Document Detail


Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis.
MedLine Citation:
PMID:  22087680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.).
Authors:
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;
Publication Detail:
Type:  Clinical Trial, Phase III; Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The New England journal of medicine     Volume:  365     ISSN:  1533-4406     ISO Abbreviation:  N. Engl. J. Med.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-17     Completed Date:  2011-12-07     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  0255562     Medline TA:  N Engl J Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1886-95     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University of North Carolina, Chapel Hill, USA. neil.solomons@viforpharma.com
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00377637
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Azathioprine / adverse effects,  therapeutic use*
Female
Humans
Immunosuppressive Agents / adverse effects,  therapeutic use*
Infection / etiology
Kaplan-Meier Estimate
Lupus Nephritis / drug therapy*
Maintenance Chemotherapy
Male
Middle Aged
Mycophenolic Acid / adverse effects,  analogs & derivatives*,  therapeutic use
Patient Dropouts
Recurrence / prevention & control
Young Adult
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 24280-93-1/Mycophenolic Acid; 446-86-6/Azathioprine; 9242ECW6R0/mycophenolate mofetil
Investigator
Investigator/Affiliation:
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 /
Comments/Corrections
Comment In:
N Engl J Med. 2011 Nov 17;365(20):1929-30   [PMID:  22087685 ]
N Engl J Med. 2012 Feb 9;366(6):572; author reply 573   [PMID:  22316460 ]
N Engl J Med. 2012 Feb 9;366(6):572; author reply 573   [PMID:  22316459 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Childhood adiposity, adult adiposity, and cardiovascular risk factors.
Next Document:  Extracorporeal membrane oxygenation for ARDS in adults.