Proportion and characteristics of secondary progressive multiple sclerosis in five European registries using objective classifiers

Author:

Forsberg Lars1ORCID,Spelman Tim1,Klyve Pernilla1,Manouchehrinia Ali12ORCID,Ramanujam Ryan13ORCID,Mouresan Elena1,Drahota Jiri45ORCID,Horakova Dana5ORCID,Joensen Hanna6,Pontieri Luigi6ORCID,Magyari Melinda67,Ellenberger David8ORCID,Stahmann Alexander8ORCID,Rodgers Jeff9ORCID,Witts James9,Middleton Rod9,Nicholas Richard910ORCID,Bezlyak Vladimir11,Adlard Nicholas11,Hach Thomas11,Lines Carol11,Vukusic Sandra12ORCID,Soilu-Hänninen Merja13ORCID,van der Walt Anneke14ORCID,Butzkueven Helmut14,Iaffaldano Pietro15ORCID,Trojano Maria15,Glaser Anna1,Hillert Jan1ORCID,

Affiliation:

1. Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden

2. Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden

3. Department of Mathematics, Royal Institute of Technology, Stockholm, Sweden

4. Czech National Multiple Sclerosis ReMuS, IMPULS Endowment Fund, Prague, Czech Republic

5. First Faculty of Medicine and General University Hospital, Department of Neurology and Center of Clinical Neuroscience, Charles University in Prague, Prague, Czech Republic

6. The Danish Multiple Sclerosis Registry, Copenhagen University Hospital, Copenhagen, Denmark

7. Danish Multiple Sclerosis Center, Copenhagen University Hospital, Copenhagen, Denmark

8. MS Forschungs- und Projektentwicklungs-gGmbH, Hannover, Germany

9. Swansea University Medical School, Swansea, UK

10. Department of Cellular and Molecular Neuroscience, Imperial College London, London, UK

11. Novartis Pharma AG, Basel, Switzerland

12. Hôpital Neurologique, Service de Neurologie A, the European Database for Multiple Sclerosis (EDMUS), Coordinating Center and INSERM U 433, Lyon, France

13. Division of Clinical Neurosciences, University Hospital and University of Turku, Turku, Finland

14. Department of Neuroscience, Central Clinical School, Monash University, Melbourne, Australia

15. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Bari, Italy

Abstract

Background To assign a course of secondary progressive multiple sclerosis (MS) (SPMS) may be difficult and the proportion of persons with SPMS varies between reports. An objective method for disease course classification may give a better estimation of the relative proportions of relapsing–remitting MS (RRMS) and SPMS and may identify situations where SPMS is under reported. Materials and methods Data were obtained for 61,900 MS patients from MS registries in the Czech Republic, Denmark, Germany, Sweden, and the United Kingdom (UK), including date of birth, sex, SP conversion year, visits with an Expanded Disability Status Scale (EDSS) score, MS onset and diagnosis date, relapses, and disease-modifying treatment (DMT) use. We included RRMS or SPMS patients with at least one visit between January 2017 and December 2019 if ≥ 18 years of age. We applied three objective methods: A set of SPMS clinical trial inclusion criteria (“EXPAND criteria”) modified for a real-world evidence setting, a modified version of the MSBase algorithm, and a decision tree-based algorithm recently published. Results The clinically assigned proportion of SPMS varied from 8.7% (Czechia) to 34.3% (UK). Objective classifiers estimated the proportion of SPMS from 15.1% (Germany by the EXPAND criteria) to 58.0% (UK by the decision tree method). Due to different requirements of number of EDSS scores, classifiers varied in the proportion they were able to classify; from 18% (UK by the MSBase algorithm) to 100% (the decision tree algorithm for all registries). Objectively classified SPMS patients were older, converted to SPMS later, had higher EDSS at index date and higher EDSS at conversion. More objectively classified SPMS were on DMTs compared to the clinically assigned. Conclusion SPMS appears to be systematically underdiagnosed in MS registries. Reclassified patients were more commonly on DMTs.

Funder

Novartis

Publisher

SAGE Publications

Subject

Cellular and Molecular Neuroscience,Neurology (clinical)

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