Efficacy of non-pharmacological interventions: a systematic review informing the 2023 EULAR recommendations for the management of fatigue in people with inflammatory rheumatic and musculoskeletal diseases

Objective: To identify the best evidence on the efficacy of non-pharmacological interventions in reducing fatigue in people with inflammatory rheumatic and musculoskeletal diseases (I-RMDs) and to summarise their safety in the identified studies to inform European Alliance of Associations for Rheumatology recommendations for the management of fatigue in people with I-RMDs. Methods: Systematic review of randomised controlled trials (RCTs) including adults with I-RMDs conducted according to the Cochrane Handbook. Search strategy ran in Medline, Embase, Cochrane Library, CINAHL Complete, PEDro, OTseeker and PsycINFO. Assessment of risk of bias, data extraction and synthesis were performed by two reviewers independently. Data were pooled in meta-analyses. Results: From a total of 4150 records, 454 were selected for full-text review, 82 fulfilled the inclusion criteria and 55 RCTs were included in meta-analyses. Physical activity or exercise was efficacious in reducing fatigue in rheumatoid arthritis (RA) (standardised mean differences (SMD)=−0.23, 95% CI=−0.37 to −0.1), systemic lupus erythematosus (SLE) (SMD=−0.54, 95% CI=−1.07 to −0.01) and spondyloarthritis (SMD=−0.94, 95% CI=−1.23 to −0.66); reduction of fatigue was not significant in Sjögren’s syndrome (SMD=−0.83, 95% CI=−2.13 to 0.47) and systemic sclerosis (SMD=−0.66, 95% CI=−1.33 to 0.02). Psychoeducational interventions were efficacious in reducing fatigue in RA (SMD=−0.32, 95% CI=−0.48 to −0.16), but not in SLE (SMD=−0.19, 95% CI=−0.46 to 0.09). Follow-up models in consultations (SMD=−0.05, 95% CI=−0.29 to 0.20) and multicomponent interventions (SMD=−0.20, 95% CI=−0.53 to 0.14) did not show significant reductions of fatigue in RA. The results of RCTs not included in the meta-analysis suggest that several other non-pharmacological interventions may provide a reduction of fatigue, with reassuring safety results. Conclusions: Physica activity or exercise and psychoeducational interventions are efficacious and safe for managing fatigue in people with I-RMDs