Long-term follow-up of pediatric MS patients starting treatment with injectable first-line agents: A multicentre,Italian,retrospective,observational study

Abstract

Background:

Few data are available on very long-term follow-up of pediatric multiple sclerosis (MS) patients treated with disease modifying treatments (DMTs).

Objectives:

To present a long-term follow-up of a cohort of Pediatric-MS patients starting injectable first-line agents.

Methods:

Data regarding treatments, annualized relapse rate (ARR), Expanded Disability Status Scale (EDSS) score, and serious adverse event were collected. Baseline characteristics were tested in multivariate analysis to identify predictors of disease evolution.

Results:

In total, 97 patients were followed for 12.5 ± 3.3 years. They started therapy at 13.9 ± 2.1 years, 88 with interferons and 9 with copaxone. During the whole follow-up, 82 patients changed therapy, switching to immunosuppressors/second-line treatment in 58% of cases. Compared to pre-treatment phase, the ARR was significantly reduced during the first treatment (from 3.2 ± 2.6 to 0.7 ± 1.5, p < 0.001), and it remained low during the whole follow-up (0.3 ± 0.2, p < 0.001). At last observation, 40% had disability worsening, but EDSS score remained <4 in 89%. One patient died at age of 23 years due to MS. One case of natalizumab-related progressive multifocal encephalopathy (PML) was recorded. Starting therapy before 12 years of age resulted in a better course of disease in multivariate analysis.

Conclusion:

Pediatric-MS patients benefited from interferons/copaxone, but the majority had to switch to more powerful drugs. Starting therapy before 12 years of age could lead to a more favorable outcome.

Keywords

Pediatric multiple sclerosis long follow-up childhood child

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References

Waldman

Ghezzi

Bar-Or

et al . Multiple sclerosis in children: An update on clinical diagnosis, therapeutic strategies, and research. Lancet Neurol 2014; 13: 936–948.

Benson

Healy

Gorman

et al . Elevated relapse rates in pediatric compared to adult MS persist for at least 6 years. Mult Scler Relat Disord 2014; 3: 186–193.

Gorman

Healy

Polgar-Turcsanyi

et al . Increased relapse rate in pediatric-onset compared with adult-onset multiple sclerosis. Arch Neurol 2009; 66: 54–59.

Renoux

Vukusic

Mikaeloff

et al . Natural history of multiple sclerosis with childhood onset. N Engl J Med 2007; 356: 2603–2613.

Banwell

Reder

Krupp

et al . Safety and tolerability of interferon beta-1b in pediatric multiple sclerosis. Neurology 2006; 66: 472–476.

Ghezzi

Amato

Annovazzi

et al . Long-term results of immunomodulatory treatment in children and adolescents with multiple sclerosis: The Italian experience. Neurol Sci 2009; 30: 193–199.

Kornek

Bernert

Balassy

et al . Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis. Neuropediatrics 2003; 34: 120–126.

Krupp

Pohl

Ghezzi

et al . Subcutaneous interferon beta-1a in pediatric patients with multiple sclerosis: Regional differences in clinical features, disease management, and treatment outcomes in an international retrospective study. J Neurol Sci 2016; 363: 33–38.

Mikaeloff

Caridade

Tardieu

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.

10.

Mikaeloff

Moreau

Debouverie

et al . Interferon-beta treatment in patients with childhood-onset multiple sclerosis. J Pediatr 2001; 139: 443–446.

11.

Pohl

Rostasy

Gartner

et al . Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a. Neurology 2005; 64: 888–890.

12.

Tenembaum

Banwell

Pohl

et al . Subcutaneous interferon Beta-1a in pediatric multiple sclerosis: A retrospective study. J Child Neurol 2013; 28: 849–856.

13.

Tenembaum

Segura

MJ.

Interferon beta-1a treatment in childhood and juvenile-onset multiple sclerosis. Neurology 2006; 67: 511–513.

14.

Waubant

Hietpas

Stewart

et al . Interferon beta-1a in children with multiple sclerosis is well tolerated. Neuropediatrics 2001; 32: 211–213.

15.

Ghezzi

Amato

Makhani

et al . Pediatric multiple sclerosis: Conventional first-line treatment and general management. Neurology 2016; 87: S97–S102.

16.

Sizonenko

PC.

Physiology of puberty. J Endocrinol Invest 1989; 12: 59–63.

17.

Krupp

Tardieu

Amato

et al . 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: 1261–1267.

18.

Ghezzi

Moiola

Pozzilli

et al . Natalizumab in the pediatric MS population: Results of the Italian registry. BMC Neurol 2015; 15: 174.

19.

Kornek

Aboul-Enein

Rostasy

et al . Natalizumab therapy for highly active pediatric multiple sclerosis. JAMA Neurol 2013; 70: 469–475.

20.

Boiko

Vorobeychik

Paty

et al . Early onset multiple sclerosis: A longitudinal study. Neurology 2002; 59: 1006–1010.

21.

Harding

Liang

Cossburn

et al . Long-term outcome of paediatric-onset multiple sclerosis: A population-based study. J Neurol Neurosurg Psychiatry 2013; 84: 141–147.

22.

Huppke

Ellenberger

Rosewich

et al . Clinical presentation of pediatric multiple sclerosis before puberty. Eur J Neurol 2014; 21: 441–446.

23.

Ruggieri

Iannetti

Polizzi

et al . Multiple sclerosis in children under 10 years of age. Neurol Sci 2004; 25(Suppl. 4): S326–S335.

24.

Haliloglu

Anlar

Aysun

et al . Gender prevalence in childhood multiple sclerosis and myasthenia gravis. J Child Neurol 2002; 17: 390–392.

25.

Ghezzi

Clinical characteristics of multiple sclerosis with early onset. Neurol Sci 2004; 25(Suppl. 4): S336–S139.

26.

Yeh

Waubant

Krupp

et al . Multiple sclerosis therapies in pediatric patients with refractory multiple sclerosis. Arch Neurol 2011; 68: 437–444.

27.

Alroughani

Ahmed

Al-Hashel

Pediatric-onset multiple sclerosis disease progression in Kuwait: A retrospective analysis. Pediatr Neurol 2015; 53: 508–512.

28.

Deryck

Ketelaer

Dubois

Clinical characteristics and long term prognosis in early onset multiple sclerosis. J Neurol 2006; 253: 720–723.

29.

Ghezzi

Pozzilli

Liguori

et al . Prospective study of multiple sclerosis with early onset. Mult Scler 2002; 8: 115–118.

30.

Derle

Kurne

Konuskan

et al . Unfavorable outcome of pediatric onset multiple sclerosis: Follow-up in the pediatric and adult neurology departments of one referral center, in Turkey. Mult Scler Relat Disord 2016; 9: 1–4.

31.

Capra

Cordioli

Rasia

et al . Assessing long-term prognosis improvement as a consequence of treatment pattern changes in MS. Mult Scler 2017; 23: 1757–1761.

32.

Rocca

Absinta

Ghezzi

et al . Is a preserved functional reserve a mechanism limiting clinical impairment in pediatric MS patients? Hum Brain Mapp 2009; 30: 2844–2851.

33.

Brown

Narayanan

Banwell

et al . Magnetization transfer ratio recovery in new lesions decreases during adolescence in pediatric-onset multiple sclerosis patients. Neuroimage Clin 2014; 6: 237–242.

34.

Mikaeloff

Caridade

Assi

et al . Prognostic factors for early severity in a childhood multiple sclerosis cohort. Pediatrics 2006; 118: 1133–1139.

35.

Chabas

Ness

Belman

et al . Younger children with MS have a distinct CSF inflammatory profile at disease onset. Neurology 2010; 74: 399–405.

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