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  • Print publication year: 2011
  • Online publication date: April 2011

Chapter 10 - Disease-modifying therapy and response to first-line treatment in pediatric multiple sclerosis

from Section 2 - Pediatric MS Course and Treatment


Pediatric multiple sclerosis (MS), once considered a rare childhood illness, has been increasingly recognized as a disabling acquired pediatric neurological disease requiring early recognition and intervention. Males get affected with before puberty while females are more often hit around or after puberty. Race, ethnicity, and ancestry may also influence disease susceptibility and course differently. Epidemiological data clearly indicate that adult MS is a geographically related disease, with disease rates rising with an increased distance from the equator in both northern and southern hemispheres. A few candidates have been identified as associated with pediatric MS in a few epidemiological studies (neurotropic viruses, Chlamydia pneumonia, passive smoking). Seroepidemiologic and pathologic evidences have strongly suggested that prior infection with members of the Herpesviridae family may be associated with the development of MS in adulthood. The most studied member of the Herpesviridae family in MS patients has been Epstein-Barr virus (EBV).


1. 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;43:655–661.
2. JacobsL, CookfairDL, RudickRA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996;39:285–294.
3. PRISMS (Prevention of Relapses and Disability by Interferon β-1a subcutaneously in Multiple Sclerosis) Study Group. Randomized double-blind placebo-controlled study of interferon β-1a in relapsing/remitting multiple sclerosis. Lancet 1998;352:1498–1504.
4. Weinstock-GuttmanB, RansohoffRRM, KinkelRP, et al. The interferons: Biological effects mechanisms of action, and use in multiple sclerosis. Ann Neurol 1995;37:7–15.
5. YongV, ChabotS, StuveO, et al. Interferon beta in the treatment of multiple sclerosis. Mechanism of action. Neurology 1998;51:682–689.
6. European Study Group on interferon beta-1b in secondary progressive MS. Placebo-controlled multicentre randomised trial of interferon β-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998;352:1491–1497.
7. Secondary Progressive Efficacy Clinical trial of Recombinant Interferon-beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of recombinant interferon beta-1a in secondary progressive MS. Clinical results. Neurology 2001;56:1496–1504.
8. GoodkinD. and The North American Study Group on Interferon Beta-1b in Secondary Progressive MS. Interferon beta-1b in secondary progressive MS: Clinical and MRI results of a 3-year randomized controlled trial [Abstract]. Late Breaking News. Presented at the 52nd annual meeting of the American Academy of Neurology, San Diego, 2000.
9. CohenJ, CutterGR, FischerJS, et al. Benefit of interferon beta-1a on MSFC progression in secondary progressive MS. Neurology 2002;59:679–687.
10. PittockSJ, RodriguezM. Benign MS: A distinct clinical entity with therapeutic implications. In: Advances in Multiple Sclerosis, ed. M. Rodriguez. Heidelberg: Springer-Verlag, 2008. (Current Topics in Microbiology and Immunology, vol. 318); pp. 1–18.
11. TenembaumSN, SeguraMJ. Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology 2006;67:511–513.
12. MikaeloffY, MoreauT, DebouverieM, et al. Interferon-beta treatment in patients with childhood-onset multiple sclerosis. J Pediatr 2001;139:443–446.
13. BanwellB, RederAT, KruppL, et al. Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology 2006;66:472–476.
14. BykovaOV, KuzenkovaLM, MaslovaOI. [The use of beta-interferon-1b in children and adolescents with multiple sclerosis]. Zh Nevrol Psikhiatr Im S S Korsakova 2006;106:29–33.
15. PohlD, RostasyK, GartnerJ, et al. Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology, 2005. 64(5): pp. 888–90.
16. WaubantE, HietpasJ, StewartT, et al. Interferon beta-1a in children with multiple sclerosis is well tolerated. Neuropediatrics, 2001. 32(4): pp. 211–3.
17. GhezziA, AmatoMP, CapobiancoM, et al. Treatment of early-onset multiple sclerosis with intramuscular interferonbeta-1a: Long-term results. Neurol Sci 2007;28:127–132.
18. MikaeloffY, CaridadeG, TardieuM, et al. Effectiveness of early beta interferon on the first attack after confirmed multiple sclerosis: A comparative cohort study. Eur J Paediatr Neurol 2008;12:205–209.
19. PittockSJ. Does benign multiple sclerosis today imply benign multiple sclerosis tomorrow? Implications for treatment. Neurology 2007;68:480–481.
20. RamsaransingGS, De KeyserJ. Benign course in multiple sclerosis: A review. Acta Neurol Scand 2006;113:359–369.
21. PittockSJ, McClellandRL, MayrWT, et al. Clinical implications of benign multiple sclerosis: A 20-year population-based follow-up study. Ann Neurol 2004;56:303–306.
22. MalucchiS, SalaA, GilliF, et al. Neutralizing antibodies reduce the efficacy of betaIFN during treatment of multiple sclerosis. Neurology 2004;62:2031–2037.
23. PeriniP, CalabreseM, BiasiG, et al. The clinical impact of interferon beta antibodies in relapsing–remitting MS. J Neurol 2004;251:305–309.
24. ComiG, FilippiM, WolinskyJS. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging – Measured disease activity and burden in patients with relapsing multiple sclerosis. European/Canadian Glatiramer Acetate Study Group. Ann Neurol 2001;49:290–297.
25. CadavidD, WolanskyLJ, SkurnickJ, et al. Efficacy of treatment of MS with IFNbeta-1b or glatiramer acetate by monthly brain MRI in the BECOME study. Neurology 2009;72:1976–1983.
26. GhezziA. Immunomodulatory treatment of early onset multiple sclerosis: Results of an Italian Co-operative Study. Neurol Sci 2005;26(Suppl 4):S183–186.
27. GhezziA, AmatoMP, CapobiancoM, et al. Disease-modifying drugs in childhood-juvenile multiple sclerosis: Results of an Italian co-operative study. Mult Scler 2005;11:420–424.
28. KornekB, BernertG, BalassyC, et al. Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis. Neuropediatrics 2003;34:120–126.
29. YehE, KruppL, NessJ, et al. Breakthrough disease in pediatric MS patients: a pediatric network experience. In Annual Meeting of the American Academy of Neurology. 2009: Seattle, WA.
30. CohenBA, KhanO, JefferyDR, et al. Identifying and treating patients with suboptimal responses. Neurology 2004;63(Suppl 6):S33–40.
31. GormanMP, HealyBC, Polgar-TurcsanyiM, et al. Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol 2009;66:54–59.
32. BinquetC, QuantinC, Le TeuffG, et al. The prognostic value of initial relapses on the evolution of disability in patients with relapsing–remitting multiple sclerosis. Neuroepidemiology 2006;27:45–54.
33. PanitchH, GoodinDS, FrancisG, et al. Randomized, comparative study of interferon beta-1a treatment regimens in MS; The EVIDENCE Trial. Neurology 2002;359:1453–1460.
34. DurelliL, VerdunE, BarberoP, et al. Every other day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis; results of a 2-year prospective randomized multicenter study (INCOMIN). Lancet 2002;359:1453–1460.
35. IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: Experience during the first 3 years. Neurology 1996;47:889–894.
36. SorensenP, RossC, ClemmesenKM, et al. Clinical importance of neutralizing antibodies against interferon beta in patients with relapsing remitting multiple sclerosis. Lancet 2003;302:1184–1191.
37. CarraA, OnahaP, LueticG, et al. Therapeutic outcome 3 years after switching of immunomodulatory therapies in patients with relapsing–remitting multiple sclerosis in Argentina. Eur J Neurol 2008;15:386–393.
38. GajofattoA, BacchettiP, GrimesB, et al. Switching first-line disease-modifying therapy after failure: Impact on the course of relapsing–remitting multiple sclerosis. Mult Scler 2009;15:50–58.