title: A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).
abstract: BACKGROUND
  Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria.
  
  
  METHODS
  Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study.
  
  
  CONCLUSIONS
  This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.
authors.affiliation: Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minn., USA.
authors.forename: Fernando C
authors.initials: FC
authors.lastname: Fervenza
authors.forename: Pietro A
authors.initials: PA
authors.lastname: Canetta
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Barbour
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lafayette
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.forename: Nabeel
authors.initials: N
authors.lastname: Aslam
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hladunewich
authors.forename: Maria V
authors.initials: MV
authors.lastname: Irazabal
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Sethi
authors.forename: Debbie S
authors.initials: DS
authors.lastname: Gipson
authors.forename: Heather N
authors.initials: HN
authors.lastname: Reich
authors.forename: Paul
authors.initials: P
authors.lastname: Brenchley
authors.forename: Matthias
authors.initials: M
authors.lastname: Kretzler
authors.forename: Jai
authors.initials: J
authors.lastname: Radhakrishnan
authors.forename: Lee A
authors.initials: LA
authors.lastname: Hebert
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Gipson
authors.forename: Leslie F
authors.initials: LF
authors.lastname: Thomas
authors.forename: Ellen T
authors.initials: ET
authors.lastname: McCarthy
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Appel
authors.forename: J Ashley
authors.initials: JA
authors.lastname: Jefferson
authors.forename: Alfonso
authors.initials: A
authors.lastname: Eirin
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hogan
authors.forename: Eddie L
authors.initials: EL
authors.lastname: Greene
authors.forename: John J
authors.initials: JJ
authors.lastname: Dillon
authors.forename: Nelson
authors.initials: N
authors.lastname: Leung
authors.forename: John R
authors.initials: JR
authors.lastname: Sedor
authors.forename: Dana V
authors.initials: DV
authors.lastname: Rizk
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Blumenthal
authors.forename: Lada B
authors.initials: LB
authors.lastname: Lasic
authors.forename: Luis A
authors.initials: LA
authors.lastname: Juncos
authors.forename: Dollie F
authors.initials: DF
authors.lastname: Green
authors.forename: James
authors.initials: J
authors.lastname: Simon
authors.forename: Amy N
authors.initials: AN
authors.lastname: Sussman
authors.forename: David
authors.initials: D
authors.lastname: Philibert
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Cattran
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D023381:Endpoint Determination; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D011507:Proteinuria / Q000188:drug therapy; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007166:Immunosuppressive Agents; D000069283:Rituximab; D016572:Cyclosporine