Current concepts in the treatment of multiple sclerosis in the pediatric population Review article
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Published:
Mar 31, 2022
Keywords:
multiple sclerosis, pediatric population, disease-modifying therapy in multiple sclerosis
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Abstract
Pediatric-onset multiple sclerosis belongs to the challenging issues of modern neurology both in the area of differential diagnostics and disease-modifying therapy. Treatment paradigms in children and adolescents with multiple sclerosis have been based mainly on data extrapolated from adult patients. However, in the last years significant progress has been achieved in the knowledge and clinical experience, including that from randomized clinical trials in pediatric population. This situation should result in the gradual improvement of long-term therapeutic effects in pediatric-onset multiple sclerosis patients.
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References
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13. McKay KA, Friberg E, Razaz N et al. Long-term Socioeconomic Outcomes Associated With Pediatric-Onset Multiple Sclerosis. JAMA Neurol. 2021; 78(4): 478-82.
14. Banwell B, Kennedy J, Sadovnick D et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology. 2009; 72(3): 232-9.
15. Weygandt M, Hummel HM, Schregel K et al. MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis. Neuroimage Clin. 2014; 7: 400-8.
16. De Meo E, Filippi M, Trojano M et al. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis. Ann Neurol. 2022; 91(4): 483-95.
17. Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol. 2019; 26(1): 27-40.
18. Filippi M, Danesi R, Derfuss T et al. Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis. J Neurol. 2022; 269(3): 1670-7.
19. Ghezzi A, Amato MP, Annovazzi P et al.; ITEMS (Immunomodulatory Treatment of Early-onset MS) Group. Long-term results of immunomodulatory treatment in children and adolescents with multiple sclerosis: the Italian experience. Neurol Sci. 2009; 30(3): 193-9.
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26. Margoni M, Rinaldi F, Miante S et al. Alemtuzumab following natalizumab in highly active paediatric-onset multiple sclerosis. Mult Scler J Exp Transl Clin. 2019; 5(3): 2055217319875471.
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28. Waubant E, Banwell B, Wassmer E et al.; IPMSSG. Clinical trials of disease-modifying agents in pediatric MS: Opportunities, challenges, and recommendations from the IPMSSG. Neurology. 2019; 92(22): e2538-e2549.
29. Schwartz CE, Grover SA, Powell VE et al. Risk factors for non-adherence to disease-modifying therapy in pediatric multiple sclerosis. Mult Scler. 2018; 24(2): 175-85.
30. Duffy LV, Sarill K, Forbes P et al. Shared Decision Making and Disease Modifying Therapy in Families of Children and Adolescents with Pediatric Onset Multiple Sclerosis. J Pediatr Nurs. 2021; 61: 404-9.
31. Chitnis T, Arnold DL, Banwell B et al.; PARADIGMS Study Group. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. N Engl J Med. 2018; 379(11): 1017-27.
32. Deiva K, Huppke P, Banwell B et al. Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS. J Neurol Neurosurg Psychiatry. 2020; 91(1): 58-66.
33. 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): 402-15.
34. Chitnis T, Banwell B, Kappos L et al.; TERIKIDS Investigators. Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial. Lancet Neurol. 2021; 20(12): 1001-11.
35. Sormani MP, Waubant E. Paediatric multiple sclerosis: a lesson from TERIKIDS. Lancet Neurol. 2021; 20(12): 971-3.
36. Jakimovski D, Awan S, Eckert SP et al. Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment. CNS Drugs. 2022; 36(1): 45-59.
37. Krysko KM, Graves JS, Rensel M et al.; US Network of Pediatric MS Centers. Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis. Ann Neurol. 2020; 88(1): 42-55.
38. Abdel-Mannan OA, Manchoon C, Rossor T et al.; UK-Childhood Inflammatory Disease Network. Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom. Neurol Neuroimmunol Neuroinflamm. 2021; 8(4): e1008.
39. Baroncini D, Simone M, Iaffaldano P et al.; Italian MS registry. Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis. JAMA Neurol. 2021; 78(6): 726-35.
40. Kopp TI, Blinkenberg M, Petersen T et al. Long term effect of delayed treatment on disability in patients with paediatric onset multiple sclerosis: A prospective Danish cohort study. Mult Scler Relat Disord. 2020; 40: 101956.
41. Iaffaldano P, Simone M, Lucisano G et al.; Italian iMedWeb Registry and the MSBase Registry. Prognostic indicators in pediatric clinically isolated syndrome. Ann Neurol. 2017; 81(5): 729-39.
42. He A, Merkel B, Brown JWL et al.; MSBase Study Group. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020; 19(4): 307-16.
43. Brown JWL, Coles A, Horakova D et al.; MSBase Study Group. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis. JAMA. 2019; 321(2): 175-87.
44. Margoni M, Rinaldi F, Riccardi A et al. No evidence of disease activity including cognition (NEDA-3 plus) in naïve pediatric multiple sclerosis patients treated with natalizumab. J Neurol. 2020; 267(1): 100-5.
45. De Meo E, Bonacchi R, Moiola L et al. Early Predictors of 9-Year Disability in Pediatric Multiple Sclerosis. Ann Neurol. 2021; 89(5): 1011-22.
46. Sandesjö F, Wassmer E, Deiva K et al. Current international trends in the treatment of multiple sclerosis in children-Impact of the COVID-19 pandemic. Mult Scler Relat Disord. 2021; 56: 103277.
2. Thompson AJ, Baranzini SE, Geurts J et al. Multiple sclerosis. Lancet. 2018; 391: 1622-36.
3. Stasiolek M. The role of selected immunoregulatory cell populations in autoimmune demyelination. Neuro Endocrinol Lett. 2011; 32(1): 25-33.
4. Stasiołek M. Agresywna postać stwardnienia rozsianego. Neurologia po Dyplomie. 2022; 3(17): 16-22.
5. Ruet A. Update on pediatric-onset multiple sclerosis. Rev Neurol (Paris). 2018; 174(6): 398-407.
6. Stasiołek M. Choroby demielinizacyjne OUN. In: Steinborn B (ed). Neurologia wieku rozwojowego. Wydawnictwo Lekarskie PZWL 2017: 83-108.
7. Chitnis T, Aaen G, Belman A et al.; US Network of Paediatric Multiple Sclerosis Centers. Improved relapse recovery in paediatric compared to adult multiple sclerosis. Brain. 2020; 143(9): 2733-41.
8. Otallah S, Banwell B. Pediatric Multiple Sclerosis: an Update. Curr Neurol Neurosci Rep. 2018; 18(11): 76.
9. Aubert-Broche B, Fonov V, Narayanan S et al.; Canadian Pediatric Demyelinating Disease Network. Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth. Neurology. 2014; 83(23): 2140-6.
10. 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): 2603-13.
11. McKay KA, Hillert J, Manouchehrinia A. Long-term disability progression of pediatric-onset multiple sclerosis. Neurology. 2019; 92(24): e2764-e2773.
12. Ruano L, Branco M, Portaccio E et al. Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: An Italian collaborative study. Mult Scler. 2018; 24(9): 1234-42.
13. McKay KA, Friberg E, Razaz N et al. Long-term Socioeconomic Outcomes Associated With Pediatric-Onset Multiple Sclerosis. JAMA Neurol. 2021; 78(4): 478-82.
14. Banwell B, Kennedy J, Sadovnick D et al. Incidence of acquired demyelination of the CNS in Canadian children. Neurology. 2009; 72(3): 232-9.
15. Weygandt M, Hummel HM, Schregel K et al. MRI-based diagnostic biomarkers for early onset pediatric multiple sclerosis. Neuroimage Clin. 2014; 7: 400-8.
16. De Meo E, Filippi M, Trojano M et al. Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis. Ann Neurol. 2022; 91(4): 483-95.
17. Dobson R, Giovannoni G. Multiple sclerosis – a review. Eur J Neurol. 2019; 26(1): 27-40.
18. Filippi M, Danesi R, Derfuss T et al. Early and unrestricted access to high-efficacy disease-modifying therapies: a consensus to optimize benefits for people living with multiple sclerosis. J Neurol. 2022; 269(3): 1670-7.
19. Ghezzi A, Amato MP, Annovazzi P et al.; ITEMS (Immunomodulatory Treatment of Early-onset MS) Group. Long-term results of immunomodulatory treatment in children and adolescents with multiple sclerosis: the Italian experience. Neurol Sci. 2009; 30(3): 193-9.
20. 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): 849-56.
21. 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): 116-27.
22. Krysko KM, Graves J, Rensel M et al.; US Network of Pediatric MS Centers. Use of newer disease-modifying therapies in pediatric multiple sclerosis in the US. Neurology. 2018; 91(19): e1778-e1787.
23. Alroughani R, Huppke P, Mazurkiewicz-Beldzinska M et al. Delayed-Release Dimethyl Fumarate Safety and Efficacy in Pediatric Patients With Relapsing-Remitting Multiple Sclerosis. Front Neurol. 2021; 11: 606418.
24. Ghezzi A, Moiola L, Pozzilli C et al.; MS Study Group-Italian Society of Neurology. Natalizumab in the pediatric MS population: results of the Italian registry. BMC Neurol. 2015; 15: 174.
25. Ghezzi A, Banwell B, Bar-Or A et al. Rituximab in patients with pediatric multiple sclerosis and other demyelinating disorders of the CNS: Practical considerations. Mult Scler. 2021; 27(12): 1814-22.
26. Margoni M, Rinaldi F, Miante S et al. Alemtuzumab following natalizumab in highly active paediatric-onset multiple sclerosis. Mult Scler J Exp Transl Clin. 2019; 5(3): 2055217319875471.
27. Stasiołek M, Połatyńska K. Przyszłość terapii stwardnienia rozsianego u dzieci i młodzieży. Child Neurology (Neurologia Dziecięca). 2015; 24(49): 37-44.
28. Waubant E, Banwell B, Wassmer E et al.; IPMSSG. Clinical trials of disease-modifying agents in pediatric MS: Opportunities, challenges, and recommendations from the IPMSSG. Neurology. 2019; 92(22): e2538-e2549.
29. Schwartz CE, Grover SA, Powell VE et al. Risk factors for non-adherence to disease-modifying therapy in pediatric multiple sclerosis. Mult Scler. 2018; 24(2): 175-85.
30. Duffy LV, Sarill K, Forbes P et al. Shared Decision Making and Disease Modifying Therapy in Families of Children and Adolescents with Pediatric Onset Multiple Sclerosis. J Pediatr Nurs. 2021; 61: 404-9.
31. Chitnis T, Arnold DL, Banwell B et al.; PARADIGMS Study Group. Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis. N Engl J Med. 2018; 379(11): 1017-27.
32. Deiva K, Huppke P, Banwell B et al. Consistent control of disease activity with fingolimod versus IFN β-1a in paediatric-onset multiple sclerosis: further insights from PARADIGMS. J Neurol Neurosurg Psychiatry. 2020; 91(1): 58-66.
33. 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): 402-15.
34. Chitnis T, Banwell B, Kappos L et al.; TERIKIDS Investigators. Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trial. Lancet Neurol. 2021; 20(12): 1001-11.
35. Sormani MP, Waubant E. Paediatric multiple sclerosis: a lesson from TERIKIDS. Lancet Neurol. 2021; 20(12): 971-3.
36. Jakimovski D, Awan S, Eckert SP et al. Multiple Sclerosis in Children: Differential Diagnosis, Prognosis, and Disease-Modifying Treatment. CNS Drugs. 2022; 36(1): 45-59.
37. Krysko KM, Graves JS, Rensel M et al.; US Network of Pediatric MS Centers. Real-World Effectiveness of Initial Disease-Modifying Therapies in Pediatric Multiple Sclerosis. Ann Neurol. 2020; 88(1): 42-55.
38. Abdel-Mannan OA, Manchoon C, Rossor T et al.; UK-Childhood Inflammatory Disease Network. Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom. Neurol Neuroimmunol Neuroinflamm. 2021; 8(4): e1008.
39. Baroncini D, Simone M, Iaffaldano P et al.; Italian MS registry. Risk of Persistent Disability in Patients With Pediatric-Onset Multiple Sclerosis. JAMA Neurol. 2021; 78(6): 726-35.
40. Kopp TI, Blinkenberg M, Petersen T et al. Long term effect of delayed treatment on disability in patients with paediatric onset multiple sclerosis: A prospective Danish cohort study. Mult Scler Relat Disord. 2020; 40: 101956.
41. Iaffaldano P, Simone M, Lucisano G et al.; Italian iMedWeb Registry and the MSBase Registry. Prognostic indicators in pediatric clinically isolated syndrome. Ann Neurol. 2017; 81(5): 729-39.
42. He A, Merkel B, Brown JWL et al.; MSBase Study Group. Timing of high-efficacy therapy for multiple sclerosis: a retrospective observational cohort study. Lancet Neurol. 2020; 19(4): 307-16.
43. Brown JWL, Coles A, Horakova D et al.; MSBase Study Group. Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis. JAMA. 2019; 321(2): 175-87.
44. Margoni M, Rinaldi F, Riccardi A et al. No evidence of disease activity including cognition (NEDA-3 plus) in naïve pediatric multiple sclerosis patients treated with natalizumab. J Neurol. 2020; 267(1): 100-5.
45. De Meo E, Bonacchi R, Moiola L et al. Early Predictors of 9-Year Disability in Pediatric Multiple Sclerosis. Ann Neurol. 2021; 89(5): 1011-22.
46. Sandesjö F, Wassmer E, Deiva K et al. Current international trends in the treatment of multiple sclerosis in children-Impact of the COVID-19 pandemic. Mult Scler Relat Disord. 2021; 56: 103277.