Non-pharmacological interventions in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

PURPOSE: To investigate the role of non-pharmaceutical therapies on disease activity in rheumatoid arthritis through systematic review and meta-analysis. METHODS: A review of Pubmed, EMBASE, Web of Science, and the Cochrane Library was performed from inception until March 26, 2019. Only randomized controlled trials which assessed oral, non-pharmacological interventions (e.g. diets, vitamins, oils, herbal remedies, fatty acids, supplements, etc.) in adult patients with rheumatoid arthritis, that presented clinically-relevant outcomes (defined as pain, fatigue, disability, joint counts, and/or disease indices) were included in our meta-analysis. Data were analyzed as mean differences between active and placebo and forest plots were performed. Heterogeneity was evaluated using I-squared statistics while funnel plots and Cochrane's risk of bias assessment evaluated bias. RESULTS: 8170 articles were identified in the search and 51 were RCTs were included. The mean difference in DAS28 was significantly improved in experimental group treated with diet (-0.46 [-0.91, -0.02], p = 0.04), zinc sulfate, copper sulphate, selenium, potassium, lipoic acid, turmeric, pomegranate extract, chamomile, and cranberry extract supplements (-0.77 [-1.17, -0.38], p < 0.001), A, B6, C, D, E, and K vitamins (-0.52 [-0.74, -0.29], p < 0.001), and fatty acids (-0.19 [-0.36, -0.01], p = 0.03). Other clinical metrics such as SJC, TJC, HAQ, SDAI, ACR20, and self-reported pain were decreased in the treatment groups. There was significant reporting bias in the studies. CONCLUSION: Some non-pharmacological therapies may modestly improve some clinical outcomes in patients with rheumatoid arthritis. Many identified studies lacked full reporting. Further clinical trials that are well-designed, adequately powered, and sufficiently report ACR improvement criteria or EULAR response criteria outcomes are needed to confirm the efficacy of these therapies.