Efficacy and safety of tripterygium glycosides for Graves ophthalmopathy: A systematic review and meta-analysis

BACKGROUND: Graves ophthalmopathy (GO) is one of the remaining enigmas in thyroidology. Glucocorticoids (GCs) are strongly recommended but their effects are not completely satisfactory and adverse reactions can occur. Tripterygium glycosides (TG) is a promising component extracted from Tripterygium wilfordii Hook F (TwHF), and numerous patients with GO have benefited from it. However, its practical application value is still unclear. The aim of this systematic review and meta-analysis was to investigate the efficacy and safety of TG for patients with GO. METHODS: By retrieving the PubMed, Embase, the Cochrane Library, CNKI, VIP, CBM, and WanFang Databases, the open published randomized controlled trials (RCTs) related to TG in the treatment of GO were collected. And inclusion and exclusion criteria were established. The Cochrane bias risk assessment tool conducts the evaluation of included studies, and meta-analysis was performed using Revman 5.3 software. TRIAL REGISTRATION NUMBER: PROSPERO CRD42019131915. RESULTS: A total of 19 trials (involving 1517 GO patients) were included in this review with generally acceptable validity of included RCTs. TG therapy brought about a significantly higher efficacy rate compared with non-TG treatments (RR: 1.40; 95% CI: 1.31–1.49). Subgroup meta-analysis showed that TG with or without immunosuppressive therapies were all better than controls: with GC (RR: 1.36; 95% CI: 1.27–1.46), with multiple intensification of immunosuppressive therapies (RR: 1.91; 95% CI: 1.37–2.67), with no immunosuppressive therapies (RR: 1.39; 95% CI:1.21–1.59); the dosage of TG for 15–60 mg/d (RR: 1.41; 95% CI: 1.30–1.53) were better compared with for ≥90 mg/d (RR: 1.47; 95% CI: 1.29–1.68); the course of treatment for ≤3 months (RR: 1.43; 95% CI: 1.33–1.52) was better than controls, but when >3 months (RR: 1.15; 95% CI: 0.94–1.41) there was no significant differences. After treatment, the degree of exophthalmus (SMD: −2.55; 95% CI: −2.93 to 2.17), the recurrence rate of 1 year (RR: 0.45; 95% CI: 0.27–0.74), and adverse reactions rate (RR: 0.32; 95% CI: 0.20–0.53) were all lower, while the CAS was no obvious gap in 2 groups (SMD: 0.08; 95% CI: −0.60 to 0.75). CONCLUSIONS: This review found that TG has some advantages in treating GO, especially in improving clinical efficacy and reducing adverse reactions. Nevertheless, large sample, multi-center, reasonable design, and high quality clinical studies are still needed for further verification.