Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis
Mary Anne Dooley, David Jayne, Ellen M Ginzler, David Isenberg, Nancy J Olsen, David Wofsy, Frank Eitner, Gerald B Appel, Gabriel Contreras, Laura Lisk, Neil Solomons, ALMS Group, Carlos Abud, Sharon Adler, Graciela Alarc, Elisa Albuquerque, Fernando Almeida, Alejandro Alvarellos, Gerald Appel, Hilario Avila, Juan I Menchaca, Cornelia Blume, Ioannis Boletis, Alain Bonnardeaux, Alan Braun, Jill Buyon, Ricard Cervera, Nan Chen, Shunle Chen, Gabriel Contreras, António Gomes Da Costa, Razeen Davids, David D'Cruz, Enrique De Ramón, Carlos Haya, Atul Deodhar, Mary Anne Dooley, Andrea Doria, Bertrand Dussol, Paul Emery, Justus Fiechtner, Jürgen Floege, Hilda Fragoso-Loyo, Richard Furie, Rozina Ghazalli, Cybele Ghossein, Gary Gilkeson, Ellen Ginzler, 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, Claude Bernard, Pablo Monge, Saraladev Naicker, Nathaniel Neal, Michael Neuwelt, C Michael Neuwelt, Kathy Nicholls, Nancy Olsen, Jose Ordi-Ros, Barbara Ostrov, Milton S Hershey, Manuel Pestana, Michelle Petri, Gyula Pokorny, Jacques Pourrat, Jiaqi Qian, Jai Radhakrishnan, Brad Rovin, Jorge Sánchez-Guerrero, Julio Sanchez Roman, Joseph Shanahan, William Shergy, Fotini Skopouli, Alberto Spindler, Christopher Striebich, Robert Sundel, Charles Swanepoel, Si Yen Tan, Guillermo Tate, Vladimír Tesaŕ, Mohamed Tikly, Haiyan Wang, Rosnawati Yahya, Xueqing Yu, Fengchun Zhang, Diana Zoruba, Bernardo Houssay, Peter Carson, Michael Snaith, Daniel Cattran, Mary Anne Dooley, David Jayne, Ellen M Ginzler, David Isenberg, Nancy J Olsen, David Wofsy, Frank Eitner, Gerald B Appel, Gabriel Contreras, Laura Lisk, Neil Solomons, ALMS Group, Carlos Abud, Sharon Adler, Graciela Alarc, Elisa Albuquerque, Fernando Almeida, Alejandro Alvarellos, Gerald Appel, Hilario Avila, Juan I Menchaca, Cornelia Blume, Ioannis Boletis, Alain Bonnardeaux, Alan Braun, Jill Buyon, Ricard Cervera, Nan Chen, Shunle Chen, Gabriel Contreras, António Gomes Da Costa, Razeen Davids, David D'Cruz, Enrique De Ramón, Carlos Haya, Atul Deodhar, Mary Anne Dooley, Andrea Doria, Bertrand Dussol, Paul Emery, Justus Fiechtner, Jürgen Floege, Hilda Fragoso-Loyo, Richard Furie, Rozina Ghazalli, Cybele Ghossein, Gary Gilkeson, Ellen Ginzler, 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, Claude Bernard, Pablo Monge, Saraladev Naicker, Nathaniel Neal, Michael Neuwelt, C Michael Neuwelt, Kathy Nicholls, Nancy Olsen, Jose Ordi-Ros, Barbara Ostrov, Milton S Hershey, Manuel Pestana, Michelle Petri, Gyula Pokorny, Jacques Pourrat, Jiaqi Qian, Jai Radhakrishnan, Brad Rovin, Jorge Sánchez-Guerrero, Julio Sanchez Roman, Joseph Shanahan, William Shergy, Fotini Skopouli, Alberto Spindler, Christopher Striebich, Robert Sundel, Charles Swanepoel, Si Yen Tan, Guillermo Tate, Vladimír Tesaŕ, Mohamed Tikly, Haiyan Wang, Rosnawati Yahya, Xueqing Yu, Fengchun Zhang, Diana Zoruba, Bernardo Houssay, Peter Carson, Michael Snaith, Daniel Cattran
Abstract
Background: Maintenance therapy, often with azathioprine or mycophenolate mofetil, is required to consolidate remission and prevent relapse after the initial control of lupus nephritis.
Methods: We carried out a 36-month, randomized, double-blind, double-dummy, phase 3 study comparing oral mycophenolate mofetil (2 g per day) and oral azathioprine (2 mg per kilogram of body weight per day), plus placebo in each group, in patients who met response criteria during a 6-month induction trial. The study group underwent repeat randomization in a 1:1 ratio. Up to 10 mg of prednisone per day or its equivalent was permitted. The primary efficacy end point was the time to treatment failure, which was defined as death, end-stage renal disease, doubling of the serum creatinine level, renal flare, or rescue therapy for lupus nephritis. Secondary assessments included the time to the individual components of treatment failure and adverse events.
Results: A total of 227 patients were randomly assigned to maintenance treatment (116 to mycophenolate mofetil and 111 to azathioprine). Mycophenolate mofetil was superior to azathioprine with respect to the primary end point, time to treatment failure (hazard ratio, 0.44; 95% confidence interval, 0.25 to 0.77; P = 0.003), and with respect to time to renal flare and time to rescue therapy (hazard ratio, <1.00; P < 0.05). Observed rates of treatment failure were 16.4% (19 of 116 patients) in the mycophenolate mofetil group and 32.4% (36 of 111) in the azathioprine group. Adverse events, most commonly minor infections and gastrointestinal disorders, occurred in more than 95% of the patients in both groups (P = 0.68). Serious adverse events occurred in 33.3% of patients in the azathioprine group and in 23.5% of those in the mycophenolate mofetil group (P = 0.11), and the rate of withdrawal due to adverse events was higher with azathioprine than with mycophenolate mofetil (39.6% vs. 25.2%, P = 0.02).
Conclusions: Mycophenolate mofetil was superior to azathioprine in maintaining a renal response to treatment and in preventing relapse in patients with lupus nephritis who had a response to induction therapy. (Funded by Vifor Pharma [formerly Aspreva]; ALMS ClinicalTrials.gov number, NCT00377637.).
Source: PubMed