title: Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial.
abstract: OBJECTIVE
  Prednisone and calcineurin inhibitors are the mainstay therapy of idiopathic nephrotic syndrome (INS) in children. However, drug dependence and toxicity associated with protracted use are common. Case series suggest that the anti-CD20 monoclonal antibody rituximab (RTX) may maintain disease remission.
  
  
  METHODS
  This open-label randomized controlled trial was powered to show that a strategy based on RTX and lower doses of prednisone and calcineurin inhibitors was noninferior to standard doses of these agents in maintaining 3-month proteinuria as low as baseline or up to 1 g/d greater (noninferiority margin). Participants were stratified by the presence of toxicity to prednisone/calcineurin inhibitors and centrally assigned to add RTX (Mabthera, 375 mg/m(2) intravenously) to lower doses of standard agents or to continue with current therapy alone. The risk of relapse was a secondary outcome.
  
  
  RESULTS
  Fifty-four children (mean age 11 ± 4 years) with INS dependent on prednisone and calcineurin inhibitors for >12 months were randomized. Three-month proteinuria was 70% lower in the RTX arm (95% confidence interval 35% to 86%) as compared with standard therapy arm (intention-to-treat); relapse rates were 18.5% (intervention) and 48.1% (standard arm) (P = 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P < 0.001); 50% of RTX cases were in stable remission without drugs after 9 months.
  
  
  CONCLUSIONS
  Rituximab and lower doses of prednisone and calcineurin inhibitors are noninferior to standard therapy in maintaining short-term remission in children with INS dependent on both drugs and allow their temporary withdrawal.
authors.affiliation: Division of Nephrology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.forename: Alberto
authors.initials: A
authors.lastname: Magnasco
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.forename: Rossella
authors.initials: R
authors.lastname: Rossi
authors.forename: Luciana
authors.initials: L
authors.lastname: Ghio
authors.forename: Elisa
authors.initials: E
authors.lastname: Benetti
authors.forename: Floriana
authors.initials: F
authors.lastname: Scozzola
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.forename: Nadia
authors.initials: N
authors.lastname: Dallera
authors.forename: Felice
authors.initials: F
authors.lastname: Sica
authors.forename: Mirco
authors.initials: M
authors.lastname: Belingheri
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002648:Child; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007558:Italy; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000201:enzymology; D016017:Odds Ratio; D011507:Proteinuria / Q000188:drug therapy / Q000201:enzymology; D012008:Recurrence; D012074:Remission Induction; D018570:Risk Assessment; D012307:Risk Factors; D000069283:Rituximab; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D013256:Steroids; D000069283:Rituximab; D019703:Calcineurin