title: Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial.
abstract: Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, noninferiority, randomized controlled trial at four sites in Italy tested whether rituximab is noninferior to steroids in maintaining remission in juvenile SDNS. We enrolled children age 1-16 years who had developed SDNS in the previous 6-12 months and were maintained in remission with high prednisone doses (≥0.7 mg/kg per day). We randomly assigned participants to continue prednisone alone for 1 month (control) or to add a single intravenous infusion of rituximab (375 mg/m(2); intervention). Prednisone was tapered in both groups after 1 month. For noninferiority, rituximab had to permit steroid withdrawal and maintain 3-month proteinuria (mg/m(2) per day) within a prespecified noninferiority margin of three times the levels among controls (primary outcome). We followed participants for ≥1 year to compare risk of relapse (secondary outcome). Fifteen children per group (21 boys; mean age, 7 years [range, 2.6-13.5 years]) were enrolled and followed for ≤60 months (median, 22 months). Three-month proteinuria was 42% lower in the rituximab group (geometric mean ratio, 0.58; 95% confidence interval, 0.18 to 1.95 [i.e., within the noninferiority margin of three times the levels in controls]). All but one child in the control group relapsed within 6 months; median time to relapse in the rituximab group was 18 months (95% confidence interval, 9 to 32 months). In the rituximab group, nausea and skin rash during infusion were common; transient acute arthritis occurred in one child. In conclusion, rituximab was noninferior to steroids for the treatment of juvenile SDNS.
authors.affiliation: Division of Nephrology, University of Calgary, Calgary, Alberta, Canada; GMarcoGhiggeri@ospedale-gaslini.ge.it pravani@ucalgary.ca.
authors.forename: Pietro
authors.initials: P
authors.lastname: Ravani
authors.affiliation: Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy;
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy;
authors.forename: Alice
authors.initials: A
authors.lastname: Bonanni
authors.affiliation: Division of Nephrology, University of Calgary, Calgary, Alberta, Canada;
authors.forename: Robert R
authors.initials: RR
authors.lastname: Quinn
authors.affiliation: Division of Pediatrics, Hospital of Foggia, Foggia, Italy;
authors.forename: Felice
authors.initials: F
authors.lastname: Sica
authors.affiliation: Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy;
authors.forename: Monica
authors.initials: M
authors.lastname: Bodria
authors.affiliation: Nephrology and Pediatric Dialysis, Department of Pediatrics, Azienda Ospedaliera Universitaria Sant'Orsola, Bologna, Italy;
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.affiliation: Nephrology and Pediatric Dialysis, Department of Pediatrics, Azienda Ospedaliera Universitaria Sant'Orsola, Bologna, Italy;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montini
authors.affiliation: Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy;
authors.forename: Alberto
authors.initials: A
authors.lastname: Edefonti
authors.affiliation: Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy;
authors.forename: Mirco
authors.initials: M
authors.lastname: Belingheri
authors.affiliation: Division of Pediatrics, Hospital of Foggia, Foggia, Italy;
authors.forename: Donatella
authors.initials: D
authors.lastname: De Giovanni
authors.affiliation: Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy;
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Barbano
authors.affiliation: Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy;
authors.forename: Ludovica
authors.initials: L
authors.lastname: Degl'Innocenti
authors.affiliation: Division of Nephrology and Dialysis, Ospedale di Montichiari Azienda Ospedaliera Spedali Civili di Brescia, Brescia, Italy;
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.affiliation: Pediatric Nephrology, Dialysis and Transplant Unit, Department of Pediatrics, University Hospital of Padua, Padua, Italy;
authors.forename: Luisa
authors.initials: L
authors.lastname: Murer
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, Illinois; and.
authors.forename: Jochen
authors.initials: J
authors.lastname: Reiser
authors.affiliation: Miller School of Medicine, University of Miami, Miami, Florida.
authors.forename: Alessia
authors.initials: A
authors.lastname: Fornoni
authors.affiliation: Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Genoa, Italy;
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects*; D011507:Proteinuria / Q000209:etiology; D012008:Recurrence; D000069283:Rituximab / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D000069283:Rituximab; D011241:Prednisone
keywords: nephrotic syndrome; primary glomerulonephritis; randomized controlled trials