Multiple Sclerosis Severity Score (MSSS) improves the accuracy of individualized prediction in MS

Author:

Kalincik Tomas1ORCID,Kister Ilya2ORCID,Bacon Tamar E2,Malpas Charles B1,Sharmin Sifat1,Horakova Dana3ORCID,Kubala-Havrdova Eva3,Patti Francesco4ORCID,Izquierdo Guillermo5,Eichau Sara5ORCID,Ozakbas Serkan6,Onofrj Marco7,Lugaresi Alessandra8ORCID,Prat Alexandre9,Girard Marc9,Duquette Pierre9,Grammond Pierre10,Sola Patrizia11,Ferraro Diana12,Alroughani Raed13ORCID,Terzi Murat14,Boz Cavit15,Grand’Maison Francois16,Bergamaschi Roberto17,Gerlach Oliver18,Sa Maria J19,Kappos Ludwig20ORCID,Cartechini Elisabetta21,Lechner-Scott Jeannette22ORCID,van Pesch Vincent23,Shaygannejad Vahid24ORCID,Granella Franco25,Spitaleri Daniele26,Iuliano Gerardo27,Maimone Davide28,Prevost Julie29,Soysal Aysun30,Turkoglu Recai31,Ampapa Radek32,Butzkueven Helmut33,Cutter Gary34,

Affiliation:

1. CORe, Department of Medicine, The University of Melbourne, Melbourne, VIC, Australia/MS Centre, Department of Neurology, The Royal Melbourne Hospital, Melbourne, VIC, Australia

2. Neurology, NYU School of Medicine, New York, NY, USA

3. Department of Neurology, Charles University in Prague, Prague, Czech Republic

4. GF Ingrassia Department, University of Catania, Catania, Italy

5. Hospital Universitario Virgen Macarena, Sevilla, Spain

6. Dokuz Eylul University, Izmir, Turkey

7. Department of Neuroscience, Imaging, and Clinical Sciences, University G. d’Annunzio, Chieti, Italy

8. IRCCS Istituto delle Scienze Neurologiche di Bologna, Bologna, Italy/Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy

9. Universite de Montreal and CHUM, Montreal, QC, Canada

10. CISSS Chaudi’re-Appalache, Levis, QC, Canada

11. Neurology Unit, Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy

12. Neurology Unit, Department of Neuroscience, Azienda Ospedaliera Universitaria, Modena, Italy/Department of Biomedical, Metabolic and Neurosciences, University of Modena and Reggio Emilia, Modena, Italy

13. Division of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait

14. Medical Faculty, 19 Mayis University, Samsun, Turkey

15. KTU Medical Faculty Farabi Hospital, Trabzon, Turkey

16. Neuro Rive-Sud, Greenfield Park, QC, Canada

17. IRCCS Mondino Foundation, Pavia, Italy

18. Department of Neurology, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands/School for Mental Health and Neuroscience, Department of Neurology, Maastricht University Medical Centre, Maastricht, The Netherlands

19. Hospital S. João, Porto, Portugal; University Fernando Pessoa, Porto, Portugal

20. Research Center for Clinical Neuroimmunology and Neuroscience(RC2NB) and MS Center, Departments of Head, Spine and Neuromedicine, Clinical Research and Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland

21. UOC Neurologia, Azienda Sanitaria Unica Regionale Marche—AV3, Macerata, Italy

22. School of Medicine and Public Health, The University of Newcastle, Newcastle, NSW, Australia

23. Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, Belgium

24. Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran

25. Department of Medicine and Surgery, University of Parma, Parma, Italy

26. Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy

27. Ospedali Riuniti di Salerno, Salerno, Italy

28. Neurology Unit, Piazza S. Maria di Gesù 5, Catania, Italy

29. CSSS Saint-Jérôme, Saint-Jerome, QC, Canada

30. Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey

31. Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey

32. Nemocnice Jihlava, Jihlava, Czech Republic

33. Central Clinical School, Monash University, Melbourne, VIC, Australia

34. Department of Biostatistics, UAB School of Public Health, Birmingham, AL, USA

Abstract

Background: The MSBase prediction model of treatment response leverages multiple demographic and clinical characteristics to estimate hazards of relapses, confirmed disability accumulation (CDA), and confirmed disability improvement (CDI). The model did not include Multiple Sclerosis Severity Score (MSSS), a disease duration-adjusted ranked score of disability. Objective: To incorporate MSSS into the MSBase prediction model and compare model accuracy with and without MSSS. Methods: The associations between MSSS and relapse, CDA, and CDI were evaluated with marginal proportional hazards models adjusted for three principal components representative of patients’ demographic and clinical characteristics. The model fit with and without MSSS was assessed with penalized r2 and Harrell C. Results: A total of 5866 MS patients were started on disease-modifying therapy during prospective follow-up (age 38.4 ± 10.6 years; 72% female; disease duration 8.5 ± 7.7 years). Including MSSS into the model improved the accuracy of individual prediction of relapses by 31%, of CDA by 23%, and of CDI by 24% (Harrell C) and increased the amount of variance explained for relapses by 49%, for CDI by 11%, and for CDA by 10% as compared with the original model. Conclusion: Addition of a single, readily available metric, MSSS, to the comprehensive MSBase prediction model considerably improved the individual accuracy of prognostics in MS.

Funder

National Health and Medical Research Council

Genentech

Publisher

SAGE Publications

Subject

Neurology (clinical),Neurology

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