Fatigue predicts disease worsening in relapsing-remitting multiple sclerosis patients

Background: It is unclear whether fatigue is a consequence or a predictive trait of disease worsening. Objective: To investigate the predictive value of fatigue toward conversion to confirmed moderate-severe disability in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: We retrospectively selected from the Comprehensive Longitudinal Investigations in MS at the Brigham and Women's Hospital (CLIMB) study cohort RRMS patients who converted to confirmed (2years) Expanded Disability Status Scale (EDSS) score 3 within a follow-up period 3years. We contrasted the Modified Fatigue Impact Scale (MFIS) score of 33 converters, obtained at least 1year before conversion to EDSS 3, with that of 33 non-converter RRMS patients matched for baseline characteristics. Results: Total MFIS score was higher in converter versus non-converter MS patients (median 37 vs 13; p<0.0001). EDSS and Center for Epidemiological Studies Depression scale (CES-D) scores were also higher in the converters (median EDSS 1.5 vs 0, p<0.0001; median CES-D 30 vs 24, p<0.0001) and were both associated with MFIS score (EDSS: rho=0.42, p=0.0005; CES-D: rho=0.72, p<0.0001). After adjusting for EDSS and CES-D in multivariate analysis, MFIS remained a significant predictor of subsequent conversion to confirmed EDSS 3. Conclusion: Fatigue is a promising indicator of risk for conversion to confirmed moderate-severe disability in RRMS patients.