Roberta Fenoglio1, Simone Baldovino1, Savino Sciascia1, Emanuele De Simone1, Giulio Del Vecchio1, Michela Ferro1, Giacomo Quattrocchio1, Carla Naretto1, Dario Roccatello2. 1. CMID-Nephrology and Dialysis Unit (ERK-Net Member), Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, University of Turin and San Giovanni Bosco Hospital, Piazza del Donatore di Sangue 3, 10054, Turin, Italy. 2. CMID-Nephrology and Dialysis Unit (ERK-Net Member), Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, University of Turin and San Giovanni Bosco Hospital, Piazza del Donatore di Sangue 3, 10054, Turin, Italy. dario.roccatello@unito.it.
Abstract
BACKGROUND: Patients (pts) with primary Membranous nephropathy (MN) have an autoimmune disease caused by autoantibodies against podocyte antigens and 60-80% of them have antibodies directed against the M-type phospholipase A2 receptor (PLA2R). Immunosuppressive treatment is recommended in high-medium risk pts. Recently the use of rituximab (RTX), has emerged as an important therapeutic option in pts with primary MN. The appropriate cumulative dose of RTX in PMN pts is still uncertain, and favorable outcomes even with low-dose of RTX has been described. We compared efficacy and safety of 3 different treatment regimens: low-dose RTX (Protocol 1, one dose of RTX 375 mg/m2), standard RTX protocol (Protocol 2, four weekly doses of rituximab 375 mg/m2) and Ponticelli's regimen. METHODS: 42 pts with primary MN and nephrotic syndrome were assigned to Protocol 1 (14 pts) or Protocol 2 (14 pts). All patients were followed for 24 months after RTX. Fourteen pts, matched for age and baseline serum creatinine (sCr) and proteinuria, treated with Ponticelli's regimen were examined as controls. RESULTS: At 24 months, a significant improvement in proteinuria levels was observed in pts treated with Protocol 1 (7.5 ± 4.8 at T0; 0.21 ± 0.15 at T24, p < 0.01), Protocol 2 (5.1 ± 1.41 g/24 at T0; 0.35 ± 0.39 at T24 p < 0.01) and controls (8.27 ± 4.78 T0; 2.2 ± 1.9 g/24 h at T24, p < 0.01). No differences in clinical response (p = 0.53) was observed comparing the 3 groups. CONCLUSIONS: Our data suggest that the RTX is a promising alternative to Ponticelli's regimen even at low-doses. This makes RTX a cost-effective treatment of primary MN in the short and medium terms.
BACKGROUND:Patients (pts) with primary Membranous nephropathy (MN) have an autoimmune disease caused by autoantibodies against podocyte antigens and 60-80% of them have antibodies directed against the M-type phospholipase A2 receptor (PLA2R). Immunosuppressive treatment is recommended in high-medium risk pts. Recently the use of rituximab (RTX), has emerged as an important therapeutic option in pts with primary MN. The appropriate cumulative dose of RTX in PMN pts is still uncertain, and favorable outcomes even with low-dose of RTX has been described. We compared efficacy and safety of 3 different treatment regimens: low-dose RTX (Protocol 1, one dose of RTX 375 mg/m2), standard RTX protocol (Protocol 2, four weekly doses of rituximab 375 mg/m2) and Ponticelli's regimen. METHODS: 42 pts with primary MN and nephrotic syndrome were assigned to Protocol 1 (14 pts) or Protocol 2 (14 pts). All patients were followed for 24 months after RTX. Fourteen pts, matched for age and baseline serum creatinine (sCr) and proteinuria, treated with Ponticelli's regimen were examined as controls. RESULTS: At 24 months, a significant improvement in proteinuria levels was observed in pts treated with Protocol 1 (7.5 ± 4.8 at T0; 0.21 ± 0.15 at T24, p < 0.01), Protocol 2 (5.1 ± 1.41 g/24 at T0; 0.35 ± 0.39 at T24 p < 0.01) and controls (8.27 ± 4.78 T0; 2.2 ± 1.9 g/24 h at T24, p < 0.01). No differences in clinical response (p = 0.53) was observed comparing the 3 groups. CONCLUSIONS: Our data suggest that the RTX is a promising alternative to Ponticelli's regimen even at low-doses. This makes RTX a cost-effective treatment of primary MN in the short and medium terms.
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