Efficacy,safety, and cost-effectiveness of triple therapy in preventing relapse in rheumatoid arthritis: A randomized controlled trial (ESCoRT study)

Background:Biological agents, such as tumor necrosis factor inhibitors (TNFi), have been widely used in rheumatoid arthritis (RA) patients and greatly improved goal achievement. The aim of this study was to investigate whether conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) combination was better in reducing relapse than methotrexate (MTX) monotherapy, and more cost-effective than continuing TNFi plus MTX in RA patients who achieved low disease activity (LDA) with TNFi and MTX therapy.Methods:RA patients who failed to csDMARDs received an induction therapy of MTX plus TNFi for maximally 12 weeks. Those achieving LDA in 12 weeks were randomly assigned at a 1:1:1 ratio into three groups: (A) adding hydroxychloroquine and sulfasalazine for the first 12 weeks and then discontinuing TNFi for the following 48 weeks; (B) maintaining TNFi and MTX for 60 weeks; and (C) maintaining TNFi and MTX for the first 12 weeks and then discontinuing TNFi for the following 48 weeks. The primary outcome was relapse.Results:A total of 117 patients were enrolled for induction therapy and 67 patients who achieved LDA within 12 weeks were randomized, with 24, 21, and 22 patients in groups A, B, and C, respectively. The relapse rates of groups A and B during the entire 60 weeks were comparable [10/22 (45.5%) vs. 7/20 (35.0%), χ² = 0.475, P = 0.491], however, significantly lower than that of group C [10/22 (45.5%) vs. 17/20 (85.0%), χ² = 5.517, P = 0.019; 7/20 (35.0%) vs. 17/20 (85.0%), χ² = 11.035, P = 0.004, respectively]. Taking RMB 100,000 Yuan as the threshold of willingness to pay, compared to MTX monotherapy (group C), both TNFi maintenance and triple csDMARDs therapies were cost-effective, but triple csDMARDs therapy was better.Conclusion:For RA patients who have achieved LDA with TNFi and MTX, csDMARDs triple therapy was a cost-effective option in favor of reducing relapse.Trial registration:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT02320630","term_id":"NCT02320630"}}NCT02320630.