The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy
Gema Fernández-Juárez, Jorge Rojas-Rivera, Anne-Els van de Logt, Joana Justino, Angel Sevillano, Fernando Caravaca-Fontán, Ana Ávila, Cristina Rabasco, Virginia Cabello, Alfonso Varela, Montserrat Díez, Guillermo Martín-Reyes, Marian Goicoechea Diezhandino, Luis F Quintana, Irene Agraz, Juan Ramón Gómez-Martino, Mercedes Cao, Antolina Rodríguez-Moreno, Begoña Rivas, Cristina Galeano, Jose Bonet, Ana Romera, Amir Shabaka, Emmanuelle Plaisier, Mario Espinosa, Jesus Egido, Alfonso Segarra, Gérard Lambeau, Pierre Ronco, Jack Wetzels, Manuel Praga, STARMEN Investigators, Manuel Praga, Angel Sevillano, Fernando Caravaca-Fontan, Hernando Trujillo, Eduardo Gutiérrez, Gema Fernandez Juarez, Amir Shabaka, Jorge Rojas-Rivera, Jesus Egido, Alberto Ortiz, Marian Goicoechea, Úrsula Verdalles, Alfons Segarra, Irene Agraz, Guillermo Martín-Reyes, Lara Perea, Ildefonso Valera, Mónica Martín, Virginia Cabello, Miguel Angel Pérez Valdivia, Luis F Quintana, Miquel Blasco, Mercedes Cao, Andrés López Muñiz, Ana Avila, Tamara Malek, Mario Espinosa, Cristina Rabasco, Montserrat Diaz, Iara DaSilva, Jordi Bonet, Maruja Navarro, Juan Ramón Gómez-Martino, Begoña Rivas, Antolina Rodríguez-Moreno, Cristina Galeano, Ana Romera, Ana Huerta, Ezequiel Rodríguez-Paternina, Ana Vigil, Roberto Alcázar, Vicente Paraíso, Vicente Barrio, Jack Wetzels, Anne-Els van de Logt, Julia Hofstra, Gema Fernández-Juárez, Jorge Rojas-Rivera, Anne-Els van de Logt, Joana Justino, Angel Sevillano, Fernando Caravaca-Fontán, Ana Ávila, Cristina Rabasco, Virginia Cabello, Alfonso Varela, Montserrat Díez, Guillermo Martín-Reyes, Marian Goicoechea Diezhandino, Luis F Quintana, Irene Agraz, Juan Ramón Gómez-Martino, Mercedes Cao, Antolina Rodríguez-Moreno, Begoña Rivas, Cristina Galeano, Jose Bonet, Ana Romera, Amir Shabaka, Emmanuelle Plaisier, Mario Espinosa, Jesus Egido, Alfonso Segarra, Gérard Lambeau, Pierre Ronco, Jack Wetzels, Manuel Praga, STARMEN Investigators, Manuel Praga, Angel Sevillano, Fernando Caravaca-Fontan, Hernando Trujillo, Eduardo Gutiérrez, Gema Fernandez Juarez, Amir Shabaka, Jorge Rojas-Rivera, Jesus Egido, Alberto Ortiz, Marian Goicoechea, Úrsula Verdalles, Alfons Segarra, Irene Agraz, Guillermo Martín-Reyes, Lara Perea, Ildefonso Valera, Mónica Martín, Virginia Cabello, Miguel Angel Pérez Valdivia, Luis F Quintana, Miquel Blasco, Mercedes Cao, Andrés López Muñiz, Ana Avila, Tamara Malek, Mario Espinosa, Cristina Rabasco, Montserrat Diaz, Iara DaSilva, Jordi Bonet, Maruja Navarro, Juan Ramón Gómez-Martino, Begoña Rivas, Antolina Rodríguez-Moreno, Cristina Galeano, Ana Romera, Ana Huerta, Ezequiel Rodríguez-Paternina, Ana Vigil, Roberto Alcázar, Vicente Paraíso, Vicente Barrio, Jack Wetzels, Anne-Els van de Logt, Julia Hofstra
Abstract
A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.
Keywords: corticosteroids; cyclophosphamide; primary membranous nephropathy; rituximab; tacrolimus.
Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
Source: PubMed