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

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.