Effects and Safety of the Tripterygium Glycoside Adjuvant Methotrexate Therapy in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

Abstract

Objective. This study aimed to systematically review the efficacy and clinical safety of different courses and doses of tripterygium glycoside (TG) adjuvant methotrexate (MTX) therapy in the treatment of rheumatoid arthritis (RA). Methods. Randomized controlled trials (RCTs) of TG adjuvant MTX therapy in patients with RA were retrieved from SinoMed, China Network Knowledge Infrastructure, WanFang Data, PubMed, Cochrane Library, and Embase from inception to September 30, 2021. The effects and clinical safety evaluations were conducted using RevMan 5.3 software. Results. A total of 9 RCTs and 892 patients with RA were included in this study. In the meta-analysis, a total of 463 and 429 patients were enrolled into the TG adjuvant MTX therapy group and MTX monotherapy group, respectively. In comparison with MTX monotherapy, the results of the analyzed effects showed that the TG adjuvant MTX therapy can achieve 20%, 50%, and 70% improvements in American College of Rheumatology (ACR) criteria ACR20, ACR50, and ACR70 at $P$  = 0.005, $P$  = 0.0001, and $P$  = 0.004, respectively. Simultaneously, the efficacy of the TG adjuvant MTX therapy was improved at either 30 or 60 mg/day over a six-month course compared to MTX monotherapy ( $P$  < 0.0001). There was no statistical difference in the effects between the doses of 30 and 60 mg/day after three months ( $P$  = 0.82). TG adjuvant MTX also reduced the expression rate of the swollen joint count, tender joint count, erythrocyte sedimentation rate, rheumatoid factor, and C-reactive protein in subgroup analyses with different courses and doses. In terms of hepatic adverse effects ( $P$  = 0.28), leukopenia ( $P$  = 0.78), gastrointestinal adverse effects ( $P$  = 0.17), cutaneous adverse effects ( $P$  = 0.94), and irregular menstruation adverse effects ( $P$  = 0.29), there was no statistically significant difference with TG adjuvant MTX therapy and MTX monotherapy with different courses and doses. Conclusions. TG adjuvant MTX therapy is more effective than MTX monotherapy and is a safe strategy for RA treatment in doses of 30 or 60 mg/day over a treatment course of six months. However, high-quality multicenter RCT studies with large sample sizes are still needed to confirm the effects and clinical safety of different courses and doses of TG adjuvant MTX therapy.