Efficacy of Rituximab in a Frequently Relapsing Lupus Nephritis Cohort: Prior Response Shapes Current Flare Outcomes

Background: Refractory lupus nephritis(LN), characterized by a lack or inadequate response to standard immunosuppression, increases the risk of chronic kidney disease progression. Rituximab has been proposed as a rescue therapy. We aimed to evaluate the efficacy of rituximab in a frequently-relapsing LN Cohort. Methods: Retrospective cohort study. We included 90 patients with a history of at least 2 renal flares, that received rituximab for initial therapy. Patients were stratified based on their previous treatment-response according to KDIGO. We compared baseline variables at current flare presentation. Response to therapy and renal relapses were assessed by survival analyses. A multivariable Cox-regression was performed to evaluate variables associated with each outcome. Results: Of 90 patients, 23 (25%) had previous complete-response(CR), 42 (47%) partial-response (PR), and 25(28%) non-response(NR). The median follow-up was 32 months (IQR 19-47). Eighty-eight (98%) were female, with a median age of 32 years (IQR 26-37). The NR-group had higher serum creatinine (median 1.12 mg/dL, IQR 0.93-2.10, p=0.008) and uPCR (median 5.25 g/g, IQR 3.69-9.44, p=0.004). The overall response rate to rituximab therapy was 74.4%. In NR group, the 12th month CR and PR rates were 0% and 40%, respectively [Figure 1], and had a trend for faster time-to-relapse (median 8 months, 95%CI 4.30-11.70, p=0.079). In multivariableanalyses, the previous response to therapy was associated with response to current rituximab therapy (previous CR HR 3.26, 95%CI 1.51-7.01, previous PR HR 2.59, 95%CI 1.27-5.28). The previous response was also associated with time to renal flare (previous CR HR 0.35, 95%CI 0.14-0.93, previous PR HR 0.47, 95%CI 0.20-1.10). Conclusion: Rituximab therapy had a favorable overall efficacy in a frequently-relapsing LN cohort. Prior historical response of LN is associated with response and with the incidence of renal relapses.FIGURE 1: Kaplan-Meier Curves: Complete Response (A) and Partial Response (B) based on previous flare response.