Physical and mental health-related quality of life outcomes of non-pharmacological interventions in early multiple sclerosis: A systematic review and meta-analysis

Objective To determine the effect of non-pharmacological interventions on physical and mental health-related quality of life among adults with early diagnosed multiple sclerosis. Data sources PubMed, EMBASE, Cochrane CENTRAL, ClinicalTrials.gov and APA PsycINFO were searched from database inception to 8 July 2026. Review methods We conducted a systematic review and meta-analysis of randomised controlled trials comparing non-pharmacological interventions with control conditions in adults with early-stage multiple sclerosis and minimal disability. Outcomes were physical and mental health-related quality of life after treatment and at follow-up. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Effects were pooled using standardised mean differences. Results Eleven randomised controlled trials including 696 participants were included. The updated search identified no additional eligible trials. Interventions included exercise, physiotherapy, balance training, cognitive rehabilitation and behavioural therapies. After treatment, interventions produced a small improvement in physical health-related quality of life, with a standardised mean difference of 0.28 and a 95% confidence interval from 0.11 to 0.46. The effect on mental health-related quality of life was smaller and uncertain, with a standardised mean difference of 0.16 and a 95% confidence interval from −0.04 to 0.35. Follow-up effects were not clearly sustained. Conclusion Non-pharmacological interventions may provide modest short-term physical health-related quality-of-life benefits. Effects on mental health-related quality of life and digitally delivered rehabilitation remain uncertain.