric study from southeast European MS centers. J Neuroimmunol. 2023;382:578164. https://doi.org/10.1016/j.jneuroim.2023.578164.Adamec I, Brecl Jakob G, Rajda C, Drulović J, Radulović L, Bašić Kes V et al. Cladribine tablets in people with relapsing multiple sclerosis: A realworld multicentric study from southeast European MS centers. J Neuroimmunol. 2023;382:578164. https://doi.org/10.1016/j.jneuroim. 2023.578164.Sorensen PS, Pontieri L, Joensen H, Heick A, Rasmussen PV, Schäfer J et al. Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study. Mult Scler Relat Disord. 2023;70:104491. https://doi.org/10.1016/j.msard.2022.104491.Sorensen PS, Pontieri L, Joensen H, Heick A, Rasmussen PV, Schäfer J et al. Real-world experience of cladribine treatment in relapsing-remitting multiple sclerosis: A Danish nationwide study. Mult Scler Relat Disord. 2023;70:104491. https://doi.org/10.1016/j.msard.2022.104491.Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A et al. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021;12:763433. https://doi.org/10.3389/fimmu.2021.763433.Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A et al. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021;12:763433. https://doi.org/10.3389/fimmu.2021.763433.Ostolaza A, Corroza J, Ayuso T. Multiple sclerosis and aging: comorbidity and treatment challenges. Mult Scler Relat Disord. 2021;50:102815. https://doi.org/10.1016/j.msard.2021.102815.Ostolaza A, Corroza J, Ayuso T. Multiple sclerosis and aging: comorbidity and treatment challenges. Mult Scler Relat Disord. 2021;50:102815. https://doi.org/10.1016/j.msard.2021.102815.

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