Neue Therapieansätze bei Multipler Sklerose inkl. Stellenwert älterer Präparate

 

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Kaum andere medizinische Fachrichtungen haben sie derart entwickelt wie die Neurologie – besondere Fortschritte in der Behandlung der Multiplen Sklerose (MS) sind festzuhalten. Krankheitsmodifizierende Therapien (DMT) ermöglichen eine hocheffektive Beeinflussung des Krankheitsverlaufs. Dieser Beitrag versucht einen Überblick geben, welche Immuntherapeutika zur individualisierten Behandlung von MS-Patienten zur Verfügung stehen und praktische Hinweise für deren Anwendung.

Abstract

The landscape of immunotherapies in the management of Multiple Sclerosis (MS) is currently particularly dynamic. Over 21 immunotherapeutic options are approved by the European Meidcines Agency (EMA), Food and Drug Administration (FDA) and newer approaches are ongoing in clinical trials. With advancements in the understanding of MS pathophysiology and further development of diagnosis criteria, newer and more specific disease-modifying therapies (DMTs) have emerged in recent years. The selection and timing of proper therapeutic approaches is increasingly complex. We provide an overview of the available immunotherapies for a personalized MS treatment and discuss practical insights into their application. The importance of early intervention, distinction between escalation and induction approaches, and consideration of high-efficacy treatments for specific patient groups are in discussed. We emphasize the significance of a patient-centered approach, taking into account various factors such as comorbidities, family planning, administration preferences and potential side effects in treatment decision-making.

Publication History

Article published online:
25 January 2024

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• Literatur

• 1 Li R, Tang H, Burns JC. et al. BTK inhibition limits B-cell-T-cell interaction through modulation of B-cell metabolism: implications for multiple sclerosis therapy. Acta Neuropathol 2022; 143: 505-521
  CrossrefPubMedGoogle Scholar
• 2 Tintoré M. Early MS treatment. Int MS J 2007; 14: 5-10
  PubMedGoogle Scholar
• 3 AlSharoqi IA, Aljumah M, Bohlega S. et al. Immune Reconstitution Therapy or Continuous Immunosuppression for the Management of Active Relapsing-Remitting Multiple Sclerosis Patients? A Narrative Review. Neurol Ther 2020; 9: 55-66
  CrossrefPubMedGoogle Scholar
• 4 Brown JWL, Coles A, Horakova D. et al. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis. JAMA 2019; 321: 175-187
  CrossrefPubMedGoogle Scholar
• 5 Wattjes MP, Ciccarelli O, Reich DS. et al. 2021 MAGNIMSCMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol 2021; 20: 653-670
  CrossrefPubMedGoogle Scholar
• 6 Wiendl H, Gold R, Berger T. et al. Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper). Nervenarzt 2021; 92: 773-801
  CrossrefPubMedGoogle Scholar
• 7 Hojati Z, Kay M, Dehghanian F. Chapter 15 – Mechanism of Action of Interferon Beta in Treatment of Multiple Sclerosis. In: Minagar A (eds.) Multiple Sclerosis. San Diego: Academic Press; 2016: 365-392
  Google Scholar
• 8 Kappos L. Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352: 1491-1497
  CrossrefPubMedGoogle Scholar
• 9 La Mantia L, Vacchi L, Di Pietrantonj C. et al. Interferon beta for secondary progressive multiple sclerosis. Cochrane Database Syst Rev 2012; 1: CD005181
  PubMedGoogle Scholar
• 10 Hellwig K, Geissbuehler Y, Sabidó M. et al. Pregnancy outcomes in interferon-beta-exposed patients with multiple sclerosis: results from the European Interferon-beta Pregnancy Registry. J Neurol 2020; 267: 1715-1723
  CrossrefPubMedGoogle Scholar
• 11 Schrempf W, Ziemssen T. Glatiramer acetate: mechanisms of action in multiple sclerosis. Autoimmun Rev 2007; 6: 469-475
  CrossrefPubMedGoogle Scholar
• 12 Khan O, Rieckmann P, Boyko A. et al. Three times weekly glatiramer acetate in relapsing-remitting multiple sclerosis. Ann Neurol 2013; 73: 705-713
  CrossrefPubMedGoogle Scholar
• 13 Boster A, Bartoszek MP, O'Connell C. et al. Efficacy, safety, and cost-effectiveness of glatiramer acetate in the treatment of relapsing-remitting multiple sclerosis. Ther Adv Neurol Disord 2011; 4: 319-332
  CrossrefPubMedGoogle Scholar
• 14 Wolinsky JS, Narayana PA, O`Connor P. et al. Glatiramer acetate in primary progressive multiple sclerosis: results of a multinational, multicenter, double-blind, placebo-controlled trial. Ann Neurol 2007; 61: 14-24
  CrossrefPubMedGoogle Scholar
• 15 Comi G, Martinelli V, Rodegher M. et al. Effect of glatiramer acetate on conversion to clinically definite multiple sclerosis in patients with clinically isolated syndrome (PreCISe study): a randomised, double-blind, placebo-controlled trial. Lancet 2009; 374: 1503-1511
  CrossrefPubMedGoogle Scholar
• 16 Gold R, Kappos L, Arnold DL. et al. Placebo-Controlled Phase 3 Study of Oral BG-12 for Relapsing Multiple Sclerosis. N Engl J Med 2012; 367: 1098-1107
  CrossrefPubMedGoogle Scholar
• 17 Wray S, Then Bergh F, Wundes A. et al. Efficacy and Safety Outcomes with Diroximel Fumarate After Switching from Prior Therapies or Continuing on DRF: Results from the Phase 3 EVOLVE-MS-1 Study. Adv Ther 2022; 39: 1810-1831
  CrossrefPubMedGoogle Scholar
• 18 Fox RJ, Miller DH, Phillips JT. et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367: 1087-1097
  CrossrefPubMedGoogle Scholar
• 19 Naismith RT, Wundes A, Ziemssen T. et al. Diroximel Fumarate Demonstrates an Improved Gastrointestinal Tolerability Profile Compared with Dimethyl Fumarate in Patients with Relapsing-Remitting Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III EVOLVE-MS-2 Study. CNS Drugs 2020; 34: 185-196
  CrossrefPubMedGoogle Scholar
• 20 O'Connor P, Wolinsky JS, Confavreux C. et al. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365: 1293-1303
  CrossrefPubMedGoogle Scholar
• 21 Confavreux C, O´Connor P, Comi G. et al. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13: 247-256
  CrossrefPubMedGoogle Scholar
• 22 Vermersch P, Czlonkowska A, Grimaldi LME. et al. Teriflunomide versus subcutaneous interferon beta-1a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler 2014; 20: 705-716
  CrossrefPubMedGoogle Scholar
• 23 Göttle P, Manousi A, Kremer D. et al. Teriflunomide promotes oligodendroglial differentiation and myelination. J Neuroinflammation 2018; 15: 76
  CrossrefPubMedGoogle Scholar
• 24 Malla B, Cotten S, Ulshoefer R. et al. Teriflunomide preserves peripheral nerve mitochondria from oxidative stress-mediated alterations. Ther Adv Chronic Dis 2020; 11 DOI: 10.1177/2040622320944773.
  CrossrefPubMedGoogle Scholar
• 25 Constantinescu V, Haase R, Akgün K. et al. S1P receptor modulators and the cardiovascular autonomic nervous system in multiple sclerosis: a narrative review. Ther Adv Neurol Disord 2022; 15 DOI: 10.1177/17562864221133163.
  CrossrefPubMedGoogle Scholar
• 26 Calabresi PA, Radue EW, Goodin D. et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13: 545-556
  CrossrefPubMedGoogle Scholar
• 27 Kappos L, Fox RJ, Burcklen M. et al. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol 2021; 78: 558-567
  CrossrefPubMedGoogle Scholar
• 28 Cohen JA, Comi G, Selmaj KW. et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol 2019; 18: 1021-1033
  CrossrefPubMedGoogle Scholar
• 29 Kappos L, Bar-Or A, Cree BAC. et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet 2018; 391: 1263-1273
  CrossrefPubMedGoogle Scholar
• 30 Roach CA, Cross AH. Anti-CD20 B Cell Treatment for Relapsing Multiple Sclerosis. Front Neurol 2020; 11: 595547
  CrossrefPubMedGoogle Scholar
• 31 Hauser SL, Waubant E, Arnold DL. et al. B-Cell Depletion with Rituximab in Relapsing-Remitting Multiple Sclerosis. N Engl J Med 2008; 358: 676-688
  CrossrefPubMedGoogle Scholar
• 32 Hauser SL, Bar-Or A, Comi G. et al. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med 2016; 376: 221-234
  CrossrefPubMedGoogle Scholar
• 33 Montalban X, Hauser SL, Kappos L. et al. Ocrelizumab versus Placebo in Primary Progressive Multiple Sclerosis. N Engl J Med 2016; 376: 209-220
  CrossrefPubMedGoogle Scholar
• 34 Fox EJ, Markowitz C, Applebee A. et al. Ocrelizumab reduces progression of upper extremity impairment in patients with primary progressive multiple sclerosis: Findings from the phase III randomized ORATORIO trial. Mult Scler 2018; 24: 1862-1870
  CrossrefPubMedGoogle Scholar
• 35 Comi G, Bermel R, Bar-Or A. et al. A multicentre, open label, single-arm, phase 3b study (CONSONANCE) to assess the effectiveness and safety of ocrelizumab in patients with primary and secondary progressive multiple sclerosis: year-1 interim analysis. Neurology 2022; 98: 652
  CrossrefPubMedGoogle Scholar
• 36 Hauser SL, Bar-Or A, Cohen JA. et al. Ofatumumab versus Teriflunomide in Multiple Sclerosis. N Engl J Med 2020; 383: 546-557
  CrossrefPubMedGoogle Scholar
• 37 Kümpfel T, Thiel S, Meinl I. et al. Anti-CD20 therapies and pregnancy in neuroimmunologic disorders: A cohort study from Germany. Neurol Neuroimmunol Neuroinflamm 2021; 8: e913
  CrossrefPubMedGoogle Scholar
• 38 Schwake C, Steinle J, Thiel S. et al. Effects of anti-CD20 therapies on infant health and physiological B-cell development if administered before or during pregnancy and/or lactation. ECTRIMS 2022, Abstract O036. Mult Scler J 2022; 28: 3-129
  PubMedGoogle Scholar
• 39 Selewski DT, Shah GV, Segal BM. et al. Natalizumab (Tysabri). AJNR Am J Neuroradiol 2010; 31: 1588-1590
  CrossrefPubMedGoogle Scholar
• 40 Polman CH, O'Connor PW, Havrdova E. et al. A Randomized, Placebo-Controlled Trial of Natalizumab for Relapsing Multiple Sclerosis. N Engl J Med 2006; 354: 899-910
  CrossrefPubMedGoogle Scholar
• 41 Butzkueven H, Kappos L, Wiendl H. et al. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry 2020; 91: 660-668
  CrossrefPubMedGoogle Scholar
• 42 Foley JF, Defer G, Ryerson LZ. et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): a randomised, controlled, open-label, phase 3b trial. Lancet Neurol 2022; 21: 608-619
  CrossrefPubMedGoogle Scholar
• 43 Trojano M, Ramió-Torrentà L, Grimaldi LM. et al. A randomized study of natalizumab dosing regimens for relapsingremitting multiple sclerosis. Mult Scler 2021; 27: 2240-2253
  CrossrefPubMedGoogle Scholar
• 44 Ho PR, Koendgen H, Campbell N. et al. Risk of natalizumabassociated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol 2017; 16: 925-933
  CrossrefPubMedGoogle Scholar
• 45 Friend S, Richman S, Bloomgren G. et al. Evaluation of pregnancy outcomes from the Tysabri (natalizumab) pregnancy exposure registry: a global, observational, follow-up study. BMC Neurol 2016; 16: 150
  CrossrefPubMedGoogle Scholar
• 46 Cohen JA, Coles AJ, Arnold DL. 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
  CrossrefPubMedGoogle Scholar
• 47 Havrdova E, Arnold DL, Cohen JA. et al. Alemtuzumab CAREMS I 5-year follow-up: Durable efficacy in the absence of continuous MS therapy. Neurology 2017; 89: 1107-1116
  CrossrefPubMedGoogle Scholar
• 48 Ziemssen T, Thomas K. Alemtuzumab in the long-term treatment of relapsing-remitting multiple sclerosis: an update on the clinical trial evidence and data from the real world. Ther Adv Neurol Disord 2017; 10: 343-359
  CrossrefPubMedGoogle Scholar
• 49 Havrdova E, Horakova D, Kovarova I. Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use. Ther Adv Neurol Disord 2015; 8: 31-45
  CrossrefPubMedGoogle Scholar
• 50 Saxena G, Moore JM, Jones M. et al. Detecting and predicting neutralization of alemtuzumab responses in MS. Neurol Neuroimmunol Neuroinflamm 2020; 7: e767
  CrossrefPubMedGoogle Scholar
• 51 Giovannoni G, Comi G, Cook S. et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis. N Engl J Med 2010; 362: 416-426
  CrossrefPubMedGoogle Scholar
• 52 Rice GPA, Filippi M, Comi G. Cladribine and progressive MS. Clinical and MRI outcomes of a multicenter controlled trial. Neurology 2000; 54: 1145-1155
  CrossrefPubMedGoogle Scholar
• 53 Geladaris A, Torke S, Weber MS. Bruton's Tyrosine Kinase Inhibitors in Multiple Sclerosis: Pioneering the Path Towards Treatment of Progression?. CNS Drugs 2022; 36: 1019-1030
  CrossrefPubMedGoogle Scholar
• 54 Mahad DH, Trapp BD, Lassmann H. Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 2015; 14: 183-193
  CrossrefPubMedGoogle Scholar