title: Immunosuppressive therapies for the induction treatment of proliferative lupus nephritis: a systematic review and network metaanalysis.
abstract: OBJECTIVE
  To evaluate and determine the most effective immunosuppressive therapy for the induction treatment of proliferative lupus nephritis (PLN) based on renal remission.
  
  
  METHODS
  A systematic review of randomized controlled trials was conducted. The outcomes were renal remission at 6 months: (1) normalization of serum creatinine [(sCr), or within 15% of the normal range, i.e., sCr < 132 µmol/l - creatinine remission]; and (2) proteinuric remission (prU < 0.5 g/day/1.73m(2)). A Bayesian network metaanalysis was used.
  
  
  RESULTS
  The OR (95% credible interval) of inducing an sCr remission at 6 months was 1.70 (0.51, 6.87) for mycophenolate mofetil (MMF) versus cyclophosphamide (CYC); 2.16 (0.38, 13.36) for tacrolimus (Tac) versus CYC; and 1.25 (0.13, 10.51) for Tac versus MMF. For proteinuric remission the OR was 1.46 (0.81, 3.04) for MMF versus CYC; 1.96 (0.80, 5.11) for Tac versus CYC; and 1.34 (0.43, 3.90) for Tac versus MMF. The probability (95% credible interval) of inducing a creatinine remission at 6 months was Tac 56% (19%, 88%); MMF 51% (23%, 79%); and CYC 37% (28%, 47%). The probability of inducing a proteinuric remission was Tac 41% (23%, 63%); MMF 34% (23%, 50%); CYC 26% (20%, 32%); azathioprine 10% (1%, 55%); prednisone 11% (2%, 38%). None of the results were conclusive when examined in a sensitivity analysis.
  
  
  CONCLUSIONS
  There is currently insufficient evidence to determine which of these immunosuppressive agents is superior. The probability of renal remission is 50% or lower at 6 months.
authors.affiliation: From the Institute of Medical Science, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children; Department of Pediatrics, Faculty of Medicine, University of Toronto; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton; Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto; Cancer Care Ontario, Toronto; Hospital Library, The Hospital for Sick Children, Toronto, Ontario, Canada.S.Y. Tian's PhD research is funded in part by the Queen Elizabeth II-Edward Dunlop Foundation Scholarships in Science and Technology, administered at the University of Toronto.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, Institute of Health Policy, Management and Evaluation, University of Toronto, and The Hospital for Sick Children; 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, and Department of Immunology, Univer
authors.forename: Simon Yu
authors.initials: SY
authors.lastname: Tian
authors.affiliation: From the Institute of Medical Science, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children; Department of Pediatrics, Faculty of Medicine, University of Toronto; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton; Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto; Cancer Care Ontario, Toronto; Hospital Library, The Hospital for Sick Children, Toronto, Ontario, Canada.S.Y. Tian's PhD research is funded in part by the Queen Elizabeth II-Edward Dunlop Foundation Scholarships in Science and Technology, administered at the University of Toronto.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, Institute of Health Policy, Management and Evaluation, University of Toronto, and The Hospital for Sick Children; 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, and Department of Immunology, Univer
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
authors.affiliation: From the Institute of Medical Science, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children; Department of Pediatrics, Faculty of Medicine, University of Toronto; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton; Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto; Cancer Care Ontario, Toronto; Hospital Library, The Hospital for Sick Children, Toronto, Ontario, Canada.S.Y. Tian's PhD research is funded in part by the Queen Elizabeth II-Edward Dunlop Foundation Scholarships in Science and Technology, administered at the University of Toronto.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, Institute of Health Policy, Management and Evaluation, University of Toronto, and The Hospital for Sick Children; 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, and Department of Immunology, Univer
authors.forename: Joseph
authors.initials: J
authors.lastname: Beyene
authors.affiliation: From the Institute of Medical Science, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children; Department of Pediatrics, Faculty of Medicine, University of Toronto; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton; Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto; Cancer Care Ontario, Toronto; Hospital Library, The Hospital for Sick Children, Toronto, Ontario, Canada.S.Y. Tian's PhD research is funded in part by the Queen Elizabeth II-Edward Dunlop Foundation Scholarships in Science and Technology, administered at the University of Toronto.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, Institute of Health Policy, Management and Evaluation, University of Toronto, and The Hospital for Sick Children; 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, and Department of Immunology, Univer
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Brown
authors.affiliation: From the Institute of Medical Science, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children; Department of Pediatrics, Faculty of Medicine, University of Toronto; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton; Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto; Cancer Care Ontario, Toronto; Hospital Library, The Hospital for Sick Children, Toronto, Ontario, Canada.S.Y. Tian's PhD research is funded in part by the Queen Elizabeth II-Edward Dunlop Foundation Scholarships in Science and Technology, administered at the University of Toronto.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, Institute of Health Policy, Management and Evaluation, University of Toronto, and The Hospital for Sick Children; 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, and Department of Immunology, Univer
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Uleryk
authors.affiliation: From the Institute of Medical Science, Faculty of Medicine, University of Toronto; Division of Rheumatology and Program of Child Health Evaluative Sciences, The Hospital for Sick Children; Department of Pediatrics, Faculty of Medicine, University of Toronto; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto; Program in Population Genomics, Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton; Dalla Lana School of Public Health, Faculty of Medicine, University of Toronto, Toronto; Cancer Care Ontario, Toronto; Hospital Library, The Hospital for Sick Children, Toronto, Ontario, Canada.S.Y. Tian's PhD research is funded in part by the Queen Elizabeth II-Edward Dunlop Foundation Scholarships in Science and Technology, administered at the University of Toronto.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, Institute of Health Policy, Management and Evaluation, University of Toronto, and The Hospital for Sick Children; 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, and Department of Immunology, Univer
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 / Q000379:methods*; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone; D016559:Tacrolimus
keywords: CLINICAL TRIALS; DRUG THERAPY; IMMUNOSUPPRESSIVE AGENTS; LUPUS NEPHRITIS; METAANALYSIS; SYSTEMIC LUPUS ERYTHEMATOSUS