Exercise and physical activity for fatigue, disease activity and immune-inflammatory outcomes in adults with systemic lupus erythematosus: an umbrella review.

Background: Fatigue and impaired health-related quality of life are common in systemic lupus erythematosus (SLE), and persistent immune-inflammatory activation may contribute to symptom burden even when clinical disease activity is controlled. Exercise and physical activity are recommended as non-pharmacological adjuncts, but existing systematic reviews overlap and report discordant conclusions. We undertook an umbrella review to synthesize evidence on clinical outcomes and to map immune-inflammatory outcomes. Methods: We searched PubMed, Embase, the Cochrane Library, Web of Science, Scopus and SPORTDiscus from inception to 1 March 2026 for systematic reviews, with or without meta-analysis, of exercise, physical activity, sedentary behavior or related lifestyle/self-management interventions in adults with SLE. Methodological quality was assessed with AMSTAR-2, overlap with the corrected covered area (CCA), and certainty with GRADE for intervention comparisons and the Ioannidis classification for observational associations. Because primary studies overlapped substantially, review estimates were not pooled; findings were synthesized narratively by construct and comparator, prioritizing Core-eligible reviews. Results: Eighteen reviews were included; seven were Core-eligible. AMSTAR-2 confidence was high in one review, low in five and critically low in twelve, and overall overlap was very high (CCA 19.6%). For fatigue versus usual care, two Core-eligible reviews reported statistically significant reductions (MD -0.61, 95% CI -1.19 to -0.02; 2 trials, 115 participants; and MD -0.52, 95% CI -0.91 to -0.13; 3 trials, 135 participants), whereas the high-confidence Cochrane review found no significant difference (MD -0.59, 95% CI -1.40 to 0.22; 2 trials, 104 participants); certainty was low, and all three estimates derived from an overlapping pool of four small primary trials. Disease-activity estimates were not statistically significant. Withdrawal comparisons were statistically inconclusive and of very low certainty; flare evidence was sparse and ungraded. Conclusions: Exercise and physical activity may slightly reduce fatigue in adults with SLE, but the evidence is low-certainty and substantially overlapping. Current review-level evidence does not establish a robust immune-inflammatory mechanism or a disease-activity effect, and safety and tolerability remain uncertain. Future trials should prespecify fatigue, disease activity, flares and immunological endpoints. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261392698, identifier CRD420261392698.