Mycophenolate Mofetil in C3 Glomerulopathy and Pathogenic Drivers of the Disease
Fernando Caravaca‐Fontán, Montserrat M. Díaz Encarnación, Laura Lucientes, Teresa Cavero, Virginia Cabello, Gema Ariceta, Luís F. Quintana, Helena Marco, Xoana Barros, Natàlia Ramos, Nuria Rodríguez-Mendiola, Sonia Cruz, Gema Fernández‐Juárez, A. Bernardos Rodríguez, Ana Pérez de José, Cristina Rabasco, Raquél Rodado, Loreto Fernández, María Vanessa Pérez-Gómez, Ana I Ávila, Luis Eduardo Bravo, Javier Lumbreras, Natalia Allende, María Dolores Sánchez de la Nieta, Eva Rodríguez, Teresa Olea, Marta Melgosa, Ana Huerta, Rosa Miquel, Carmen Mon, Gloria Fraga, Alberto de Lorenzo, Juliana Draibe, Marta Cano-Megías, Fayna González, Amir Shabaka, Maria Esperanza López-Rubio, María Ángeles Fenollosa, Luis Martín‐Penagos, Iara Da Silva, Juana Alonso Titos, Santiago Rodrı́guez de Córdoba, Elena Goicoechea de Jorge, Manuel Praga, on behalf of the Spanish Group for the Study of Glomerular Diseases GLOSEN
Abstract
BACKGROUND AND OBJECTIVES: C3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: =16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure). RESULTS: The study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse. CONCLUSIONS: The beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study.