#2427 A multi-targeted treatment approach to induce early remission in high-risk primary membranous nephropathy

Abstract

Abstract Background and Aims A considerable proportion of primary membranous nephropathy (PMN) patients do not achieve early clinical remission with current immunosuppression regimens. The goal of the study was to evaluate efficacy and safety of the multi-targeted treatment regimen including rituximab, cyclophosphamide, and corticosteroids (all administered at low cumulative doses) (RCP) in PMN with antibodies to the phospholipase A2 receptor (anti-PLA2R). Method The study enrolled 30 high- or very-high risk PMN patients with persistent nephrotic syndrome (NS) and elevated anti-PLA2R in a prospective single-arm study of RCP treatment. The experimental protocol consisted of a single intravenous infusion of RTX (375 mg/m2) and methylprednisolone (500 mg), followed by oral prednisolone (1 mg/kg) tapered rapidly at 10 mg per week and discontinued at week 49. An additional RTX infusion at the same dose was given during weeks 8-12, 20-24, and 32-36 if complete remission was not achieved and peripheral CD19+ cell exceeded 5 cells/μl. Four intravenous infusions of CYC were administered at a dose of 7.5 mg/kg every other week, in weeks 1, 3, 5, and 7. The effectiveness of RCP was compared to that of historic controls who received either rituximab-based therapy (RTX, n = 15) or cyclosporine+corticosteroids (CSA, n = 42). The primary outcomes measured were complete clinical remission (CR), overall remission (OR, which combines complete and partial remission) at month 12 after treatment initiation, and the time to clinical remission. Cox regression models were used to analyse the effect of RCP therapy on the probability of remission. Furthermore, we conducted comparative time-to-remission analyses in the RCP group and controls after propensity score (PS) matching. Results The RCP group exhibited higher OR and CR rates at 12 months (97% and 60%) compared to the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003) (Fig. 1A,B). The median time to OR was shorter in the RCP group (2.8 (1.6–3.9) months) than in the RTX group (7.1 (3.4–17.5) months, P = 0.008) and the CSA group (7.3 (6.0–13.6) months, P < 0.001) (Fig. 1A). In the adjusted Cox regression, the hazard ratios for OR and CR attainment for RCP compared to other treatments were 5.2 (95% CI: 2.8–9.6) and 4.8 (95% CI: 2.2–10.3), respectively. These results were confirmed by comparative analyses of propensity score-matched groups. Only one serious adverse event (SAE) occurred in the RCP group during the 56 patient-year follow-up. Conclusion RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.