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Multiple sclerosis
Original research
Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry
  1. Sifat Sharmin1,
  2. Charles B Malpas1,2,
  3. Izanne Roos1,2,
  4. Ibrahima Diouf1,
  5. Raed Alroughani3,
  6. Serkan Ozakbas4,
  7. Guillermo Izquierdo5,
  8. Sara Eichau5,
  9. Dana Horakova6,
  10. Eva K Havrdova6,
  11. Francesco Patti7,
  12. Murat Terzi8,
  13. Cavit Boz9,
  14. Bassem Yamout10,11,
  15. Samia J Khoury10,
  16. Marco Onofrj12,
  17. Alessandra Lugaresi13,14,
  18. Ayse Altintas15,
  19. Alexandre Prat16,
  20. Marc Girard16,
  21. Pierre Duquette16,
  22. Maria José Sá17,
  23. Daniele La Spitaleri18,
  24. Youssef Sidhom19,
  25. Riadh Gouider19,
  26. Saloua Mrabet20,
  27. Aysun Soysal21,
  28. Recai Turkoglu22,
  29. Maria Pia Amato23,
  30. Yara D Fragoso24,
  31. Tomas Kalincik1,2
  1. 1 CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
  2. 2 Neuroimmunology, Department of Neurology, The Royal Melbourne Hospital, Melbourne, Victoria, Australia
  3. 3 Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait
  4. 4 Faculty of Medicine, Dokuz Eylul University, İzmir, Turkey
  5. 5 Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena, Sevilla, Spain
  6. 6 Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic
  7. 7 Department of Medical and Surgical Sciences and Advanced Technologies, Multiple Sclerosis Center, University of Catania, Catania, Italy
  8. 8 Medical Faculty, 19 Mayis University, Samsun, Turkey
  9. 9 Department of Neurology, Karadeniz Technical University, Trabzon, Turkey
  10. 10 Nehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon
  11. 11 Neurology Department, American University of Beirut, Beirut, Lebanon
  12. 12 Department of Neuroscience, Imaging, and Clinical Sciences, University G. d’Annunzio, Chieti, Italy
  13. 13 UOSI Riabilitazione Sclerosi Multipla, IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy
  14. 14 Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy
  15. 15 Department of Neurology, School of Medicine, Koc University, Istanbul, Turkey
  16. 16 CHUM MS Center and Department of Neuroscience, Faculty of Medicine, Université de Montréal, Montréal, Quebec, Canada
  17. 17 Department of Neurology, Centro Hospitalar Universitario de Sao Joao, Porto, Portugal
  18. 18 Department of Neurology, AORN San Giuseppe Moscati, Avellino, Italy
  19. 19 Department of Neurology, Razi Hospital, Manouba, Tunisia
  20. 20 Clinical Investigation Center Neurosciences and Mental Health, Faculty of Medicine, University Tunis El Manar, Tunis, Tunisia
  21. 21 Department of Neurology, Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey
  22. 22 Department of Neurology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey
  23. 23 Department NEUROFARBA, University of Florence, Florence, Italy
  24. 24 Department of Neurology, Universidade Metropolitana de Santos, Santos, Brazil
  1. Correspondence to Professor Tomas Kalincik, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia; tomas.kalincik{at}unimelb.edu.au

Abstract

Background Early recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time.

Objective To identify early predictors of rapid disability accrual in patients with paediatric-onset MS.

Methods Using the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms. The clinico-demographic characteristics examined as predictors of future MS Severity Score (MSSS) included sex, age at symptom onset, absence of disability at the initial assessment, maximum Expanded Disability Status Scale (EDSS) score, relapse frequency and presence of brainstem, pyramidal, visual or cerebellar symptoms in the first year. A Bayesian log-normal generalised linear mixed model adjusted for cumulative proportion of time on higher-efficacy disease-modifying therapies (DMTs) was used to analyse the data.

Results 672 patients (70% female) contributing 9357 visits were included. The median age at symptom onset was 16 (quartiles 15–17) years. Older age at symptom onset (exp(β)=1.10 (95% CI 1.04 to 1.17)), higher EDSS score (1.22 (1.12 to 1.34)) and pyramidal (1.31 (1.11 to 1.55)), visual (1.25 (1.10 to 1.44)) or cerebellar (1.18 (1.01 to 1.38)) symptoms in the first year were associated with higher MSSS. MSSS was reduced by 4% for every 24% increase in the proportion of time on higher-efficacy DMTs (0.96 (0.93 to 0.99)).

Conclusions A relatively later onset of MS in childhood, higher disability and pyramidal, visual or cerebellar symptoms during the first year predicted significant worsening in disability in patients with paediatric-onset MS. Persistent treatment with higher-efficacy DMTs was associated with a reduced rate of disability worsening.

  • multiple sclerosis
  • neuroepidemiology
  • neuroimmunology
  • paediatric neurology

Data availability statement

MSBase is a data processor and warehouses data from individual principal investigators who agree to share their data sets on a project-by-project basis. Each principal investigator will need to be approached individually for permission to access the data sets.

https://doi.org/10.1136/jnnp-2022-329713

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    Data availability statement

    MSBase is a data processor and warehouses data from individual principal investigators who agree to share their data sets on a project-by-project basis. Each principal investigator will need to be approached individually for permission to access the data sets.

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    Footnotes

    • Twitter @saloua_mrabet

    • Contributors SS conceptualised and designed the study, carried out statistical analyses, interpreted the results, and have drafted and edited the manuscript. TK conceptualised and designed the study, contributed data, interpreted the results and have edited the manuscript. CBM and ID contributed to the concept of the study, interpreted the results and have edited the manuscript. IR contributed to the concept of the study, contributed data, interpreted the results and have edited the manuscript. RA, SO, GI, SE, DH, EKH, FP, MT, CB, BY, SJK, MO, AL, AA, AP, MG, PD, MJS, DLS, YS, RG, AS, RT, MPA and YDF recruited patients, contributed data, interpreted the results and have edited the manuscript. SS and TK are responsible for the overall content as the gurantors.

    • Funding This study was conducted separately and apart from the guidance of the funding source. The corresponding authors confirm that they had full access to all the data in the study and had final responsibility for the decision to submit for publication.

    • Map disclaimer The inclusion of any map (including the depiction of any boundaries therein), or of any geographic or locational reference, does not imply the expression of any opinion whatsoever on the part of BMJ concerning the legal status of any country, territory, jurisdiction or area or of its authorities. Any such expression remains solely that of the relevant source and is not endorsed by BMJ. Maps are provided without any warranty of any kind, either express or implied.

    • Competing interests SS has nothing to disclose. CM has nothing to disclose. IR served on scientific advisory boards, received conference travel support and/or speaker honoraria from Roche, Novartis, Merck and Biogen. ID has nothing to disclose. RA received honoraria as a speaker and for serving on scientific advisory boards from Bayer, Biogen, GSK, Merck, Novartis, Roche and Sanofi-Genzyme. SO has nothing to disclose. GI received speaking honoraria from Biogen, Novartis, Sanofi, Merck, Roche, Almirall and Teva. SE received speaker honoraria and consultant fees from Biogen Idec, Novartis, Merck, Bayer, Sanofi Genzyme, Roche and Teva. DH received speaker honoraria and consulting fees from Biogen, Merck, Teva, Roche, Sanofi Genzyme and Novartis, as well as support for research activities from Biogen and Czech Ministry of Education (project Progres Q27/LF1). EKH received honoraria/research support from Biogen, Merck Serono, Novartis, Roche and Teva; has been a member of advisory boards for Actelion, Biogen, Celgene, MS, Novartis and SG; and has been supported by the Czech Ministry of Education research project PROGRES Q27/LF1. FP received speaker honoraria and advisory board fees from Almirall, Bayer, Biogen, Celgene, Merck, Novartis, Roche, Sanofi-Genzyme and TEVA. He received research funding from Biogen, Merck, FISM (Fondazione Italiana Sclerosi Multipla), Reload Onlus Association and University of Catania. MT received travel grants from Novartis, Bayer-Schering, Merck and Teva; and has participated in clinical trials by Sanofi Aventis, Roche and Novartis. CB received conference travel support from Biogen, Novartis, Bayer-Schering, Merck and Teva; and has participated in clinical trials by SA, Roche and Novartis. BY has nothing to disclose. SJK received personal compensation for participation in the Roche MaeStro Exchange Program and in Merck-Serono medical advisory board. MO has nothing to disclose. AL has received personal compensation for consulting, serving on a scientific advisory board, speaking or other activities from Biogen, Bristol Myers Squibb, Merck Serono, Mylan, Novartis, Roche, Sanofi/Genzyme and Teva. Her institutions have received research grants from Novartis (last 4 years). AA received personal fees and speaker honoraria from Teva, Merck, Biogen - Gen Pharma, Roche, Novartis, Bayer and Sanofi-Genzyme; and received travel and registration grants from Merck, Biogen - Gen Pharma, Roche, Sanofi-Genzyme and Bayer. AP has nothing to disclose. MG received consulting fees from Teva Canada Innovation, Biogen, Novartis and Genzyme Sanofi; and lecture payments from Teva Canada Innovation, Novartis and EMD. He has also received a research grant from Canadian Institutes of Health Research. PD served on editorial boards and has been supported to attend meetings by EMD, Biogen, Novartis, Genzyme and TEVA Neuroscience. He holds grants from the CIHR and the MS Society of Canada and has received funding for investigator-initiated trials from Biogen, Novartis and Genzyme. MJS has nothing to disclose. DS received honoraria as a consultant on scientific advisory boards by Bayer-Schering, Novartis and Sanofi-Aventis and compensation for travel from Novartis, Biogen, Sanofi Aventis, Teva and Merck. YS has nothing to disclose. RG has nothing to disclose. AS has nothing to disclose. RT has nothing to disclose. MPA received honoraria as a consultant on scientific advisory boards by Biogen, Bayer-Schering, Merck, Teva and Sanofi-Aventis; and has received research grants by Biogen, Bayer-Schering, Merck, Teva and Novartis. YF has nothing to disclose. TK served on scientific advisory boards for BMS, Roche, Sanofi Genzyme, Novartis, Merck and Biogen, steering committee for Brain Atrophy Initiative by Sanofi Genzyme; received conference travel support and/or speaker honoraria from WebMD Global, Novartis, Biogen, Sanofi-Genzyme, Teva, BioCSL and Merck; and received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene and Merck.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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