Tripterygium Glycoside Tablets Combined With Conventional Synthetic Disease-Modifying Antirheumatic Drugs for Treating Rheumatoid Arthritis: Protocol for a Prospective, Multicenter, Open-Label Randomized Controlled Trial.

Background: Tripterygium glycoside tablets (TGTs), a traditional Chinese medicine-based therapy and a type of conventional synthetic disease-modifying antirheumatic drug (csDMARD), have shown promise as a cost-effective alternative for rheumatoid arthritis (RA). However, there is limited evidence regarding the most effective combinations with other csDMARDs, such as methotrexate, leflunomide, and hydroxychloroquine. This study evaluates the 12-week efficacy and safety of TGT-based regimens in patients with moderately active RA. Objective: This study aims to evaluate the clinical efficacy and safety of the csDMARD combination regimens mainly based on TGTs in the treatment of RA, using multicenter clinical data, and to explore the clinical characteristics of TGTs and identify the optimal combination therapy through a randomized controlled trial. Methods: This multicenter, open-label randomized controlled trial recruited 188 participants (47 per group) from 3 hospitals. Eligible patients were stratified by study center and randomized in a 1:1:1:1 ratio to receive TGT monotherapy, TGT plus methotrexate, TGT plus leflunomide, or TGT plus hydroxychloroquine. The primary outcome was the American College of Rheumatology 20% improvement response rate. Secondary outcome measures included the Disease Activity Score-28 (DAS28) using erythrocyte sedimentation rate and DAS28 using C-reactive protein response rates, the Clinical Disease Activity Index, the Simplified Disease Activity Index, the pain visual analog scale (0 to 10 points), the patient global assessment, the medical doctor global assessment, quality of life (36-Item Short Form Health Survey), and the Health Assessment Questionnaire Disability Index. All enrolled patients were followed up every 4 weeks for a total of 12 weeks. Adverse events were recorded during the observation period of the study. All patients randomized in this study will be included in the intention-to-treat analysis. Results: This study was funded in February 2024. Funding was provided by the Beijing Tongzhou District Science and Technology Planning Project. Recruitment of participants commenced on September 1, 2024, and concluded on December 31, 2025. A total of 181 patients were enrolled. Final data collection has been completed, and data cleaning is currently underway. Statistical analyses have not yet been performed. The primary results are expected to be submitted for publication by the end of 2026. Conclusions: This trial uses multicenter clinical data to provide robust evidence on the efficacy and safety of TGTs in combination with csDMARDs for the treatment of RA with moderate disease activity.