Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis

verfasst von: Gerald B. Appel, Gabriel Contreras, Mary Anne Dooley, Ellen M. Ginzler, David Isenberg, David Jayne, Lei Shi Li, Eduardo Mysler, Jorge Sánchez-Guerrero, Neil Solomons, David Wofsy, Carlos Abud, Sharon Adler, Graciela Alarcón, Elisa Albuquerque, Fernando Almeida, Alejandro Alvarellos, Gerald Appel, Hilario Avila, Cornelia Blume, Ioannis Boletis, Alain Bonnardeaux, Alan Braun, Jill Buyon, Ricard Cervera, Nan Chen, Shunle Chen, António Gomes Da Costa, Razeen Davids, David D'Cruz, Enrique De Ramón, Atul Deodhar, Andrea Doria, Bertrand Dussol, Paul Emery, Justus Fiechtner, Jürgen Floege, Hilda Fragoso-Loyo, Richard Furie, Rozina Ghazalli, Cybele Ghossein, Gary Gilkeson, Ellen Ginzler, Caroline Gordon, Jennifer Grossman, Jieruo Gu, Loïc Guillevin, Pierre Yves Hatron, Gisela Herrera, Falk Hiepe, Frederic Houssiau, Osvaldo Hübscher, Claudia Hura, Joshua Kaplan, Gianna Kirsztajn, Emese Kiss, Ghazali Ahmad Kutty, Maurice Laville, Maria Lazaro, Oliver Lenz, Leishi Li, Liz Lightstone, Sam Lim, Michel Malaise, Susan Manzi, Juan Marcos, Olivier Meyer, Pablo Monge, Saraladev Naicker, Nathaniel Neal, Michael Neuwelt, Kathy Nicholls, Nancy Olsen, Jose Ordi-Ros, Barbara Ostrov, Manuel Pestana, Michelle Petri, Gyula Pokorny, Jacques Pourrat, Jiaqi Qian, Jai Radhakrishnan, Brad Rovin, Julio Sanchez Roman, Joseph Shanahan, William Shergy, Fotini Skopouli, Alberto Spindler, Christopher Striebich, Robert Sundel, Charles Swanepoel, Yen Tan Si, Guillermo Tate, Vladimír Tesaŕ, Mohamed Tikly, Haiyan Wang, Rosnawati Yahya, Xueqing Yu, Fengchun Zhang, Diana Zoruba
Abstract: Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m² in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.
Externe Organisation(en): Columbia University
University of Miami (UM)
University of North Carolina
SUNY Downstate Medical Center
University College London (UCL)
Addenbrooke's Hospital
Nanjing General Hospital of People's Liberation Army (NGH)
Organización Médica de Investigación (OMI)
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Aspreva Pharmaceuticals Corporation
University of California at San Francisco
Hospital Central Dr Ignacio Morones Prieto
University of California (UCLA)
University of Alabama at Birmingham
Universidade do Estado do Rio de Janeiro
Centro de Ciências Médicas e Biológicas de Sorocaba (CCMB)
Hospital Privado Universitario de Córdoba
Universidad de Guadalajara
Universitätsklinikum Düsseldorf
Laiko Hospital
Polyclinique Médicale Concorde (PMC)
Mercy Arthritis And Osteoporosis Center
New York University (NYU)
Universitat de Barcelona (UB)
Shanghai Jiaotong University
Universidade de Lisboa
University of Stellenbosch
St. Thomas' Hospital
Hospital Regional Universitario Carlos Haya
Oregon Health and Science University
Università degli Studi di Padova
Hopital de La Conception
University of Leeds
Rheinisch-Westfälische Technische Hochschule Aachen (RWTH)
North Shore-Long Island Jewish Health System
Penang Adventist Hospital
Northwestern University
Medical University of South Carolina
University of Birmingham
Sun Yat-Sen University
Universite Paris 5
Université de Lille 2
Hospital CIMA
Charité - Universitätsmedizin Berlin
Katholische Universität Löwen (UCL)
Centro de Educacion Medica e Investigaciones Clinicas Norberto Quirno
San Antonio Kidney
Rutgers - The State University of New Jersey, Newark
Universidade Federal de Sao Paulo
University of Debrecen
Hospital Selayang
Hopital Edouard Herriot
Fundación CIDEA
Imperial College London
Emory University
Université de Liège
University of Pittsburgh
Hospital Interzonal General de Agudos General José de San Martín
Université Paris VII
Centro Médico Integral (CMI)
University of the Witwatersrand
Valerius Medical Group and Research Center of Greater Long Beach
MD Inc. Emergency Physicians
Royal Melbourne Hospital
University of Texas Southwestern Medical Center
Universidad Autónoma de Barcelona (UAB)
Pennsylvania State University
Sao Joao Hospital
Johns Hopkins University
University of Szeged
Hopital de Rangueil
The Ohio State University
Hospital Universitario Virgen del Rocio
Duke University Medical Center
Rheumatology Associates of North Alabama (RANA)
Athens Euroclinic
Centro Medico Privado de Reumatologia
University of Colorado Anschutz Medical Campus
Harvard University
Universität Kapstadt (UCT)
Universiti Malaya (UM)
Charles University
Chris Hani Baragwanath Hospital
Peking University First Hospital
Kuala Lumpur Hospital
Peking Union Medical College
Vicente López
Typ: Artikel
Journal: Journal of the American Society of Nephrology
Band: 20
Seiten: 1103-1112
Anzahl der Seiten: 10
ISSN: 1046-6673
Publikationsdatum: 05.2009
Publikationsstatus: Veröffentlicht
Peer-reviewed: Ja
ASJC Scopus Sachgebiete: Nephrologie
Elektronische Version(en): https://doi.org/10.1681/ASN.2008101028 (Zugang: Offen)

BibTeX

@article{5fc81ee7789940d6a9764086644074b0,
title = "Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis",
abstract = "Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m2 in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.",
author = "Appel, {Gerald B.} and Gabriel Contreras and Dooley, {Mary Anne} and Ginzler, {Ellen M.} and David Isenberg and David Jayne and Li, {Lei Shi} and Eduardo Mysler and Jorge S{\'a}nchez-Guerrero and Neil Solomons and David Wofsy and Carlos Abud and Sharon Adler and Graciela Alarc{\'o}n and Elisa Albuquerque and Fernando Almeida and Alejandro Alvarellos and Gerald Appel and Hilario Avila and Cornelia Blume and Ioannis Boletis and Alain Bonnardeaux and Alan Braun and Jill Buyon and Ricard Cervera and Nan Chen and Shunle Chen and {Da Costa}, {Ant{\'o}nio Gomes} and Razeen Davids and David D'Cruz and {De Ram{\'o}n}, Enrique and Atul Deodhar and Andrea Doria and Bertrand Dussol and Paul Emery and Justus Fiechtner and J{\"u}rgen Floege and Hilda Fragoso-Loyo and Richard Furie and Rozina Ghazalli and Cybele Ghossein and Gary Gilkeson and Ellen Ginzler and Caroline Gordon and Jennifer Grossman and Jieruo Gu and Lo{\"i}c Guillevin and Hatron, {Pierre Yves} and Gisela Herrera and Falk Hiepe and Frederic Houssiau and Osvaldo H{\"u}bscher and Claudia Hura and Joshua Kaplan and Gianna Kirsztajn and Emese Kiss and Kutty, {Ghazali Ahmad} and Maurice Laville and Maria Lazaro and Oliver Lenz and Leishi Li and Liz Lightstone and Sam Lim and Michel Malaise and Susan Manzi and Juan Marcos and Olivier Meyer and Pablo Monge and Saraladev Naicker and Nathaniel Neal and Michael Neuwelt and Kathy Nicholls and Nancy Olsen and Jose Ordi-Ros and Barbara Ostrov and Manuel Pestana and Michelle Petri and Gyula Pokorny and Jacques Pourrat and Jiaqi Qian and Jai Radhakrishnan and Brad Rovin and Roman, {Julio Sanchez} and Joseph Shanahan and William Shergy and Fotini Skopouli and Alberto Spindler and Christopher Striebich and Robert Sundel and Charles Swanepoel and Si, {Yen Tan} and Guillermo Tate and Vladim{\'i}r Tesa{\'r} and Mohamed Tikly and Haiyan Wang and Rosnawati Yahya and Xueqing Yu and Fengchun Zhang and Diana Zoruba",
year = "2009",
month = may,
doi = "10.1681/ASN.2008101028",
language = "English",
volume = "20",
pages = "1103--1112",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "5",
}