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Aktuelle Neurologie 2016; 43(08): 511-518
DOI: 10.1055/s-0042-114976
Übersicht
© Georg Thieme Verlag KG Stuttgart · New York

MS-assoziierte Fatigue – Welche Immuntherapie hilft?

Impact of Disease-Modifying Therapies on Fatigue in Multiple Sclerosis
H.U. Voelter
1   Neurologische Klinik Bremen-Ost
,
H. Hildebrandt
1   Neurologische Klinik Bremen-Ost
,
A. Kastrup
1   Neurologische Klinik Bremen-Ost
› Author Affiliations
Further Information

Publication History

Publication Date:
15 September 2016 (online)

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Zusammenfassung

Hintergrund: Fatigue ist bei Patienten mit Multiple Sklerose ein häufiges Symptom mit maßgeblichem Einfluss auf die Lebensqualität der Erkrankten. Durch Immuntherapien kann der Krankheitsverlauf der Multiple Sklerose günstig beeinflusst werden, insbesondere die Schubfrequenz. Wenig untersucht ist dagegen die Wirksamkeit der verschiedenen Immuntherapien auf MS-assoziierte Fatigue.

Ziel der Arbeit: In der vorliegenden Übersicht stellen wir für alle derzeit zugelassenen Immuntherapeutika ausführlich dar, welche Daten zu deren Fatigue-Wirksamkeit vorliegen. Anschließend werden die Ergebnisse zusammengefasst, diskutiert und es werden Hinweise gegeben, wie diese Studienergebnisse in die klinische Praxis einfließen können.

Ergebnis: Nur für Teriflunomid liegen Daten aus mehreren randomisierten, kontrollierten Studien vor; die Ergebnisse sind negativ. Ein fehlender oder allenfalls marginaler Effekt auf das Fatigue-Erleben der MS-Patienten ist auch für die Gruppe der Beta-Interferone anzunehmen. Für Glatirameracetat, Fingolimod und Natalizumab liegen positive Studienresultate vor. Der Evidenzgrad ist jedoch gering und weitere Studien sind dringend erforderlich. Für alle übrigen Substanzen liegen derzeit keine ausreichenden Daten vor.

Abstract

Fatigue is one of the most common symptoms of multiple sclerosis (MS) and has a negative effect on quality of life. Therefore, the potential impact of disease-modifying drugs (DMDs) on fatigue is receiving increasing attention. This review article summarizes the current data on the potential impact of DMDs on fatigue in MS. To date, this issue has not been directly addressed by controlled studies. While interferon-beta and teriflunomide have been reported to be at best moderately effective, the use of natalizumab, glatiramer acetate or fingolimod has shown positive influence on fatigue. No data are available on the efficacy of other DMDs on fatigue. Further randomized trials are urgently needed.

Schlüsselwörter

Multiple Sklerose - Fatigue - Immuntherapie - Übersicht

Keywords

multiple sclerosis - fatigue - review - disease-modifying therapy
 

  • Literatur

  • 1 Hildebrandt H, Schwendemann G. Kognitive Beeinträchtigungen bei Multipler Sklerose. Schönle BB, Zieger A. (Hrsg.) Neurorehabilitation bei diffuser Hirnschädigung. Bad Honnef: Hippokampus Verlag; 2004
    Google Scholar
  • 2 Lerdal A, Celius EG, Moum T. Fatigue and its association with sociodemographic variables among multiple sclerosis patients. Multiple Sclerosis 2003; 9: 509-514
    CrossrefPubMedGoogle Scholar
  • 3 Kahn F, Amatya B, Galea M (2014) Management of fatigue in persons with multiple sclerosis. Front Neurol 2014; 177 DOI: 10.3389/fneur.2014.00177. eCollection
    PubMedGoogle Scholar
  • 4 Stangel M, Penner IK, Kallmann BA et al. Multiple Sclerosis Decision Model (MSDM): Entwicklung eines Mehrfaktorenmodells zur Beurteilung des Therapie- und Krankheitsverlaufs bei schubförmiger Multipler Sklerose. Akt Neurol 2013; 40: 486-493
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Hadjimichael O, Vollmer T, Oleen-Burkey M. Fatigue characteristics in multiple sclerosis: the North American Research Committee on Multiple Sclerosis (NARCOMS) survey. Health Qual Life Outcomes 2008; 6: 100 DOI: 10.1186/1477-7525-6-100.
    CrossrefPubMedGoogle Scholar
  • 6 Putzki N, Katsarava Z, Vago S et al. Prevalence and severity of multiple sclerosis-associated fatigue in treated and untreated patients. Eur Neurol 2008; 59: 136-142
    CrossrefPubMedGoogle Scholar
  • 7 Metz LM, Patten SB, Archibald CJ et al. The effect of immunomodulatory treatment on multiple sclerosis fatigue. J Neurol Neurosurg Psychiatry 2004; 75: 1045-1047
    CrossrefPubMedGoogle Scholar
  • 8 Ebers GC, Rice G, Lesaux J et al. Randomised double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet 1998; 352: 1498-1504
    CrossrefPubMedGoogle Scholar
  • 9 Melanson M, Grossberndt A, Klowak M et al. Fatigue and cognition in patients with relapsing multiple sclerosis treated with interferon beta. Int J Neurosci 2010; 120: 631-640
    CrossrefPubMedGoogle Scholar
  • 10 Simone IL, Ceccarelli A, Tortorella C et al. Influence of Interferon beta treatment on quality of life in multiple sclerosis patients. Health Qual Life Outcomes 2006; 4: 96
    CrossrefPubMedGoogle Scholar
  • 11 Patti F, Amato MP, Bastianello S et al. Subcutaneous interferon beta-1a has a positive effect on cognitive performance in mildly disabled patients with relapsing-remitting multiple sclerosis: 2-year results from the COGIMUS study. Ther Adv Neurol Dis 2009; 2: 67-77
    CrossrefPubMedGoogle Scholar
  • 12 Patti F, Amato MP, Trojano M et al. Quality of life, depression and fatigue in mildly disabled patients with relapsing-remitting multiple sclerosis receiving subcutaneous interferon beta-1a: 3-year results from the COGIMUS (COGnitive Impairment in MUltiple Sclerosis) study. Mult Scler 2011; 17: 991-1001
    CrossrefPubMedGoogle Scholar
  • 13 Jongen PJ, Lehnick D, Sanders E et al. Health-related quality of life in relapsing remitting multiple sclerosis patients during treatment with glatiramer acetate: a prospective, observational, international, multi-centre study. Health Qual Life Outcomes 2010; 8: 133
    CrossrefPubMedGoogle Scholar
  • 14 Jongen PJ, Lehnick D, Koeman J et al. Fatigue and health-related quality of life in relapsing-remitting multiple sclerosis after 2 years glatiramer acetate treatment are predicted by changes at 6 months: an observational multi-center study. J Neurol 2014; 261: 1469-1476
    CrossrefPubMedGoogle Scholar
  • 15 Ziemssen T, Hoffman J, Apfel R et al. Effects of glatiramer acetate on fatigue and days of absence from work in first-time treated relapsing-remitting multiple sclerosis. Health Qual Life Outcomes 2008; 6: 67
    CrossrefPubMedGoogle Scholar
  • 16 Ziemssen T, Bajenaru OA, Carra A et al. A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial. J Neurol 2014; 261: 2101-2111
    CrossrefPubMedGoogle Scholar
  • 17 Ziemssen T, Calabrese P, Penner IK et al. QualiCOP: an open-label, prospective, observational study of glatiramer acetate in patients with relapsing-remitting multiple sclerossis. EPoster4140. Eur J Neurol 2014; (Suppl. 01) 104-387
    PubMedGoogle Scholar
  • 18 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
  • 19 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
  • 20 Miller AE, Wolinsky JS, Kappos L et al. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol 2014; 13: 977-986
    CrossrefPubMedGoogle Scholar
  • 21 Vermersch P, Czlonkowska A, Grimaldi LME et al. Teriflunomide versus subcutaneous interferon beta-1 a in patients with relapsing multiple sclerosis: a randomised, controlled phase 3 trial. Mult Scler 2014; 20: 705-716
    CrossrefPubMedGoogle Scholar
  • 22 Cohen JA, Barkhof F, Comi G et al. Oral Fingolimod or Intramuscular Interferon for Relapsing Multiple Sclerosis. N Engl J Med 2010; 362: 402-415
    CrossrefPubMedGoogle Scholar
  • 23 Kappos L, Radue EW, O’Connor P et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362: 387-401
    CrossrefPubMedGoogle Scholar
  • 24 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
  • 25 Fox E, Edwards K, Burch G et al. Outcomes of switching directly to oral fingolimod from injectable therapies: Results of the randomized, open-label, multicenter, Evaluate Patient OutComes (EPOC) study in relapsing multiple sclerosis. Mult Scler Relat Dis 2014; 3: 607-619
    PubMedGoogle Scholar
  • 26 Calkwood J, Cree B, Crayton H et al. Impact of a switch to fingolimod versus staying on glatiramer acetate or beta interferons on patient- and physician-reported outcomes in relapsing multiple sclerosis: post hoc analyses of the EPOC trial. BMC Neurology 2014; 14: 220
    CrossrefPubMedGoogle Scholar
  • 27 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
  • 28 Svenningsson A, Falk E, Celius EG et al. Natalizumab treatment reduces fatigue in multiple sclerosis. Results from the TYNERGY Trial; a study in the real life setting. PLoS ONE 2013; 8: e58643
    CrossrefPubMedGoogle Scholar
  • 29 Penner IK, Sivertsdotter EC, Celius EG et al. Improvement in fatigue during natalizumab treatment is linked to improvement in depression and day-time sleepiness. Front Neurol 2015; 18: 1-5
    PubMedGoogle Scholar
  • 30 Wilken J, Kane RL, Sullivan CL et al. Changes in fatigue and cognition in patients with relapsing forms of multiple sclerosis treated with natalizumab. Int J MS Care 2013; 15: 120-128
    CrossrefPubMedGoogle Scholar
  • 31 Iaffaldano P, Viterbo RG, Paolicelli D et al. Impact of natalizumab on cognitive performances and fatigue in relapsing multiple sclerosis: a prospective, open-label, two years observational study. PLoS One 2012; 7: e35843
    CrossrefPubMedGoogle Scholar
  • 32 Stephenson JJ, Kern DM, Agarwal SS et al. Impact of natalizumab on patient-reported outcomes in multiple sclerosis: a longitudinal study. Health Qual Life Outcomes 2012; 10: 155
    CrossrefPubMedGoogle Scholar
  • 33 Putzki N, Yaldizli Ö, Tettenborn B et al. Multiple sclerosis associated fatigue during natalizumab treatment. J Neurol Sci 2009; 285: 109-113
    CrossrefPubMedGoogle Scholar
  • 34 Yildiz M, Tettenborn B, Borgwardt S. Trajectory of fatigue severity in natalizumab treated multiple sclerosis patients. Clin Neurol and Neurosurg 2013; 115: 902-903
    PubMedGoogle Scholar
  • 35 Yildiz M, Tettenborn B, Putzki N. Multiple sclerosis-associated fatigue during disease-modifying treatment with natalizumab, interferon-beta and glatiramer acetate. Eur Neurol 2011; 65: 231-232
    CrossrefPubMedGoogle Scholar
  • 36 Ostberg A, Pittas F, Taylor B. Use of low-dose mitozantrone to treat aggressive multiple sclerosis: a single-centre open-label study using patient self-assessment and clinical measures of multiple sclerosis status. Intern Med J 2005; 35: 382-387
    CrossrefPubMedGoogle Scholar
  • 37 Gold R, Giovannoni G, Phillips JT et al. Efficacy and safety of delayed-release dimethyl fumarate in patients newly diagnosed with relapsing-remitting multiple sclerosis (RRMS). Mult Scler 2015; 21: 57-66
    CrossrefPubMedGoogle Scholar
  • 38 Kita M, Fox RJ, Gold R et al. Effects of elayed-release Dimethyl Fumarate (DMF) on health-related quality of life in patients with relapsing-remitting multiple sclerosis: an integrated analysis of the phase 3 DEFINE and CONFIRM Studies. Clin Ther 2014; 36: 1958-1971
    CrossrefPubMedGoogle Scholar
  • 39 Moreau T, Havrdova E, Giovannoni G et al. Alemtuzumab improves quality of life in relapsing-remitting multiple sclerosis patients who relapsed on prior therapy: three-year follow-up of CARE-MS II. ECTRIMS Online Libr 2014; 63751
    PubMedGoogle Scholar