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No evidence of disease activity including cognition (NEDA-3 plus) in naïve pediatric multiple sclerosis patients treated with natalizumab

Abstract

Background

Pediatric-onset multiple sclerosis (POMS) is characterized by high inflammatory activity, aggressive course and early development of physical and cognitive disability. A highly effective early treatment must be considered in POMS.

Objective

To evaluate safety and efficacy of natalizumab (NTZ) in naïve POMS.

Methods

20 naïve POMS (13F, 7 M; mean age: 13.8 ± 2.7 years) were treated with NTZ for at least 24 months (mean number of infusions: 42 ± 20). No evidence of disease activity (NEDA)-3 plus status, i.e., no relapse, no disease progression (EDSS score), no radiological activity and no cognitive decline, was evaluated.

Results

After 2 years of NTZ treatment, a significant reduction in the mean EDSS score (p < 0.0001) was observed in the whole cohort. During the follow-up, evidence of disease activity on MRI was observed in two patients (10%) and a mild decline in cognition was observed in other two. No patient had clinical relapse. At the time of last visit NEDA-3 plus status was maintained in 16 (80%) patients. No major adverse event was observed.

Conclusion

Early treatment of aggressive POMS with NTZ proved to be highly effective in achieving and maintaining the NEDA-3 plus status. Our data support the use of NTZ as first treatment choice in POMS.

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References

  1. 1.

    Ruet A (2018) Update on pediatric-onset multiple sclerosis. Rev Neurol (Paris) 174(6):398–407

  2. 2.

    Waldman A, Ness J, Pohl D et al (2016) Pediatric multiple sclerosis: clinical features and outcome. Neurology 87:S74–S81

  3. 3.

    Amato MP, Krupp LB, Charvet LE et al (2016) Pediatric multiple sclerosis: cognition and mood. Neurology 87:S82–S87

  4. 4.

    Baruch NF, O’Donneel EH, Glanz BI et al (2016) Cognitive and patient-reported outcomes in adults with pediatric-onset multiple sclerosis. Mult Scler 22(3):354–361

  5. 5.

    Ruano L, Branco M, Portaccio E et al (2018) Patients with pediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: an Italian collaborative study. Mult Scler 24(9):1234–1242

  6. 6.

    MacAllister WS, Belman AL, Milazzo M et al (2005) Cognitive functioning in children and adolescents with multiple sclerosis. Neurology 64:1422–1425

  7. 7.

    Banwell BL, Anderson PE (2005) The cognitive burden of multiple sclerosis in children. Neurology 64:891–894

  8. 8.

    Julian L, Serafin D, Charvet L et al (2013) Cognitive impairment occurs in children and adolescents with multiple sclerosis: results from a United States Network. J Child Neurol 28(1):102–107

  9. 9.

    Amato MP, Goretti B, Ghezzi A et al (2014) Neuropsychological features in childhood and juvenile multiple sclerosis: five-year follow-up. Neurology 83:1432–1438

  10. 10.

    Amato MP, Goretti B, Ghezzi A et al (2010) Cognitive and psychosocial features in childhood and juvenile MS: two-year follow-up. Neurology 75:1134–1140

  11. 11.

    Kornek B, Aboul-Enein F, Rostasy K et al (2013) Natalizumab therapy for highly active pediatric multiple sclerosis. JAMA Neurol 70:469–475

  12. 12.

    Arnal-Garcia C, Garcia-Montero MR, Malaga I et al (2013) Natalizumab use in pediatric patients with relapsing-remitting multiple sclerosis. Eur J Paediatr Neurol 17:50–54

  13. 13.

    Ghezzi A, Pozzilli C, Grimaldi LM et al (2013) Natalizumab in pediatric multiple sclerosis: results of a cohort of 55 cases. Mult Scler 19:1106–1112

  14. 14.

    Ghezzi A, Moiola L, Pozzilli C et al (2015) Natalizumab in the pediatric MS population: results of the Italian registry. BMC Neurol 15:174

  15. 15.

    Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–302

  16. 16.

    Giovannoni G, Turner B, Gnanapavan S, Offiah C, Schmjerer K, Marta M et al (2015) Is it time to target no evident disease activity (NEDA) in multiple sclerosis? Mult Scler Relat Disord 4(4):329–333

  17. 17.

    Río J, Nos C, Tintoré M, Téllez N, Galán I, Pelayo R et al (2006) Defining the response to interferon-beta in relapsing-remitting multiple sclerosis patients. Ann Neurol 59(2):344–352

  18. 18.

    Phillips JT, Giovannoni G, Lublin FD, O'Connor PW, Polman CH, Willoughby E et al (2011) Sustained improvement in Expanded Disability Status Scale as a new efficacy measure of neurological change in multiple sclerosis: treatment effects with natalizumab in patients with relapsing multiple sclerosis. Mult Scler 17(8):970–979

  19. 19.

    Pardini M, Uccelli A, Grafman J et al (2014) Isolated cognitive relapses in multiple sclerosis. J Neurol Neurosurg Psychiatry 85(9):1035–1037

  20. 20.

    Charvet L, Cleary R, Vazquez K et al (2014) Social cognition in pediatric-onset multiple sclerosis (MS). Mult Scleros J 20(11):1478–1484

  21. 21.

    Benedict R, DeLuca J, Enzinger C, Geurts J et al (2017) Neuropsychology of multiple sclerosis: looking back and moving forward. J Int Neuropsychol Soc 23(9–10):832–842

  22. 22.

    Mahad DH, Trapp BD, Lassmann H et al (2015) Pathological mechanisms in progressive multiple sclerosis. Lancet Neurol 14(2):183–193

  23. 23.

    Hutchinson M, Kappos L, Calabresi PA, for the AFFIRM, and SENTINEL Investigators et al (2009) The efficacy of natalizumab in patients with relapsing multiple sclerosis: subgroup analysis of AFFIRM and SENTINEL. J Neurol 256(3):405–415

  24. 24.

    McKay KA, Manouchehrinia A, Berrigan L et al (2019) Long-term cognitive outcomes in patients with pediatric-onset vs adult-onset multiple sclerosis. JAMA Neurol 201976(9):1028–1034

  25. 25.

    Kultzenigg Lassmann H (2008) Neuropathology of cognitive dysfunction in multiple sclerosis. Handb Clin Neurol 89:719–723

  26. 26.

    Chabas D, Castello-Trivino T, Mowry EM et al (2008) Vanishing MS T2-bright lesions before puberty: a distinct MRI phenotype. Neurology 71:1090–1093

  27. 27.

    Waubant E, Chabas D, Okuda D et al (2009) Difference in disease burden and activity in pediatric patients on brain magnetic resonance imaging at time of multiple sclerosis onset vs adults. Arch Neurol 66:967–971

  28. 28.

    Rocca MA, Absinta M, Ghezzi A et al (2009) Is a preserved functional reserve a mechanism limiting clinical impairment in pediatric MS patients? Hum Brain Mapp 30:2844–2851

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Author information

Correspondence to Monica Margoni.

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Conflicts of interest

Monica Margoni reports grants from Teva, grants from Genzyme Sanofi, grants from Merck Serono, grants from Biogen Idec, grants and personal fees from Novartis, during the conduct of the study. Francesca Rinaldi reports grants from Almirall, grants and personal fees from Teva, grants and personal fees from Genzyme Sanofi, grants and personal fees from Merck Serono, grants and personal fees from Biogen Idec, grants from Novartis, during the conduct of the study. Alice Riccardi has nothing to disclose. Silvia Franciotta has nothing to disclose. Paola Perini reports grants and personal fees from Merck Serono, grants and personal fees from Biogen Idec, grants and personal fees from Genzyme Sanofi, grants and personal fees from Bayer Schering Pharma, grants and personal fees from Novartis, grants and personal fees from Teva, during the conduct of the study. Paolo Gallo reports grants and personal fees from Merck Serono, grants and personal fees from Biogen Idec, grants and personal fees from Genzyme Sanofi, grants and personal fees from Bayer Schering Pharma, grants and personal fees from Novartis, grants and personal fees from Teva, grants from University of Padua, Department of Neurosciences DNS, grants from Veneto Region of Italy, grants from Italian Association for Multiple Sclerosis (AISM), grants from Italian Ministry of Public Health, during the conduct of the study.

Ethical standards

This study was approved by the local Ethics Committee and was performed according to the Declaration of Helsinki. Participants received an explanatory statement and gave their written informed consent to participate in the study.

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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 267, 100–105 (2020). https://doi.org/10.1007/s00415-019-09554-z

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Keywords

  • Pediatric-onset multiple sclerosis
  • Natalizumab
  • NEDA-3 plus