. 2025 Jun;32(6):e70230.

doi: 10.1111/ene.70230.

Confirmed Worsening of Health-Related Quality of Life to Monitor Long-Term MS Disease Progression: A Longitudinal Analysis From the Swiss Multiple Sclerosis Registry

Stefania Iaquinto¹, Benjamin Victor Ineichen², Mina Stanikić^{1

3}, Jens Kuhle^{4

5}, Christian Philipp Kamm^{6

7}, Pasquale Calabrese⁸, Patrick Roth⁹, Claudia Baum¹⁰, Chiara Zecca^{11

12}, Claudio Gobbi^{11

12}, Özgür Yaldizli^{5

13}, Milo Alan Puhan¹, Viktor von Wyl^{1

3}; Swiss Multiple Sclerosis Registry

Collaborators, Affiliations

Collaborators

Affiliations

¹ Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
² Department of Clinical Research, University of Bern, Bern, Switzerland.
³ Institute for Implementation Science in Health Care, University of Zurich, Zurich, Switzerland.
⁴ Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Neurology Clinic and Policlinic, Department of Head, Spine and Neuromedicine, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
⁶ Department of Neurology, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
⁷ Neurology and Neurorehabilitation Center, Lucerne Cantonal Hospital, Lucerne, Switzerland.
⁸ Neuropsychology and Behavioral Neurology Unit, Division of Cognitive and Molecular Neuroscience, University of Basel, Basel, Switzerland.
⁹ Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
¹⁰ Rehabilitation Clinic Zihlschlacht, Zihlschlacht, Switzerland.
¹¹ Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.
¹² Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
¹³ Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.

PMID: 40468538
PMCID: PMC12137183
DOI: 10.1111/ene.70230

Confirmed Worsening of Health-Related Quality of Life to Monitor Long-Term MS Disease Progression: A Longitudinal Analysis From the Swiss Multiple Sclerosis Registry

Stefania Iaquinto et al. Eur J Neurol. 2025 Jun.

. 2025 Jun;32(6):e70230.

doi: 10.1111/ene.70230.

Authors

Collaborators

Affiliations

¹ Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland.
² Department of Clinical Research, University of Bern, Bern, Switzerland.
³ Institute for Implementation Science in Health Care, University of Zurich, Zurich, Switzerland.
⁴ Department of Neurology, University Hospital Basel and University of Basel, Basel, Switzerland.
⁵ Neurology Clinic and Policlinic, Department of Head, Spine and Neuromedicine, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Clinical Research and Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.
⁶ Department of Neurology, Inselspital, University Hospital Bern and University of Bern, Bern, Switzerland.
⁷ Neurology and Neurorehabilitation Center, Lucerne Cantonal Hospital, Lucerne, Switzerland.
⁸ Neuropsychology and Behavioral Neurology Unit, Division of Cognitive and Molecular Neuroscience, University of Basel, Basel, Switzerland.
⁹ Department of Neurology, University Hospital Zurich, Zurich, Switzerland.
¹⁰ Rehabilitation Clinic Zihlschlacht, Zihlschlacht, Switzerland.
¹¹ Department of Neurology, Neurocenter of Southern Switzerland, Ospedale Regionale di Lugano, EOC, Lugano, Switzerland.
¹² Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.
¹³ Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland.

PMID: 40468538
PMCID: PMC12137183
DOI: 10.1111/ene.70230

Abstract

Background: Monitoring multiple sclerosis (MS) progression traditionally relies on clinical measures, which may overlook symptoms affecting quality of life. Incorporating patient-reported outcomes could improve the understanding of disease worsening.

Objective: To evaluate an EQ-5D-based algorithm for detecting disease worsening and compare it with EDSS worsening.

Methods: We analyzed longitudinal EQ-5D and EDSS data from the Swiss MS Registry. EQ-5D worsening was defined as a sustained decline over two assessments; EDSS worsening followed established clinical criteria. Time to confirmed worsening was assessed using Kaplan-Meier curves and Cox regression. Patterns in 12 self-reported symptoms were examined using descriptive statistics and logistic regression.

Results: By year four, 4.5% experienced EQ-5D worsening, while 15.8% experienced EDSS worsening. Faster time to EQ-5D worsening was associated with walking aids or higher BMI at baseline. Conversely, faster time to EDSS worsening was associated with male sex, progressive MS, or spasms as the first symptom. Symptom frequency was higher in the EQ-5D worsening group, with pain and depression independently associated, while no symptoms were associated with EDSS worsening.

Discussion: While EQ-5D worsening does not serve as an early clinical marker of disease progression, it may complement EDSS by capturing additional aspects of disease progression, particularly symptoms impacting HRQoL, that are not reflected in EDSS progression. Long-term HRQoL monitoring alongside traditional measures may improve MS progression assessment and patient-centered care.

Keywords: EQ‐5D; disease progression; health‐related quality of life; multiple sclerosis; outcome measurement.

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Conflict of interest statement

Stefania Iaquinto, Benjamin Victor Ineichen, Mina Stanikić, Christian Philipp Kamm, Pasquale Calabrese, Claudia Baum, Milo Alan Puhan, Viktor von Wyl report no disclosures relevant to this manuscript. Jens Kuhle received speaker fees, research support, travel support, and/or served on advisory boards by Swiss MS Society, Swiss National Research Foundation (320030_212534/1), University of Basel, Progressive MS Alliance, Alnylam, Bayer, Biogen, Bristol Myers Squibb, Celgene, Immunic, Merck, Neurogenesis, Novartis, Octave Bioscience, Quanterix, Roche, Sanofi, Stata DX. Patrick Roth has received honoraria for lectures or advisory board participation from Alexion, Bristol‐Myers Squibb, Boehringer Ingelheim, Debiopharm, Galapagos, Merck Sharp and Dohme, Laminar, Midatech Pharma, Novocure, QED, Roche, Sanofi and Servier and research support from Merck Sharp and Dohme and TME Pharma. Chiara Zecca Ente Ospedaliero Cantonale (employer) received compensation for Chiara Zecca's speaking activities, consulting fees, or grants from Abbvie, Alexion, Almirall, Biogen, Bristol Meyer Squibb, Eisai, Lilly, Lundbeck, Merck, Merz, Novartis, Organon, Pfizer, Sandoz, Sanofi, Teva Pharma, Roche. Chiara Zecca is recipient of a grant for senior reseachers provided by AFRI (Area Formazione accademica, Ricerca e Innovazione), EOC. Claudio Gobbi Ente Ospedaliero Cantonale (employer) received compensation for Claudio Gobbi's speaking activities, consulting fees, or grants from Abbvie, Almirall, Biogen, Bristol Meyer Squibb, Lundbeck, Merck, Novartis, Sandoz, Sanofi, Teva Pharma, and Roche. Özgür Yaldizli received grants from ECTRIMS/MAGNIMS, University of Basel, Pro Patient Stiftung, University Hospital Basel, Free Academic Society Basel, Swiss National Science Foundation and the Swiss Multiple Sclerosis Society and advisory board fees from Biogen.

Figures

**FIGURE 1**
Flowchart of the study population. EDSS, Expanded Disability Status Scale; EQ‐5D, EuroQol‐5 Dimension; SMSR, Swiss Multiple Sclerosis Registry.

**FIGURE 2**
Kaplan–Meier curve of time to specific worsening events. EDSS, Expanded Disability Status Scale; EQ‐5D, EuroQol‐5 Dimension.

**FIGURE 3**
Radar plots of burden of specific MS symptoms. Symptom frequency (Panel A) or report of new symptom since baseline (Panel B), both assessed at the time of last available assessment in persons without EQ‐5D worsening (blue, n = 812) or at the time of EQ‐5D (maroon; n = 50) or EDSS worsening (green; n = 24).

See this image and copyright information in PMC

References

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Confirmed Worsening of Health-Related Quality of Life to Monitor Long-Term MS Disease Progression: A Longitudinal Analysis From the Swiss Multiple Sclerosis Registry

Collaborators

Affiliations

Confirmed Worsening of Health-Related Quality of Life to Monitor Long-Term MS Disease Progression: A Longitudinal Analysis From the Swiss Multiple Sclerosis Registry

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical