title: Immunosuppressive Therapies for the Maintenance Treatment of Proliferative Lupus Nephritis: A Systematic Review and Network Metaanalysis.
abstract: OBJECTIVE
  To determine the most effective immunosuppressive therapy for the longterm management of proliferative lupus nephritis (PLN) based on the outcome of renal failure.
  
  
  METHODS
  A systematic review of randomized controlled trials (RCT) was conducted. MEDLINE and EMBASE were searched. RCT designed to examine the maintenance treatment effectiveness of immunosuppressive agents for PLN were included. A Bayesian network metaanalysis of 2-arm and 3-arm trials was used. A skeptical prior assumption was used in sensitivity analysis. Four immunosuppressive agents were evaluated: cyclophosphamide (CYC), azathioprine (AZA), mycophenolate mofetil (MMF), and prednisone alone. The outcome of interest was renal failure during the study period, defined by serum creatinine (sCr) > 256 µmol/l, doubling of sCr from baseline, and/or endstage renal disease.
  
  
  RESULTS
  The OR (95% credible interval) of developing renal failure at 2-3 years was 0.72 (0.11, 4.49) for AZA versus CYC, 0.32 (0.04, 2.25) for MMF versus CYC, 2.40 (0.22, 36.94) for prednisone alone versus CYC, and 0.45 (0.11, 1.48) for MMF versus AZA. The probability (95% credible interval) of developing renal failure at 2 years as expected for each agent was 6% (0.7%, 24%) for MMF, 12% (2%, 37%) for AZA, 16% (5%, 33%) for CYC, and 31% (5%, 81%) for prednisone alone. After applying a skeptical prior in the Bayesian analysis, there was no evidence of benefit for 1 therapy over another.
  
  
  CONCLUSIONS
  Although the data suggest that MMF may be superior to other treatments for the maintenance treatment of PLN, the evidence is not conclusive.
authors.affiliation: From the Institute of Medical Science, Department of Pediatrics, Institute of Health Policy, Management and Evaluation, and the Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, and the Hospital Library, The Hospital for Sick Children; Cancer Care Ontario, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.S.Y. Tian, MB, MSc, PhD (C), Institute of Medical Science, Faculty of Medicine, University of Toronto, and The Hospital for Sick Children; B.M. Feldman, MD, MSc, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Health Policy, Management and Evaluation, Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto; J. Beyene, PhD, Associate Professor, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; P.E. Brown, PhD, Associate Professor, Cancer Care Ontario, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University; E.M. Uleryk, MLS, Hospital Library, The Hospital for Sick Children; E.D. Silverman, MD, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto.
authors.forename: Simon Yu
authors.initials: SY
authors.lastname: Tian
authors.affiliation: From the Institute of Medical Science, Department of Pediatrics, Institute of Health Policy, Management and Evaluation, and the Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, and the Hospital Library, The Hospital for Sick Children; Cancer Care Ontario, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.S.Y. Tian, MB, MSc, PhD (C), Institute of Medical Science, Faculty of Medicine, University of Toronto, and The Hospital for Sick Children; B.M. Feldman, MD, MSc, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Health Policy, Management and Evaluation, Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto; J. Beyene, PhD, Associate Professor, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; P.E. Brown, PhD, Associate Professor, Cancer Care Ontario, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University; E.M. Uleryk, MLS, Hospital Library, The Hospital for Sick Children; E.D. Silverman, MD, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
authors.affiliation: From the Institute of Medical Science, Department of Pediatrics, Institute of Health Policy, Management and Evaluation, and the Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, and the Hospital Library, The Hospital for Sick Children; Cancer Care Ontario, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.S.Y. Tian, MB, MSc, PhD (C), Institute of Medical Science, Faculty of Medicine, University of Toronto, and The Hospital for Sick Children; B.M. Feldman, MD, MSc, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Health Policy, Management and Evaluation, Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto; J. Beyene, PhD, Associate Professor, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; P.E. Brown, PhD, Associate Professor, Cancer Care Ontario, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University; E.M. Uleryk, MLS, Hospital Library, The Hospital for Sick Children; E.D. Silverman, MD, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto.
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: From the Institute of Medical Science, Department of Pediatrics, Institute of Health Policy, Management and Evaluation, and the Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, and the Hospital Library, The Hospital for Sick Children; Cancer Care Ontario, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.S.Y. Tian, MB, MSc, PhD (C), Institute of Medical Science, Faculty of Medicine, University of Toronto, and The Hospital for Sick Children; B.M. Feldman, MD, MSc, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Health Policy, Management and Evaluation, Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto; J. Beyene, PhD, Associate Professor, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; P.E. Brown, PhD, Associate Professor, Cancer Care Ontario, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University; E.M. Uleryk, MLS, Hospital Library, The Hospital for Sick Children; E.D. Silverman, MD, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Brown
authors.affiliation: From the Institute of Medical Science, Department of Pediatrics, Institute of Health Policy, Management and Evaluation, and the Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, and the Hospital Library, The Hospital for Sick Children; Cancer Care Ontario, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.S.Y. Tian, MB, MSc, PhD (C), Institute of Medical Science, Faculty of Medicine, University of Toronto, and The Hospital for Sick Children; B.M. Feldman, MD, MSc, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Health Policy, Management and Evaluation, Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto; J. Beyene, PhD, Associate Professor, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; P.E. Brown, PhD, Associate Professor, Cancer Care Ontario, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University; E.M. Uleryk, MLS, Hospital Library, The Hospital for Sick Children; E.D. Silverman, MD, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Uleryk
authors.affiliation: From the Institute of Medical Science, Department of Pediatrics, Institute of Health Policy, Management and Evaluation, and the Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, and the Hospital Library, The Hospital for Sick Children; Cancer Care Ontario, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.S.Y. Tian, MB, MSc, PhD (C), Institute of Medical Science, Faculty of Medicine, University of Toronto, and The Hospital for Sick Children; B.M. Feldman, MD, MSc, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Health Policy, Management and Evaluation, Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto; J. Beyene, PhD, Associate Professor, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto; P.E. Brown, PhD, Associate Professor, Cancer Care Ontario, and Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University; E.M. Uleryk, MLS, Hospital Library, The Hospital for Sick Children; E.D. Silverman, MD, FRCPC, Professor, Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children, and Institute of Medical Science, Department of Pediatrics, Faculty of Medicine, University of Toronto. earl.silverman@sickkids.ca.
authors.forename: Earl D
authors.initials: ED
authors.lastname: Silverman
mesh_terms: D001379:Azathioprine / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008181:Lupus Nephritis / Q000188:drug therapy*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone
keywords: CLINICAL TRIALS; DRUG THERAPY; IMMUNOSUPPRESSIVE AGENTS; LUPUS NEPHRITIS; METAANALYSIS; SYSTEMIC LUPUS ERYTHEMATOSUS