THE ASSOCIATION OF RITUXIMAB- VS. CYCLOPHOSPHAMIDE-BASED REMISSION INDUCTION STRATEGIES WITH RISK OF END-STAGE RENAL DISEASE AND DEATH IN ANCA-ASSOCIATED VASCULITIS
Authors: Zachary Wallace et al.
The RAVE trial established the non-inferiority of rituximab (RTX) vs cyclophosphamide (CYC) for remission induction of ANCA-Associated Vasculitis (AAV). However, little is known regarding the long-term outcomes of these remission induction strategies in real world practice. This study calculated the risks of the two strategies on end-stage renal disease (ESRD) and death, two key outcomes in AAV.
The data source was a consecutive inception cohort of PR3- or MPO-ANCA+ AAV patients assembled in a large healthcare system between 2002 and 2019. The primary exposure was RTX- vs CYC-based remission induction regimens. ESRD and vital status, the composite outcome of interest, were ascertained by review as well as linkage to the United States Renal Data System and National Death Index, respectively. A propensity score (PS) model for treatment with RTX vs CYC was created using demographic and disease-specific variables present at baseline, including age, sex, comorbidities, ANCA type, AAV manifestations, and renal function.
553 patients received RTX- or CYC-based regimens. The mean (SD) age was 59.6 (17.5) years, 236 (43%) were male, and 475 (86%) were white. The majority were MPO-ANCA+ (379, 68%) and had renal involvement (376, 68%). The mean (SD) BVAS/WG score was 5.1 (2.2). RTX-users had a higher BVAS/WG (5.3 [2.4] vs 4.8 [1.9], p=0.004) and CYC-users had a higher creatinine (2.4 [1.2, 5.2] vs 1.2 [1.0, 3.5], p< 0.001). Over a total follow-up of 64,686 days, there were 182 events (ESRD or death). The incidence of the primary outcome was 3.0/1,000 days in RTX-users vs 2.7/1,000 days in CYC-users.
In the multivariable adjusted Cox model (n=553), the risk of ESRD or death was similar in RTX- vs CYC-users (1.26, 95% CI 0.89 to 1.79). The results remained similar in analyses limited to those with renal involvement and those with any major disease. Baseline demographics and disease-specific features were well-balanced after PS-matching. In the PS-matched analysis (n=351), the risk of ESRD or death was similar in RTX- vs CYC-users (1.19, 95% CI 0.75-1.89).
In this large multi-center AAV cohort, there were no significant differences in the risk of ESRD or death associated with RTX- vs CYC-based therapy for remission induction. The observations remained consistent in analyses using propensity score matching to robustly address confounding by indication. The fact that RTX based therapy did not perform better than a CYC-based is reassuring. It allows us an individualized choice of the initial immunosuppression.