title: Induction and Maintenance Immunosuppression Treatment of Proliferative Lupus Nephritis: A Network Meta-analysis of Randomized Trials.
abstract: BACKGROUND
  Intravenous (IV) cyclophosphamide has been first-line treatment for inducing disease remission in lupus nephritis. The comparative efficacy and toxicity of newer agents such as mycophenolate mofetil (MMF) and calcineurin inhibitors are uncertain.
  
  
  METHODS
  Network meta-analysis.
  
  
  METHODS
  Patients with proliferative lupus nephritis.
  
  
  METHODS
  Randomized trials of immunosuppression to induce or maintain disease remission.
  
  
  METHODS
  IV cyclophosphamide, oral cyclophosphamide, MMF, calcineurin inhibitor, plasma exchange, rituximab, or azathioprine, alone or in combination.
  
  
  RESULTS
  Complete remission, end-stage kidney disease, all-cause mortality, doubling of serum creatinine level, relapse, and adverse events.
  
  
  RESULTS
  53 studies involving 4,222 participants were eligible. Induction and maintenance treatments were administered for 12 (IQR, 6-84) and 25 (IQR, 12-48) months, respectively. There was no evidence of different effects between therapies on all-cause mortality, doubling of serum creatinine level, or end-stage kidney disease. Compared to IV cyclophosphamide, the most effective treatments to induce remission in moderate- to high-quality evidence were combined MMF and calcineurin inhibitor therapy, calcineurin inhibitors, and MMF (ORs were 2.69 [95% CI, 1.74-4.16], 1.86 [95% CI, 1.05-3.30], and 1.54 [95% CI, 1.04-2.30], respectively). MMF was significantly less likely than IV cyclophosphamide to cause alopecia (OR, 0.21; 95% CI, 0.12-0.36), and MMF combined with calcineurin inhibitor therapy was less likely to cause ovarian failure (OR, 0.25; 95% CI, 0.07-0.93). Regimens generally had similar odds of major infection. MMF was the most effective strategy to maintain remission.
  
  
  CONCLUSIONS
  Outcome definitions not standardized, short duration of follow-up, and possible confounding by previous or subsequent therapy.
  
  
  CONCLUSIONS
  Evidence for induction therapy for lupus nephritis is inconclusive based on treatment effects on all-cause mortality, doubling of serum creatinine level, and end-stage kidney disease. MMF, calcineurin inhibitors, or their combination were most effective for inducing remission compared to IV cyclophosphamide, while conferring similar or lower treatment toxicity. MMF was the most effective maintenance therapy.
authors.affiliation: Department of Medicine, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Suetonia C
authors.initials: SC
authors.lastname: Palmer
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tunnicliffe
authors.affiliation: School of Paediatrics and Child Health, The University of Sydney, Sydney, NSW, Australia; Department of Rheumatology, The Sydney Children's Hospitals Network Westmead and Randwick, NSW, Australia.
authors.forename: Davinder
authors.initials: D
authors.lastname: Singh-Grewal
authors.affiliation: Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Department of Primary Education, University of Ioannina, Ioannina, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Mavridis
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, Canada.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tonelli
authors.affiliation: Division of Medicine, Department of Nephrology, University of Queensland at the Princess Alexandra Hospital, Brisbane, QLD, Australia; Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, NSW, Australia.
authors.forename: Allison
authors.initials: A
authors.lastname: Tong
authors.affiliation: Sydney School of Public Health, University of Sydney, Sydney, NSW, Australia; Diaverum Medical Scientific Office and Diaverum Academy, Lund, Sweden; Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy. Electronic address: gfmstrippoli@gmail.com.
authors.forename: Giovanni F M
authors.initials: GFM
authors.lastname: Strippoli
mesh_terms: D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008181:Lupus Nephritis / Q000276:immunology / Q000628:therapy; D016032:Randomized Controlled Trials as Topic; D012074:Remission Induction / Q000379:methods; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents
keywords: Lupus nephritis; adverse events; calcineurin inhibitor; dialysis; end-stage kidney disease (ESKD); immunosuppression; induction therapy; intravenous cyclophosphamide; maintenance therapy; meta-analysis; mycophenolate mofetil (MMF); remission; renal failure; toxicity