Relapses add to permanent disability in relapsing multiple sclerosis patients

Nils Koch-Henriksen,Per Soelberg Sørensen,Melinda Magyari

doi:10.1016/j.msard.2021.103029

Abstract

ObjectiveWhether relapses have direct effects on permanent disability in multiple sclerosis is still an unsettled issue. We aimed at investigating the cumulative effect of breakthrough relapses on the Expanded Disability Status Scale (EDSS) in relapsing-onset MS patients under disease modifying therapy (DMT). MethodsFrom the Danish Multiple Sclerosis Registry we identified all patients in Denmark with relapsing-onset MS who had started DMT and followed them from the first day of treatment. We included patients aged 18-59 with Kurtzke's EDSS score < 6.0 at entry, and we compared patients with and without relapses during follow-up. Endpoints were 1) annualized increase in EDSS; 2) time to 6-month sustained EDSS-worsening; 3) time to EDSS 6.0; and 4) time to increase in pyramidal- and cerebellar functional systems. Patients with and without relapses after entry were 1:1 matched by sex, EDSS, and age at entry. We analysed EDSS-worsening with adjusted Generalized Linear Models and time to the endpoints with adjusted Cox regression. ResultsWe included 1,428 patients with breakthrough relapses and 1,428 without. The adjusted annualized increase in EDSS was 0.179 in patients with relapses (95% CI 0.164 – 9.194) and 0.086 in patients without relapses (95% CI 0.074 – 0.097), but in patients with EDSS ≥ 4.0 at entry there was no difference. The hazard ratio for irreversible worsening of EDSS was 1.83 (95% CI 1.58 – 2.12) and for irreversible increase to EDSS 6.0 or more 1.62 (95% CI 1.25 – 2.10). Irreversible increase in pyramidal and cerebellar functional system scores also happened significantly earlier in patients with breakthrough relapses. ConclusionsOur results indicate that breakthrough relapses under DMT is associated with increasing permanent disability in patients with EDSS < 4.0 at treatment start which calls for effective prevention of relapses.

Highlights

After decades of using disease modifying treatments (DMTs) in pa tients with relapsing remitting multiple sclerosis (RRMS) there is still some disagreement about the effects of relapses on long-term disability
The predictive value of early relapses for transition to the secondary progressive phase or reach of specific milestones of the Expanded Disability Status Scale (EDSS) score (Kurtzke, 1983) have been exam ined in many studies with conflicting results ranging from no predictive value of relapses (Casserly and Ebers, 2011; Confavreux et al, 2000) to predictive value of relapses and EDSS worsening in the first few years after onset (Scalfari et al, 2013, 2010) or after start of disease modifying therapy (DMT) (Rio et al, 2018)
At each scheduled visit, the physician clini cally examined and scored the patients according to the EDSS and Functional Systems Score (FS) (Kurtzke, 1983) and decided whether new symptoms reported by the patient represented true relapses

Summary

Introduction

After decades of using disease modifying treatments (DMTs) in pa tients with relapsing remitting multiple sclerosis (RRMS) there is still some disagreement about the effects of relapses on long-term disability. The predictive value of early relapses for transition to the secondary progressive phase or reach of specific milestones of the Expanded Disability Status Scale (EDSS) score (Kurtzke, 1983) have been exam ined in many studies with conflicting results ranging from no predictive value of relapses (Casserly and Ebers, 2011; Confavreux et al, 2000) to predictive value of relapses and EDSS worsening in the first few years after onset (Scalfari et al, 2013, 2010) or after start of DMT (Rio et al, 2018). The particular view that MS in all cases is a primarily progressive disease with or without superimposed relapses, not adding to disability, is currently being discussed

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