Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep;8(5):665-678.
doi: 10.1007/s41669-024-00501-x. Epub 2024 Jul 1.

Cost and Quality of Life of Disability Progression in Multiple Sclerosis Beyond EDSS: Impact of Cognition, Fatigue, and Limb Impairment

Jürgen Wasem  1 , Yanic Heer  2 , Eleni Karamasioti  2 , Erwan Muros-Le Rouzic  3 , Giuseppe Marcelli  4 , Danilo Di Maio  4 , Stefan Braune  5 , Gisela Kobelt  6   7 , Paul Dillon  4
Affiliations

Cost and Quality of Life of Disability Progression in Multiple Sclerosis Beyond EDSS: Impact of Cognition, Fatigue, and Limb Impairment

Jürgen Wasem et al. Pharmacoecon Open. 2024 Sep.

Abstract

Background and objective: Understanding the socioeconomic burden of multiple sclerosis (MS) is essential to inform policymakers and payers. Real-world studies have associated increasing costs and worsening quality of life (QoL) with disability progression. This study aims to further evaluate the impact of cognition, fatigue, upper and lower limb function (ULF, LLF) impairments, and disease progression per Expanded Disability Status Scale (EDSS) level, on costs and QoL.

Methods: This was a cross-sectional cohort study including 20,988 patients from the German NeuroTransData MS registry from 2009 to 2019. QoL analyses were based on EQ-5D-5L. Cost analyses included indirect/direct medical and non-medical costs. Eight subgroups, ranging from 439 to 1812 patients were created based on presence of measures for disease progression (EDSS), cognition (Symbol Digit Modalities Test [SDMT]), fatigue (Modified Fatigue Impact 5-Item Scale [MFIS-5]), ULF (Nine-Hole Peg Test [9HPT]), and LLF (Timed 25-Foot Walk [T25FW]). Multivariable linear regression assessed the independent effect of each test's score on QoL and costs, while adjusting for EDSS and 12 other confounders.

Results: Lower QoL was associated with decreasing cognition (p < 0.001), worsening ULF (p = 0.025), and increasing fatigue (p < 0.0001); however, the negative impact of LLF worsening on QoL was not statistically significant (p = 0.54). Higher costs were associated with decreasing cognition (p < 0.001), worsening of ULF (p = 0.0058) and LLF (p = 0.049), and increasing fatigue (p < 0.0001). Each 1-scale-step worsening function of SDMT, MFIS-5, 9HPT, and T25FW scores resulted in €170, €790, €330, and €520 higher costs, respectively. Modeling disability progression based on SDMT, MFIS-5, 9HPT, and T25FW scores as an interaction with EDSS strata found associations with lower QoL and higher costs at variable EDSS ranges.

Conclusions: Disease progression in MS measured by 9HPT, SDMT, and MFIS-5 had a significant negative impact on QoL and broad socioeconomic costs independent of EDSS. T25FW had a significant negative association with costs. Cognition, fatigue, ULF, and LLF have stronger impact on costs and QoL in patients with higher EDSS scores. Additional determinants of MS disability status, including SDMT, MFIS-5, 9HPT, and T25FW, should be considered for assessing cost effectiveness of novel therapeutics for MS.

PubMed Disclaimer

Conflict of interest statement

Jürgen Wasem is Professor for Health Services Management at University Duisburg-Essen, Essen, Germany. He received an honorarium for consulting the study concept and quality assurance of data calculations. Yanic Heer was an employee of PricewaterhouseCoopers (PwC), Zurich, Switzerland during completion of the work related to this manuscript. Eleni Karamasioti was an employee of PricewaterhouseCoopers (PwC), Zurich, Switzerland during completion of the work related to this manuscript. Erwan Muros-Le Rouzic is an employee of and a shareholder in F. Hoffmann-La Roche Ltd., Basel, Switzerland. Giuseppe Marcelli is an employee of F. Hoffmann-La Roche Ltd., Basel, Switzerland. Danilo Di Maio is an employee of F. Hoffmann-La Roche Ltd., Basel, Switzerland. Stefan Braune received honoraria from Kassenärztliche Vereinigung Bayerns and health maintenance organizations for patient care; and from Biogen, Merck, NeuroTransData, Novartis, and Roche for consulting, project management, clinical studies, and lectures; he also received honoraria and expense compensation as a board member of NeuroTransData. Gisela Kobelt is President of EHE International GmbH and an employee of European Health Economics, Mulhouse, France. Paul Dillon was an employee of F. Hoffmann-La Roche Ltd., Basel, Switzerland during completion of the work related to this manuscript and has shares/ownership of F. Hoffmann-La Roche Ltd.

Figures

Fig. 1
Fig. 1
Study population overview flowcharts for a QoL/utility and b HCRU/costs. aSPMS patients (e.g., on interferon) are not excluded even though interferon does not have a label for SPMS. bFull covariate list: Age, sex, living status, educational attainment, time since diagnosis, time since manifestation, MS subtype, time since last relapse, number of relapses in previous year, time since last confirmed disability progression, current DMT, and time since last DMT change. 9HPT Nine-Hole Peg Test, DMT disease-modifying therapy, EDSS Expanded Disability Status Scale, EQ-5D-5L European Quality of Life 5-Dimensions Questionnaire-Five Levels, HCRU healthcare resource utilization, MFIS-5 Modified Fatigue Impact 5-Item Scale, MS multiple sclerosis, NTD NeuroTransData, QoL quality of life, SDMT Symbol Digit Modalities Test, SPMS secondary progressive multiple sclerosis, T25FW Timed 25-Foot Walk
Fig. 2
Fig. 2
Distributions of a SDMT, b MFIS-5, c 9HPT, and d T25FW scores for the QoL population, separated by EDSS strata. 9HPT Nine-Hole Peg Test, EDSS Expanded Disability Status Scale, MFIS-5 Modified Fatigue Impact 5-Item Scale, QoL quality of life, SDMT Symbol Digit Modalities Test, T25FW Timed 25-Foot Walk
Fig. 3
Fig. 3
Forest plots for a cognition (SDMT), b fatigue (MFIS-5), c upper limb (9HPT), and d lower limb function (T25FW) outcome measures to QoL/utility within strata of EDSS. 9HPT Nine-Hole Peg Test, CI confidence interval, EDSS Expanded Disability Status Scale, MFIS-5 Modified Fatigue Impact 5-Item Scale, QoL quality of life, SDMT Symbol Digit Modalities Test, T25FW Timed 25-Foot Walk
Fig. 4
Fig. 4
Distributions of a SDMT, b MFIS-5, c 9HPT, and d T25FW scores for the costs population, separated by EDSS strata. 9HPT Nine-Hole Peg Test, EDSS Expanded Disability Status Scale, MFIS-5 Modified Fatigue Impact 5-Item Scale, SDMT Symbol Digit Modalities Test, T25FW Timed 25-Foot Walk
Fig. 5
Fig. 5
Forest plots for a cognition (SDMT), b fatigue (MFIS-5), c upper limb (9HPT), and d lower limb function (T25FW) outcome measures to HCRU/costs within strata of EDSS. 9HPT Nine-Hole Peg Test, CI confidence interval, EDSS Expanded Disability Status Scale, HCRU healthcare resource utilization, MFIS-5 Modified Fatigue Impact 5-Item Scale, SDMT Symbol Digit Modalities Test, T25FW Timed 25-Foot Walk
See this image and copyright information in PMC

References

    1. Walton C, King R, Rechtman L, et al. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler. 2020;26(14):1816–21. 10.1177/1352458520970841. 10.1177/1352458520970841 - DOI - PMC - PubMed
    1. Dobson R, Giovannoni G. Multiple sclerosis—a review. Eur J Neurol. 2019;26(1):27–40. 10.1111/ene.13819. 10.1111/ene.13819 - DOI - PubMed
    1. Kappos L, Wolinsky JS, Giovannoni G, et al. Contribution of relapse-independent progression vs relapse-associated worsening to overall confirmed disability accumulation in typical relapsing multiple sclerosis in a pooled analysis of 2 randomized clinical trials. JAMA Neurol. 2020;77(9):1132–40. 10.1001/jamaneurol.2020.1568. 10.1001/jamaneurol.2020.1568 - DOI - PMC - PubMed
    1. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology. 1983;33:1444–52. 10.1212/wnl.33.11.1444. 10.1212/wnl.33.11.1444 - DOI - PubMed
    1. Lavery AM, Verhey LH, Waldman AT. Outcome measures in relapsing-remitting multiple sclerosis: capturing disability and disease progression in clinical trials. Mult Scler Int. 2014;2014: 262350. 10.1155/2014/262350. 10.1155/2014/262350 - DOI - PMC - PubMed

LinkOut - more resources