Neuropediatrics 2013; 44(06): 309-313
DOI: 10.1055/s-0033-1359308
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Treatment of Pediatric Multiple Sclerosis

Barbara Kornek
1   Department of Neurology, Medical University of Vienna, Vienna, Austria
› Author Affiliations
Further Information

Publication History

20 August 2013

29 September 2013

Publication Date:
07 November 2013 (online)

Abstract

Multiple sclerosis (MS) in children and adolescents has received increased attention during the past decade. Although not tested in randomized placebo-controlled trials, first-line disease-modifying therapies are widely used in patients with MS who are younger than 18 years. This review summarizes current treatment practices, possible future treatment options, and gives insight into special problems in the treatment of pediatric patients with MS.

 
  • References

  • 1 Boiko A, Vorobeychik G, Paty D, Devonshire V, Sadovnick D. University of British Columbia MS Clinic Neurologists Early onset multiple sclerosis: a longitudinal study. Neurology 2002; 59 (7) 1006-1010
  • 2 Simone IL, Carrara D, Tortorella C , et al. Course and prognosis in early-onset MS: comparison with adult-onset forms. Neurology 2002; 59 (12) 1922-1928
  • 3 Renoux C, Vukusic S, Mikaeloff Y , et al; Adult Neurology Departments KIDMUS Study Group. Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007; 356 (25) 2603-2613
  • 4 Venkateswaran S, Banwell B. Pediatric multiple sclerosis. Neurologist 2010; 16 (2) 92-105
  • 5 Banwell B, Ghezzi A, Bar-Or A, Mikaeloff Y, Tardieu M. Multiple sclerosis in children: clinical diagnosis, therapeutic strategies, and future directions. Lancet Neurol 2007; 6 (10) 887-902
  • 6 Ruggieri M, Iannetti P, Polizzi A, Pavone L, Grimaldi LM. Italian Society of Paediatric Neurology Study Group on Childhood Multiple Sclerosis. Multiple sclerosis in children under 10 years of age. Neurol Sci 2004; 25 (Suppl. 04) S326-S335
  • 7 Gorman MP, Healy BC, Polgar-Turcsanyi M, Chitnis T. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol 2009; 66 (1) 54-59
  • 8 Julian L, Serafin D, Charvet L , et al; Network of Pediatric MS Centers of Excellence. Cognitive impairment occurs in children and adolescents with multiple sclerosis: results from a United States network. J Child Neurol 2013; 28 (1) 102-107
  • 9 Amato MP, Goretti B, Ghezzi A , et al; Multiple Sclerosis Study Group of the Italian Neurological Society. Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up. Neurology 2010; 75 (13) 1134-1140
  • 10 Banwell B. Treatment of children and adolescents with multiple sclerosis. Expert Rev Neurother 2005; 5 (3) 391-401
  • 11 Pohl D, Waubant E, Banwell B , et al; International Pediatric MS Study Group. Treatment of pediatric multiple sclerosis and variants. Neurology 2007; 68 (16) (Suppl. 02) S54-S65
  • 12 Ghezzi A, Banwell B, Boyko A , et al. The management of multiple sclerosis in children: a European view. Mult Scler 2010; 16 (10) 1258-1267
  • 13 Ghezzi A. Therapeutic strategies in childhood multiple sclerosis. Ther Adv Neurol Disord 2010; 3 (4) 217-228
  • 14 Banwell B, Bar-Or A, Giovannoni G, Dale RC, Tardieu M. Therapies for multiple sclerosis: considerations in the pediatric patient. Nat Rev Neurol 2011; 7 (2) 109-122
  • 15 Chitnis T, Tenembaum S, Banwell B , et al; International Pediatric Multiple Sclerosis Study Group. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult Scler 2012; 18 (1) 116-127
  • 16 Johnston J, So TY. First-line disease-modifying therapies in paediatric multiple sclerosis: a comprehensive overview. Drugs 2012; 72 (9) 1195-1211
  • 17 Chitnis T. Disease-modifying therapy of pediatric multiple sclerosis. Neurotherapeutics 2013; 10 (1) 89-96
  • 18 Goodin DS, Frohman EM, Garmany Jr GP , et al; Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Disease modifying therapies in multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002; 58 (2) 169-178
  • 19 Compston A, Coles A. Multiple sclerosis. Lancet 2002; 359 (9313) 1221-1231
  • 20 Optic Neuritis Study Group. The 5-year risk of MS after optic neuritis. Experience of the optic neuritis treatment trial. Neurology 1997; 49 (5) 1404-1413
  • 21 Waldman AT, Gorman MP, Rensel MR, Austin TE, Hertz DP, Kuntz NL ; Network of Pediatric Multiple Sclerosis Centers of Excellence of National Multiple Sclerosis Society. Management of pediatric central nervous system demyelinating disorders: consensus of United States neurologists. J Child Neurol 2011; 26 (6) 675-682
  • 22 Weinshenker BG, O'Brien PC, Petterson TM , et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999; 46 (6) 878-886
  • 23 Takahashi I, Sawaishi Y, Takeda O, Enoki M, Takada G. Childhood multiple sclerosis treated with plasmapheresis. Pediatr Neurol 1997; 17 (1) 83-87
  • 24 The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 1993; 43 (4) 655-661
  • 25 Jacobs LD, Cookfair DL, Rudick RA , et al; The Multiple Sclerosis Collaborative Research Group (MSCRG). Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996; 39 (3) 285-294
  • 26 Group PRISMS. Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet 1998; 352 (9139) 1498-1504
  • 27 Johnson KP, Brooks BR, Cohen JA , et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 1995; 45 (7) 1268-1276
  • 28 Jacobs LD, Beck RW, Simon JH , et al; CHAMPS Study Group. Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000; 343 (13) 898-904
  • 29 Comi G, Filippi M, Barkhof F , et al; Early Treatment of Multiple Sclerosis Study Group. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357 (9268) 1576-1582
  • 30 Kappos L, Freedman MS, Polman CH , et al; BENEFIT Study Group. Effect of early versus delayed interferon beta-1b treatment on disability after a first clinical event suggestive of multiple sclerosis: a 3-year follow-up analysis of the BENEFIT study. Lancet 2007; 370 (9585) 389-397
  • 31 Comi G, Martinelli V, Rodegher M , et al; PreCISe study group. 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 (9700) 1503-1511
  • 32 Filippini G, Del Giovane C, Vacchi L , et al. Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis. (Review) Cochrane Database Syst Rev 2013; 6: CD008933
  • 33 Ebers GC, Reder AT, Traboulsee A , et al; Investigators of the 16-Year Long-Term Follow-Up Study. Long-term follow-up of the original interferon-beta1b trial in multiple sclerosis: design and lessons from a 16-year observational study. Clin Ther 2009; 31 (8) 1724-1736
  • 34 Bermel RA, Weinstock-Guttman B, Bourdette D, Foulds P, You X, Rudick RA. Intramuscular interferon beta-1a therapy in patients with relapsing-remitting multiple sclerosis: a 15-year follow-up study. Mult Scler 2010; 16 (5) 588-596
  • 35 Kappos L, Traboulsee A, Constantinescu C , et al. Long-term subcutaneous interferon beta-1a therapy in patients with relapsing-remitting MS. Neurology 2006; 67 (6) 944-953
  • 36 Ford C, Goodman AD, Johnson K , et al. Continuous long-term immunomodulatory therapy in relapsing multiple sclerosis: results from the 15-year analysis of the US prospective open-label study of glatiramer acetate. Mult Scler 2010; 16 (3) 342-350
  • 37 Goodin DS, Ebers GC, Cutter G , et al. Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFNβ-1b study. BMJ Open 2012; 2 (6) e001972
  • 38 Mikaeloff Y, Moreau T, Debouverie M , et al. Interferon-beta treatment in patients with childhood-onset multiple sclerosis. J Pediatr 2001; 139 (3) 443-446
  • 39 Waubant E, Hietpas J, Stewart T , et al. Interferon beta-1a in children with multiple sclerosis is well tolerated. Neuropediatrics 2001; 32 (4) 211-213
  • 40 Pohl D, Rostasy K, Gärtner J, Hanefeld F. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology 2005; 64 (5) 888-890
  • 41 Ghezzi A, Amato MP, Capobianco M , et al; Immunomodulatory Treatment of Early onset MS Group. Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study. Mult Scler 2005; 11 (4) 420-424
  • 42 Ghezzi A, Amato MP, Capobianco M , et al; Immunomodulatory Treatment of Early-onset MS (ITEMS) Group. Treatment of early-onset multiple sclerosis with intramuscular interferonbeta-1a: long-term results. Neurol Sci 2007; 28 (3) 127-132
  • 43 Banwell B, Reder AT, Krupp L , et al. Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology 2006; 66 (4) 472-476
  • 44 Tenembaum SN, Segura MJ. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology 2006; 67 (3) 511-513
  • 45 Mikaeloff Y, Caridade G, Tardieu M, Suissa S ; KIDSEP study group of the French Neuropediatric Society. Effectiveness of early beta interferon on the first attack after confirmed multiple sclerosis: a comparative cohort study. Eur J Paediatr Neurol 2008; 12 (3) 205-209
  • 46 Tenembaum SN, Banwell B, Pohl D , et al; REPLAY Study Group. Subcutaneous interferon Beta-1a in pediatric multiple sclerosis: a retrospective study. J Child Neurol 2013; 28 (7) 849-856
  • 47 Kornek B, Bernert G, Balassy C, Geldner J, Prayer D, Feucht M. Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis. Neuropediatrics 2003; 34 (3) 120-126
  • 48 Krupp LB, Banwell B, Tenembaum S ; International Pediatric MS Study Group. Consensus definitions proposed for pediatric multiple sclerosis and related disorders. Neurology 2007; 68 (16) (Suppl. 02) S7-S12
  • 49 Krupp LB, Tardieu M, Amato MP , et al; International Pediatric Multiple Sclerosis Study Group. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult Scler 2013; 19 (10) 1261-1267
  • 50 Polman CH, Reingold SC, Banwell B , et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 2011; 69 (2) 292-302
  • 51 Yeh EA, Waubant E, Krupp LB , et al; National Network of Pediatric MS Centers of Excellence. Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis. Arch Neurol 2011; 68 (4) 437-444
  • 52 Polman CH, O'Connor PW, Havrdova E , et al; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354 (9) 899-910
  • 53 Rudick RA, Stuart WH, Calabresi PA , et al; SENTINEL Investigators. Natalizumab plus interferon beta-1a for relapsing multiple sclerosis. N Engl J Med 2006; 354 (9) 911-923
  • 54 Huppke P, Stark W, Zürcher C, Huppke B, Brück W, Gärtner J. Natalizumab use in pediatric multiple sclerosis. Arch Neurol 2008; 65 (12) 1655-1658
  • 55 Borriello G, Prosperini L, Luchetti A , et al. Natalizumab treatment in pediatric multiple sclerosis: a case report. Eur J Paediatr Neurol 2009; 13: 76-71
  • 56 Ghezzi A, Pozzilli C, Grimaldi LM , et al. Safety and efficacy of natalizumab in children with multiple sclerosis. Neurology 2010; 75 (10) 912-917
  • 57 Ghezzi A, Pozzilli C, Grimaldi LME , et al; Italian MS Study Group. Natalizumab in pediatric multiple sclerosis: results of a cohort of 55 cases. Mult Scler 2013; 19 (8) 1106-1112
  • 58 Kornek B, Aboul-Enein F, Rostasy K , et al. Natalizumab therapy for highly active pediatric multiple sclerosis. JAMA Neurol 2013; 70 (4) 469-475
  • 59 Bloomgren G, Richman S, Hotermans C , et al. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med 2012; 366 (20) 1870-1880
  • 60 Kappos L, Bates D, Edan G , et al. Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring. Lancet Neurol 2011; 10 (8) 745-758
  • 61 Sørensen PS, Bertolotto A, Edan G , et al. Risk stratification for progressive multifocal leukoencephalopathy in patients treated with natalizumab. Mult Scler 2012; 18 (2) 143-152
  • 62 Bozic C, Richman S, Plavina T. Prevalence of anti-JCV antibodies in MS patients receiving or considering treatment with natalizumab: baseline results of STRATIFY-1. Neurology 2011; 76 (Suppl. 04) A598
  • 63 Trampe AK, Hemmelmann C, Stroet A , et al. Anti-JC virus antibodies in a large German natalizumab-treated multiple sclerosis cohort. Neurology 2012; 78 (22) 1736-1742
  • 64 Kappos L, Radue EW, O'Connor P , et al; FREEDOMS Study Group. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010; 362 (5) 387-401
  • 65 Cohen JA, Barkhof F, Comi G , et al; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010; 362 (5) 402-415
  • 66 Oh J, O'Connor PW. Safety, tolerability, and efficacy of oral therapies for relapsing-remitting multiple sclerosis. CNS Drugs 2013; 27 (8) 591-609
  • 67 FDA. Gilenya (fingolimod): drug safety communication-safety review of a reported death after the first dose. 2011 , updated 2012. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsfor HumanMedicalProducts/ucm284355.htm
  • 68 Makhani N, Gorman MP, Branson HM, Stazzone L, Banwell BL, Chitnis T. Cyclophosphamide therapy in pediatric multiple sclerosis. Neurology 2009; 72 (24) 2076-2082
  • 69 Hartung HP, Gonsette R, König N , et al; Mitoxantrone in Multiple Sclerosis Study Group (MIMS). Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 2002; 360 (9350) 2018-2025
  • 70 Kornek B, Bernert G, Rostasy K , et al. Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis. Neuropediatrics 2011; 42 (1) 7-12
  • 71 Fox RJ, Miller DH, Phillips JT , et al; CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012; 367 (12) 1087-1097
  • 72 Gold R, Kappos L, Arnold DL , et al; DEFINE Study Investigators. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med 2012; 367 (12) 1098-1107
  • 73 Ermis U, Wiesmann M, Nolte K , et al. Fumaric acid-associated progressive multifocal leukencephalopathy (PML), treatment and survival in a patient with psoriasis. (published online: September 30, 2011). Kongress der Deutschen Gesellschaft für Neurologie. 2011
  • 74 van Oosten BW, Killestein J, Barkhof F, Polman CH, Wattjes MP. PML in a patient treated with dimethyl fumarate from a compounding pharmacy. N Engl J Med 2013; 368 (17) 1658-1659
  • 75 O'Connor P, Wolinsky JS, Confavreux C , et al; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med 2011; 365 (14) 1293-1303
  • 76 Kappos L , ed. The efficacy and safety of teriflunomide in patients with relapsing MS: results from TOWER: a phase III, placebo-controlled study (Presentation 153). ECTRIMS, Lyon, France 2012
  • 77 Comi G, Jeffery D, Kappos L , et al; ALLEGRO Study Group. Placebo-controlled trial of oral laquinimod for multiple sclerosis. N Engl J Med 2012; 366 (11) 1000-1009
  • 78 Comi G, Vollmer T, Sorensen S , et al. Pooled analyses from the ALLEGRO and BRAVO trials on the safety and tolerability of laquinimod as a multiple sclerosis treatment (P04.132). American Academy of Neurology, New Orleans, USA; 2012
  • 79 Hauser SL, Waubant E, Arnold DL , et al; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med 2008; 358 (7) 676-688
  • 80 Carson KR, Evens AM, Richey EA , et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood 2009; 113 (20) 4834-4840
  • 81 Tzaribachev N, Koetter I, Kuemmerle-Deschner JB, Schedel J. Rituximab for the treatment of refractory pediatric autoimmune diseases: a case series. Cases J 2009; 2: 6609
  • 82 Cohen JA, Coles AJ, Arnold DL , et al; CARE-MS I investigators. 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 (9856) 1819-1828
  • 83 Coles AJ, Twyman CL, Arnold DL , et al; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet 2012; 380 (9856) 1829-1839
  • 84 Wynn D, Kaufman M, Montalban X , et al; CHOICE investigators. Daclizumab in active relapsing multiple sclerosis (CHOICE study): a phase 2, randomised, double-blind, placebo-controlled, add-on trial with interferon beta. Lancet Neurol 2010; 9 (4) 381-390
  • 85 Gold R, Giovannoni G, Selmaj K , et al. Daclizumab high-yield process in relapsing-remitting multiple sclerosis (SELECT): a randomised, double-blind, placebo-controlled trial. Lancet 2013; 381 (9884) 2167-2175
  • 86 Gorman MP, Tillema JM, Ciliax AM, Guttmann CR, Chitnis T. Daclizumab use in patients with pediatric multiple sclerosis. Arch Neurol 2012; 69 (1) 78-81
  • 87 Menzin J, Caon C, Nichols C, White LA, Friedman M, Pill MW. Narrative review of the literature on adherence to disease-modifying therapies among patients with multiple sclerosis. J Manag Care Pharm 2013; 19 (1, Suppl A ): S24-S40