Application of definitions for conversion to secondary progressive MS in a Danish nationwide population

Tine Iskov Kopp,Stephan Bramow,Zsolt Illes,Matthias Kant,Claudia Kristensen,Peter Vestergaard Rasmussen,Finn Sellebjerg,Melinda Magyari

doi:10.1016/j.msard.2021.103319

Abstract

BackgroundThe number of patients with relapsing remitting multiple sclerosis (RRMS) who convert to secondary progressive (SP) MS is uncertain, and with emerging treatment options for SPMS, it is important to identify RRMS patients in transition to the SP phase. The objective of the present study was to characterize clinical parameters and use of disease modifying therapies in patients diagnosed with SPMS and RRMS patients already entered the SP phase by use of the Danish Multiple Sclerosis Registry (DMSR). MethodsWe used a cross-sectional design, including all living patients with MS as of June 30, 2020 from DMSR. First, we applied the MSBase definition of SPMS on all RRMS patients. Second, we applied the slightly modified inclusion criteria from the EXPAND clinical trial on patients with clinically confirmed SPMS and patients with RRMS fulfilling the MSBase definition of SPMS to identify SPMS patients recently progressed who may benefit from treatment with disease modifying therapy. We compared clinical characteristics and disease-modifying therapy use in the different patient groups. ResultsAmong patients with clinically confirmed SPMS, application of a slightly modified EXPAND trial inclusion criteria for SPMS (m-EXPAND) captured patients who had converted to SPMS more recently and who had relapsed and initiated high-efficacy treatment more frequently. Moreover, our RRMS patients fulfilling the “SPMS”-criteria according to MSBase and recently progression according to m-EXPAND had similar characteristics and remarkably resembled the SPMS population in the EXPAND trial. ConclusionOur results indicate that data-driven diagnostic definitions might help identify RRMS patients at risk for SPMS and we highlight the challenges and reluctance in diagnosing SPMS in clinical practice.

Highlights

Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal degeneration and is among the most common causes of neurological disability in young adults in the Western world (Reich et al, 2018)
Baseline demographic and clinical characteristics of the cohort at index date are presented as numbers with their percentages and medians with interquartile range (IQR)
Compared to clinically assigned secondary progressive MS (SPMS) patients, patients with MSBase SPMS were younger at onset (31 vs 34 years), diagnosis (36 vs 40 years), SPMS conversion (44 vs 50 years) and index date (52 vs 61), had shorter disease duration at time of SPMS conversion (10 vs 14 years), more relapses after SPMS conversion (52 vs 17%), were more often treated with disease-modifying therapy (DMT) (88 vs 32%) – especially high efficacy DMT (62 vs 18%), but the Expanded Disability Status Scale (EDSS) score was only 0.5 point lower at SPMS conver sion (EDSS 4.5 vs 5.0) and 1.0 point lower at index date (EDSS 5.0 vs 6.0)

Summary

Introduction

Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal degeneration and is among the most common causes of neurological disability in young adults in the Western world (Reich et al, 2018). In 2% - 5% of patients per annum and typically after 10 - 15 years, patients may convert to a secondary progressive MS (SPMS) disease course, characterised by gradually accumulating irreversible disability in ambulatory, autonomic and cognitive functions (Rovaris et al, 2006; Vukusic and Confavreux, 2003; Weinshenker et al, 1989). This phase is thought to be driven by chronic and CNS-compartmentalized inflam mation, slow rim-like plaque expansion and neuroaxonal degeneration (Bramow et al, 2010; Frischer et al, 2015, 2009). Conclusion: Our results indicate that data-driven diagnostic definitions might help identify RRMS patients at risk for SPMS and we highlight the challenges and reluctance in diagnosing SPMS in clinical practice

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Conclusion