The Efficacy of Antioxidative Stress Therapy on Oxidative Stress Levels in Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials

OBJECTIVE: To explore the efficacy of antioxidative stress therapy on oxidative stress levels in rheumatoid arthritis (RA) by a systematic review and meta-analysis of randomized controlled trials. METHODS: Chinese and English databases such as PubMed, Embase, China National Knowledge Infrastructure (CNKI), and China Biomedical Literature were searched, mainly searching for clinical randomized controlled trials of antioxidant therapy for rheumatoid arthritis. The search time is from the establishment of the database to July 2021. Two researchers independently carried out literature search, screening, and data extraction. The bias risk tool provided by the Cochrane Collaboration was used to evaluate the bias risk of all the included literature, and the RevMan 5.3 software was used for meta-analysis. RESULTS: A total of 24 RCTs (28 records) and 1277 participants were included. The time span of randomized controlled trials (RCTs) is from 1986 to 2020. These RCTs involve 14 types of antioxidants or antioxidant therapies, and these therapies have varying degrees of improvement on oxidative stress in RA patients. The summary results showed that the MDA in the experiment group is lower (SMD -0.82, 95% CI -1.35 to -0.28, P = 0.003). The difference of TAC, SOD, NO, GPx, CAT, and GSH between two groups was of no statistical significance (TAC (SMD 0.27, 95% CI -0.21 to 0.75, P = 0.27), SOD (SMD 0.12, 95% CI -0.16 to 0.40, P = 0.41), NO (SMD -2.03, 95% CI -4.22 to 0.16, P = 0.07), GPx (SMD 0.24, 95% CI -0.07 to 0.54, P = 0.13), CAT (SMD 2.95, 95% CI -2.6 to 8.51, P = 0.30), and GSH (SMD 2.46, 95% CI -0.06 to 4.98, P = 0.06)). For adverse events, the summary results showed that the difference was of no statistical significance (RR 1.16, 95% CI 0.79 to 1.71, P = 0.45). In addition, antioxidant therapy has also shown improvement in clinical efficacy indexes (number of tender joints, number of swollen joints, DAS28, VAS, and HAQ) and inflammation indexes (ESR, CRP, TNF-α, and IL6) for RA patients. CONCLUSION: The existing evidence shows potential benefits, mainly in reducing MDA and increasing TAC and GSH in some subgroups. However, more large samples and higher quality RCTs are needed to provide high-quality evidence, so as to provide more clinical reference information for the antioxidant treatment of RA.