Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Treatment Options in Neurology
Erschienen in: Current Treatment Options in Neurology 8/2016

01.08.2016 | Multiple Sclerosis and Related Disorders (P Villoslada, Section Editor)

Use of Disease-Modifying Therapies in Pediatric MS

verfasst von: Marta Simone, MD, Tanuja Chitnis, MD

Erschienen in: Current Treatment Options in Neurology | Ausgabe 8/2016

Einloggen, um Zugang zu erhalten

Opinion statement

Pediatric multiple sclerosis (PedMS) is a rare disease with a more severe prognosis compared to adult-onset MS. It remains a challenging condition to treat because of the highly inflammatory nature of the disease, the prominent cognitive issues, and the limited knowledge about the efficacy and safety of current available disease-modifying therapies. Over the past decade, there has been a dramatic increase in the number of drugs licensed for adult-onset MS and several of them, although not tested in PedMS, are currently being used off-label in this population. To date, interferon-beta and glatiramer acetate are the most commonly used first-line treatments in children, although the efficacy and safety of these drugs have only been studied in observational cohorts and in unblinded randomized controlled trials. For children with breakthrough disease, escalation to higher efficacious second-line therapies, such as natalizumab, fingolimod, dimethyl fumarate, mitoxantrone, cyclophosphamide, rituximab, and daclizumab may be considered. Large observational studies showed natalizumab is an effective treatment with safety and efficacy comparable to those in adult populations. The safety, efficacy, and tolerability of the other second-line treatments in PedMS have been reported only in small size retrospective case series. Large phase III studies are underway which will provide important information regarding the efficacy and safety of fingolimod, teriflunomide, and dimethyl fumarate in PedMS. Symptomatic treatments for fatigue, spasticity, depression, bladder and bowel dysfunction, and neuropathic pain should be considered in PedMS, especially when these symptoms impact the quality of life. Further work is needed to ensure that new trials best address treatment outcomes tailored to PedMS.
Literatur
1.
Hanefeld F et al. Multiple sclerosis in childhood: report of 15 cases. Brain Dev. 1991;13(6):410–6.CrossRefPubMed
2.
Sindern E et al. Early onset MS under the age of 16: clinical and paraclinical features. Acta Neurol Scand. 1992;86(3):280–4.CrossRefPubMed
3.
Banwell B et al. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol. 2007;6(10):887–902.CrossRefPubMed
4.
Boiko A et al. Early onset multiple sclerosis: a longitudinal study. Neurology. 2002;59(7):1006–10.CrossRefPubMed
5.
Chitnis T et al. Demographics of pediatric-onset multiple sclerosis in an MS center population from the Northeastern United States. Mult Scler. 2009;15(5):627–31.CrossRefPubMed
6.
Duquette P et al. Multiple sclerosis in childhood: clinical profile in 125 patients. J Pediatr. 1987;111(3):359–63.CrossRefPubMed
7.
Ghezzi A et al. Multiple sclerosis in childhood: clinical features of 149 cases. Mult Scler. 1997;3(1):43–6.CrossRefPubMed
8.
Guilhoto LM et al. Pediatric multiple sclerosis report of 14 cases. Brain Dev. 1995;17(1):9–12.CrossRefPubMed
9.
Mikaeloff Y et al. Prognostic factors for early severity in a childhood multiple sclerosis cohort. Pediatrics. 2006;118(3):1133–9.CrossRefPubMed
10.•
Renoux C et al. Natural history of multiple sclerosis with childhood onset. N Engl J Med. 2007;356(25):2603–13. Largest study demonstrating slower time to EDSS landmarks in pediatric-onset MS compared to adult-onset MS, yet younger age at these disability landmarks in pediatric-onset MS patients.CrossRefPubMed
11.
Ruggieri M et al. Multiple sclerosis in children under 6 years of age. Neurology. 1999;53(3):478–84.CrossRefPubMed
12.
Selcen D, Anlar B, Renda Y. Multiple sclerosis in childhood: report of 16 cases. Eur Neurol. 1996;36(2):79–84.CrossRefPubMed
13.
Simone IL et al. Course and prognosis in early-onset MS: comparison with adult-onset forms. Neurology. 2002;59(12):1922–8.CrossRefPubMed
14.
Reinhardt K et al. Multiple sclerosis in children and adolescents: incidence and clinical picture—new insights from the nationwide German surveillance (2009–2011). Eur J Neurol. 2014;21(4):654–9.CrossRefPubMed
15.
Ruggieri M et al. Multiple sclerosis in children under 10 years of age. Neurol Sci. 2004;25 Suppl 4:S326–35.CrossRefPubMed
16.
Fromont A et al. Geographic variations of multiple sclerosis in France. Brain. 2010;133(Pt 7):1889–99.CrossRefPubMed
17.
18.
Pohl D et al. Paediatric multiple sclerosis and acute disseminated encephalomyelitis in Germany: results of a nationwide survey. Eur J Pediatr. 2007;166(5):405–12.CrossRefPubMed
19.•
Gorman MP et al. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol. 2009;66(1):54–9. First study demonstrating that children with MS have two to three times as many relapses as adult-onset MS patients.CrossRefPubMed
20.
Benson LA et al. Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord. 2014;3(2):186–93.CrossRefPubMed
21.
Yeh EA et al. Magnetic resonance imaging characteristics of children and adults with paediatric-onset multiple sclerosis. Brain. 2009;132(Pt 12):3392–400.CrossRefPubMed
22.•
Amato MP et al. Neuropsychological features in childhood and juvenile multiple sclerosis: five-year follow-up. Neurology. 2014;83(16):1432–8. Large study demonstrating cognitive issues in at least one third of pediatric patients, and decline in some over a 5 year period.CrossRefPubMed
23.
Kerbrat A et al. Reduced head and brain size for age and disproportionately smaller thalami in child-onset MS. Neurology. 2012;78(3):194–201.CrossRefPubMed
24.
Chitnis T et al. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler. 2012;18(1):116–27.CrossRefPubMed
25.
Chitnis T. Disease-modifying therapy of pediatric multiple sclerosis. Neurotherapeutics. 2013;10(1):89–96.CrossRefPubMed
26.•
Chitnis T et al. International Pediatric MS Study Group Clinical Trials Summit: meeting report. Neurology. 2013;80(12):1161–8. This is a meeting report of U.S., European and Canadian regulatory agencies with clinicians, pharmaceutical representatives, discussing optimal trial design and outcomes in pediatric MS.CrossRefPubMedPubMedCentral
27.
Mikaeloff Y et al. Interferon-beta treatment in patients with childhood-onset multiple sclerosis. J Pediatr. 2001;139(3):443–6.CrossRefPubMed
28.
Ghezzi A et al. Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study. Mult Scler. 2005;11(4):420–4.CrossRefPubMed
29.
Pohl D et al. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology. 2005;64(5):888–90.CrossRefPubMed
30.
Ghezzi A et al. Treatment of early-onset multiple sclerosis with intramuscular interferonbeta-1a: long-term results. Neurol Sci. 2007;28(3):127–32.CrossRefPubMed
31.
Mikaeloff Y et al. Effectiveness of early beta interferon on the first attack after confirmed multiple sclerosis: a comparative cohort study. Eur J Paediatr Neurol. 2008;12(3):205–9.CrossRefPubMed
32.
Pakdaman H et al. Treatment of early onset multiple sclerosis with suboptimal dose of interferon beta-1a. Neuropediatrics. 2006;37(4):257–60.CrossRefPubMed
33.
Tenembaum SN et al. Subcutaneous interferon Beta-1a in pediatric multiple sclerosis: a retrospective study. J Child Neurol. 2013;28(7):849–56.CrossRefPubMed
34.
Korporal M et al. Interferon beta-induced restoration of regulatory T-cell function in multiple sclerosis is prompted by an increase in newly generated naive regulatory T cells. Arch Neurol. 2008;65(11):1434–9.CrossRefPubMed
35.
36.
Tenembaum SN, Segura MJ. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology. 2006;67(3):511–3.CrossRefPubMed
37.
38.
Banwell B et al. Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology. 2006;66(4):472–6.CrossRefPubMed
39.
Huppke P et al. Natalizumab use in pediatric multiple sclerosis. Arch Neurol. 2008;65(12):1655–8.CrossRefPubMed
40.
Putzki N et al. Natalizumab treatment in paediatric multiple sclerosis: a case of induction, de-escalation and escalation. Eur J Neurol. 2010;17(11):e105.PubMed
41.
Ghezzi A et al. Natalizumab in pediatric multiple sclerosis: results of a cohort of 55 cases. Mult Scler. 2013;19(8):1106–12.CrossRefPubMed
42.
Arnal-Garcia C et al. Natalizumab use in pediatric patients with relapsing-remitting multiple sclerosis. Eur J Paediatr Neurol. 2013;17(1):50–4.CrossRefPubMed
43.
Kornek B et al. Natalizumab therapy for highly active pediatric multiple sclerosis. JAMA Neurol. 2013;70(4):469–75.CrossRefPubMed
44.•
Ghezzi A et al. Natalizumab in the pediatric MS population: results of the Italian registry. BMC Neurol. 2015;15:174. Large observational study of 100+ pediatric MS patients treated with natalizumab.CrossRefPubMedPubMedCentral
45.
Gorelik L et al. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010;68(3):295–303.CrossRefPubMed
46.
Millefiorini E et al. Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol. 1997;244(3):153–9.CrossRefPubMed
47.
Edan G et al. Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: a randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry. 1997;62(2):112–8.CrossRefPubMedPubMedCentral
48.
Hartung HP et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet. 2002;360(9350):2018–25.CrossRefPubMed
49.
Martinelli V et al. Acute myeloid leukemia in Italian patients with multiple sclerosis treated with mitoxantrone. Neurology. 2011;77(21):1887–95.CrossRefPubMed
50.
Mulroy E et al. Long-term risk of leukaemia or cardiomyopathy after mitoxantrone therapy for multiple sclerosis. Eur Neurol. 2012;67(1):45–7.CrossRefPubMed
51.
Kornek B et al. Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis. Neuropediatrics. 2011;42(1):7–12.CrossRefPubMed
52.
Marriott JJ, Miyasaki J, Gronseth G, O’Connor PW, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Evidence report: the efficacy and safety of mitoxantrone (Novantrone) in the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2010;74:1463–70.CrossRefPubMedPubMedCentral
53.
D., O., Immunosuppressive treatments in multiple sclerosis. Handb Clin Neurol., 2014: p. p 122.
54.
55.
Cohen JA et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010;362(5):402–15.CrossRefPubMed
56.
Fragoso YD et al. Fingolimod prescribed for the treatment of multiple sclerosis in patients younger than age 18 years. Pediatr Neurol. 2015;53(2):166–8.CrossRefPubMed
57.
Gold R et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367(12):1098–107.CrossRefPubMed
58.
Fox RJ et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012;367(12):1087–97.CrossRefPubMed
59.
Hauser SL et al. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008;358(7):676–88.CrossRefPubMed
60.
Beres SJ, Graves J, Waubant E. Rituximab use in pediatric central demyelinating disease. Pediatr Neurol. 2014;51(1):114–8.CrossRefPubMed
61.
Nosadini M et al. Rituximab monitoring and redosing in pediatric neuromyelitis optica spectrum disorder. Neurol Neuroimmunol Neuroinflamm. 2016;3(1):e188.CrossRefPubMedPubMedCentral
62.
Salzer, J., et al., Rituximab in paediatric onset multiple sclerosis: a case series. J Neurol, 2015.
63.
Sheridan JP et al. Intermediate-affinity interleukin-2 receptor expression predicts CD56(bright) natural killer cell expansion after daclizumab treatment in the CHOICE study of patients with multiple sclerosis. Mult Scler. 2011;17(12):1441–8.CrossRefPubMed
64.
Phillips G et al. Assessing the impact of multiple sclerosis disease activity and daclizumab HYP treatment on patient-reported outcomes: results from the SELECT trial. Mult Scler Relat Disord. 2016;6:66–72.CrossRefPubMed
65.
Gorman MP, Tillema J, Ciliax AM, Guttmann CR, Chitnis T. Daclizumab use in patients with pediatric multiple sclerosis. Arch Neurol. 2012;69(1):78–81.CrossRefPubMed
66.
MacAllister WS et al. Fatigue and quality of life in pediatric multiple sclerosis. Mult Scler. 2009;15(12):1502–8.CrossRefPubMed
67.
Goretti B et al. Fatigue and its relationships with cognitive functioning and depression in paediatric multiple sclerosis. Mult Scler. 2012;18(3):329–34.CrossRefPubMed
68.
Parrish JB et al. Fatigue and depression in children with demyelinating disorders. J Child Neurol. 2013;28(6):713–8.CrossRefPubMed
69.
Zifko UA et al. Modafinil in treatment of fatigue in multiple sclerosis. Results of an open-label study. J Neurol. 2002;249(8):983–7.CrossRefPubMed
70.
Rammohan KW, Lynn DJ. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology. 2005;65(12):1995–7. author reply 1995-7.PubMed
71.
Stankoff B et al. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology. 2005;64(7):1139–43.CrossRefPubMed
72.
Volkow ND et al. Therapeutic doses of oral methylphenidate significantly increase extracellular dopamine in the human brain. J Neurosci. 2001;21(2):RC121.PubMed
73.
Prommer E. Methylphenidate: established and expanding roles in symptom management. Am J Hosp Palliat Care. 2012;29(6):483–90.CrossRefPubMed
74.
Mendonca DA, Menezes K, Jog MS. Methylphenidate improves fatigue scores in Parkinson disease: a randomized controlled trial. Mov Disord. 2007;22(14):2070–6.CrossRefPubMed
75.
Blockmans D et al. Does methylphenidate reduce the symptoms of chronic fatigue syndrome? Am J Med. 2006;119(2):167 e23–30.CrossRefPubMed
76.
77.
Phe V, Chartier-Kastler E, Panicker JN. Management of neurogenic bladder in patients with multiple sclerosis. Nat Rev Urol. 2016;13(5):275–88.CrossRefPubMed
78.
Tickner N et al. An overview of drug therapies used in the treatment of dystonia and spasticity in children. Arch Dis Child Educ Pract Ed. 2012;97(6):230–5.CrossRefPubMed
79.
80.
Malhotra T, Rosenzweig I. Baclofen withdrawal causes psychosis in otherwise unclouded consciousness. J Neuropsychiatry Clin Neurosci. 2009;21(4):476.CrossRefPubMed
81.
Houtchens MK et al. Open label gabapentin treatment for pain in multiple sclerosis. Mult Scler. 1997;3(4):250–3.CrossRefPubMed
82.
Rudick R et al. Recommendations from the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force. Ann Neurol. 1997;42(3):379–82.CrossRefPubMed
83.
Rudick RA, Cutter G, Baier M, Fisher E, Dougherty D, Weinstock-Guttman B, et al. Use of the Multiple Sclerosis Functional Composite to predict disability in relapsing MS. Neurology. 2001;56(10):1324–30.CrossRefPubMed
84.
Polman CH et al. Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis. Lancet Neurol. 2010;9(7):740–50.CrossRefPubMed
85.
Borriello G et al. Natalizumab treatment in pediatric multiple sclerosis: a case report. Eur J Paediatr Neurol. 2009;13(1):67–71.CrossRefPubMed
Metadaten
Titel
Use of Disease-Modifying Therapies in Pediatric MS
verfasst von
Marta Simone, MD
Tanuja Chitnis, MD
Publikationsdatum
01.08.2016
Verlag
Springer US
Erschienen in
Current Treatment Options in Neurology / Ausgabe 8/2016
Print ISSN: 1092-8480
Elektronische ISSN: 1534-3138
DOI
https://doi.org/10.1007/s11940-016-0420-7

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Neurologie

25.04.2024 | Hypotonie | Nachrichten

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 | AAN-Jahrestagung 2024 | Nachrichten

Frühe Alzheimertherapie lohnt sich

25.04.2024 | Parkinson-Krankheit | Nachrichten

Viel Bewegung in der Parkinsonforschung

23.04.2024 | Demenz | Nachrichten

Demenzkranke durch Antipsychotika vielfach gefährdet
weitere anzeigen

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise