The Effect of Achieving Serologic Remission on Subsequent Risk of Relapse, End-Stage Renal Disease, and Mortality in ANCA-Associated Vasculitis: A Target Trial Emulation Study

OBJECTIVE: To evaluate the effect of achieving a negative post-induction ANCA assay on the risk of relapse, end stage renal disease (ESRD), and death in ANCA-associated vasculitis (AAV). METHODS: We emulated a target trial using observational data from the Mass General Brigham AAV cohort comparing patients who achieved vs. did not achieve serologic remission (negative ANCA assay) within 180 days of induction. Outcomes were relapse, ESRD, or death within 5 years, obtained from medical records, the US Renal Data System, and the National Death Index. We placed a “clone” of each patient in both trial arms, censored those deviating from their assigned protocol, and weighted each by the inverse probability of censoring. Outcomes were assessed by pooled logistic regression. RESULTS: The study included 506 AAV patients. The mean age was 61 years (SD 18) and the majority were female (58%), White (87%), MPO-ANCA+ (72%) and had renal involvement (68%). Rituximab (59%) or cyclophosphamide (33%) was most often used for induction treatment. Within 5 years, 81 (16%) died, 51 (10%) had ESRD, and 64 (13%) had relapse. Patients treated to a negative ANCA assay within 180 days had hazard ratio (HR) 0.55 (95%CI 0.38 to 0.81) for relapse and HR 0.87 (95%CI 0.61 to 1.25) for the composite of ESRD or death within 5 years. CONCLUSIONS: In this emulated target trial from a large AAV cohort, achieving serologic remission within 180 days of induction was associated with lower risk of relapse, but no statistically significant difference in ESRD or mortality outcomes.