Fatigue prevalence, interactions with associated symptoms and longitudinal changes in those with multiple sclerosis: Insights from the TONiC study

AIMS: Fatigue is a pervasive feature of multiple sclerosis (MS) and its interaction with other MS symptoms is complex. These interactions were explored over time in a large cohort of adults with MS, using a measure reflecting a patient-based definition of MS fatigue. METHODS: Participants were recruited across the UK to complete a questionnaire pack, measuring fatigue and associated demographic, clinical and symptom factors, repeated serially over up to 54 months. Following conversion to interval-level estimates, data were analysed by regression, structural equation and trajectory modelling, and Classification and Regression Tree Analysis. RESULTS: In 6356 people with MS, the prevalence of moderate/severe fatigue was 565.4/1000 (95% CI: 553.0-577.8), with no difference between sexes but significantly higher in progressive subtypes. Peak prevalence was from age 50-64. Spasticity-related pain, physical/cognitive function, anxiety, visual problems and non-restorative sleep were associated with increased fatigue. Self-efficacy had strong influences to reduce fatigue. Use of disease modifying treatment was associated with worse fatigue. Trajectory analysis showed four groups, 28.9% have ongoing severe fatigue, 66.3% fall into two worsening fatigue groups with different inception points. Only 4.9% had low, stable fatigue. These four groups varied significantly by MS subtype, EDSS, symptoms, comorbidity, and employment. The risk of fatigue worsening to moderate/severe over the ensuing 27 months could be predicted by sex, EDSS, vision and self-efficacy. CONCLUSIONS: The factors interacting with MS fatigue need consideration when managing this prevalent symptom. In addition, their effect should be accounted for in any MS trial where fatigue is an outcome.