Effectiveness and safety of bee venom pharmacopuncture for rheumatoid arthritis-related pain and disease activity: a systematic review and meta-analysis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint pain, inflammation, and progressive joint destruction. Bee venom (BV) pharmacopuncture has been used in East Asia for RA, but its clinical effectiveness and safety remains uncertain. We evaluated BV pharmacopuncture for pain, disease activity, treatment response, and adverse events (AEs) in patients with RA.MethodsWe systematically searched PubMed, the Cochrane Library, Embase, SciELO, CNKI, CiNii, KISS, and other regional databases for randomized controlled trials (RCTs). Risk of bias was assessed using RoB 2, meta-analyses were conducted using RevMan 5.4, and the certainty of evidence was evaluated using GRADE.ResultsSeventeen RCTs involving 1,304 patients with RA were included, and 14 contributed to meta-analysis. Compared with Western medicine, BV significantly improved pain-related outcomes as monotherapy (standardized mean difference [SMD] −0.99, 95% confidence interval [CI] −1.37 to −0.60; I2 = 20%) and add-on therapy (SMD −1.14, 95% CI −2.11 to −0.17; I2 = 93%). Only one study evaluated disease activity using the Disease Activity Score in 28 joints based on the erythrocyte sedimentation rate and reported a significant benefit with BV. Although most other disease activity–related outcomes favored BV, the overall effect remained uncertain because the evidence was limited and heterogeneous. BV improved the response rate, defined as a ≥ 30% improvement, as add-on therapy (risk ratio [RR] 1.18, 95% CI 1.03 to 1.36; I2 = 9%), but not in direct comparisons with Western medicine (RR 1.07, 95% CI 1.00 to 1.16; I2 = 0%; p = 0.06). The risk of AEs was relatively low with BV monotherapy (risk difference [RD] −0.17, 95% CI −0.34 to −0.01; I2 = 37%) and add-on comparisons (RD = −0.16, 95% CI −0.26 to −0.06; I2 = 0%). No serious BV-related AEs, including anaphylaxis, were reported.ConclusionsBV pharmacopuncture may improve pain and treatment response in RA without increasing the risk of AEs. However, these findings are supported by low certainty of evidence, and the effect on disease activity remains uncertain. Further high-quality RCTs with standardized treatment protocols and validated outcome measures are warranted to establish its clinical efficacy and safety.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42021238058, PROSPERO CRD42021238058.