The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy
Fernández-Juárez, Gema (Hospital Universitario Fundación Alcorcón)
Rojas-Rivera, Jorge E. (Hospital Universitario Fundación Jiménez Díaz)
Logt, Anne-Els van de (Radboud University Medical Center)
Justino, Joana (Université Côte d'Azur. Institut de Pharmacologie Moléculaire et Cellulaire (Valbonne, França))
Sevillano Prieto, Angel Manuel (Hospital Universitario 12 de Octubre (Madrid))
Caravaca-Fontan, Fernando (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Ávila, Ana (Hospital Universitari Doctor Peset (València))
Rabasco, Cristina (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Cabello, Virginia (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Varela, Alfonso (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Díaz Encarnación, Montserrat Mercedes (Institut d'Investigació Biomèdica Sant Pau)
Martín-Reyes, Guillermo (Hospital Regional Universitario de Málaga)
Goicoechea, Marian (Hospital General Universitario Gregorio Marañón)
Quintana, Luis F. (Centro de Referencia en Enfermedad Glomerular Compleja del Sistema Nacional de Salud)
Agraz Pamplona, Irene (Hospital Universitari Vall d'Hebron)
Gómez-Martino, Juan Ramón (Hospital San Pedro de Alcántara)
Cao, Mercedes (Complejo Hospitalario Universitario de A Coruña)
Rodríguez-Moreno, Antolina (Hospital Clínico San Carlos (Madrid))
Rivas, Begoña (Hospital Universitario La Paz (Madrid))
Galeano Alvarez, Cristina (Hospital Universitario Ramón y Cajal (Madrid))
Bonet, Jose (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Romera, Ana (Hospital General de Ciudad Real)
Shabaka, Amir (Hospital Universitario Fundación Alcorcón)
Plaisier, Emmanuelle (Centre de Référence Maladies Rares Syndrome Néphrotique Idiopathique (Niça, França))
Espinosa, Mario (Hospital Universitario Reina Sofía (Còrdova, Espanya))
Egido de los Rios, Jesus (Hospital Universitario Fundación Jiménez Díaz)
Segarra-Medrano, Alfonso (Hospital Universitari Vall d'Hebron)
Lambeau, Gérard (Institut de Pharmacologie Moléculaire et Cellulaire (Valbonne, França))
Ronco, Pierre (Centre de Référence Maladies Rares Syndrome Néphrotique Idiopathique (Niça, França))
Wetzels, Jack (Radboud University Medical Center)
Praga, Manuel (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Caravaca-Fontan, Fernando (Hospital Universitario 12 de Octubre (Madrid))
Trujillo, Hernando (Hospital Universitario 12 de Octubre (Madrid))
Gutiérrez, Eduardo (Hospital Universitario 12 de Octubre (Madrid))
Ortiz, Alberto (Hospital Universitario Fundación Jiménez Díaz)
Goicoechea, Marian (Hospital General Universitario Gregorio Marañón)
Verdalles, Úrsula (Hospital General Universitario Gregorio Marañón)
Segarra, Alfons (Hospital Universitari Vall d'Hebron)
Perea, Lara (Hospital Universitari Vall d'Hebron)
Valera, Ildefonso (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Martín, Mónica (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Pérez Valdivia, Miguel Angel (Hospital Universitario Virgen del Rocío (Sevilla, Andalusia))
Blasco, Miquel Angel (Hospital Clínic i Provincial de Barcelona)
López Muñiz, Andrés (Complejo Hospitalario Universitario de A Coruña)
Malek, Tamara (Hospital Universitari Doctor Peset (València))
DaSilva Santos, Iara
Bonet, Jordi (Institut Germans Trias i Pujol)
Navarro, Maruja Isabel (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Huerta, Ana (Hospital Universitario Puerta de Hierro Majadahonda (Madrid))
Rodríguez-Paternina, Ezequiel (Hospital Universitario de Getafe (Madrid))
Vigil, Ana (Hospital Universitario Severo Ochoa)
Alcázar, Roberto (Hospital Universitario Infanta Leonor)
Paraíso, Vicente (Hospital Universitario del Henares ( Madrid))
Barrio, Vicente (Hospital Universitario Infanta Sofía (San Sebastián de los Reyes))
Hofstra, Julia (Radboud University Medical Center)
Universitat Autònoma de Barcelona

Date:	2021
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.
Grants:	Instituto de Salud Carlos III PI13/02495 Instituto de Salud Carlos III ICI14/00350 Instituto de Salud Carlos III RD12/0021/0029
Note:	Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Red de Investigación Renal (RedInRen); European Renal Association-European Dialysis and Transplant Association (ERA-EDTA); Fundación Renal Iñigo Álvarez de Toledo (FRIAT); Fundación para la Investigación Biomédica Hospital 12 de Octubre (i+12); Centre National de la Recherche Scientifique; Fondation Maladies Rares (LAM-RD_20170304); National Research Agency (ANR, grants MNaims ANR-17-CE17-0012-01); "Investments for the Future" Laboratory of Excellence SIGNALIFE, a network for innovation on signal transduction pathways in life sciences (ANR-11-LABX-0028-01); Initiative of Excellence (IDEX; UCAJedi ANR-15-IDEX-01); Fondation pour la Recherche Médicale (FRM, ING20140129210, DEQ20180339193, FDT201805005509).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Corticosteroids ; Cyclophosphamide ; Primary membranous nephropathy ; Rituximab ; Tacrolimus
Published in:	Kidney International, Vol. 99 Núm. 4 (april 2021) , p. 986-998, ISSN 1523-1755

DOI: 10.1016/j.kint.2020.10.014
PMID: 33166580

13 p, 1.4 MB

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