Three-Year Results of Tapering Tumor Necrosis Factor Inhibitor to Withdrawal Compared to Stable Tumor Necrosis Factor Inhibitor Among Patients With Rheumatoid Arthritis in Sustained Remission: A Multicenter Randomized Trial.

Abstract

Tapering of tumor necrosis factor inhibitor (TNFi) treatment in rheumatoid arthritis (RA) remission is debated. We assessed the effect of tapering TNFi to withdrawal versus continued stable TNFi on flare-free survival and joint damage progression over three years. ARCTIC REWIND was a multicenter open-label, noninferiority trial that included patients with RA in remission for ≥12 months taking stable TNFi therapy. Patients were randomized 1:1 to taper TNFi to withdrawal or continue stable treatment. The primary end points of the current study were flare-free survival and radiographic progression over three years. Flare-free survival was analyzed by Kaplan-Meier methods, flare rates were analyzed by Cox regression, and radiographic progression was analyzed by logistic mixed-effects models. Of 99 randomized patients, 92 received the allocated therapy, and 80 completed the three-year follow-up. The mean baseline Disease Activity Score based on the 44 joint count was 0.8, and conventional synthetic disease-modifying antirheumatic drug comedication was used by 90% of patients. After three years, 25% (95% confidence interval [CI] 13%-38%) remained flare free in the tapering TNFi group, compared to 85% (95% CI 70%-93%) in the stable group, and the corresponding hazard ratio for flare was 9.4 (95% CI 3.9-22.8, P < 0.0001). In the tapering group, 6 of 41 (15%) experienced radiographic progression, compared with 3 of 38 (8%) in the stable group (risk difference 6.7%, 95% CI -7.1% to 20.5%, P = 0.3). Adverse events occurred in 81% of the patients in the tapering group and 89% of the patients in the stable group. In contrast to those receiving stable TNFi treatment, a minority of patients with RA in remission tapering TNFi to withdrawal remained flare free over three years. There was no statistically significant difference in radiographic progression between the groups.