Continuation Versus Temporary Interruption of Immunomodulatory Agents During Infections in Patients With Inflammatory Rheumatic Diseases: A Randomized Controlled Trial

Abstract Background Immunomodulatory agents (IA) are commonly used to treat inflammatory rheumatic diseases (IRDs). Guidelines typically recommend temporarily interrupting IA during infections, but evidence supporting this approach is limited and continuation may be equally safe or even preferable. The objective of this study was to compare these 2 treatment strategies. Methods We conducted a large multi-center, open-label, randomized controlled trial (Dutch Trial Register (NL8922), in which infection-free IRD patients on IA were randomized 1:1 to either continue or temporarily interrupt IA treatment when experiencing their first clinically relevant infection. Primary outcome was the proportion of patients with a serious infection (requiring hospitalization or intravenous treatment), analyzed in the modified intention-to-treat (mITT) population using the Cochran-Mantel-Haenszel method. The mITT population included all patients who experienced a clinically relevant infection during follow-up. Secondary analyses included Complier Average Causal Effect (CACE) models to account for non-adherence. Results Of 1142 patients enrolled (1667 patient years of follow-up), 474 developed a clinically relevant infection (mITT population). Serious infections occurred in 12 of 233 patients (5.15%) in the interruption group and in 9 of 241 (3.73%) in the continuation group, adjusted risk difference was 1.71% (95% CI −1.99 to 5.39). CACE analysis showed a risk difference of 4.51 (95% confidence interval [CI]: −7.32 to 16.34) in favor of continuation. Conclusions These findings suggest that temporary interruption and continuation of IA result in similar risk and outcome of infections in IRD patients. Although his study is limited by low statistical power, the findings suggest that continuation of IA during an infection is safe.