Pietro Ravani1, Francesca Lugani2, Isabella Pisani3, Monica Bodria2, Giorgio Piaggio2, Domenico Bartolomeo3, Marco Prunotto4, Gian Marco Ghiggeri5. 1. Division of Nephrology, Faculty of Medicine, Foothills Medical Centre, University of Calgary, 1403-29th Street NW, Calgary, AB, T2N 2T9, Canada. pravani@ucalgary.ca. 2. Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Via Gerolamo Gaslini 5, 16148, Genoa, Italy. 3. Department of Medicine and Surgery, Division of Nephrology, School of Nephrology, University of Parma, Parma, Italy. 4. School of Pharmaceutical Sciences, University of Geneva, Geneva, Switzerland. 5. Division of Nephrology, Dialysis, Transplantation, Giannina Gaslini Children's Hospital, Via Gerolamo Gaslini 5, 16148, Genoa, Italy. GMarcoGhiggeri@ospedale-gaslini.ge.it.
Abstract
BACKGROUND: Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, randomized controlled trial was designed to test whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS and how long remission may last (EudraCT:2008-004486-26). METHODS: We enrolled 30 children 4-15 years who had developed SDNS 6-12 months before and were maintained in remission with low prednisone doses (0.1-0.4 mg/Kg/day). Participants were randomized following a non-inferiority design to continue prednisone alone (n 15, controls) or to add a single intravenous infusion of rituximab (375 mg/m2, n 15 intervention). Prednisone was tapered in both arms after 1 month. Children assigned to the control arm were allowed to receive rituximab to treat disease relapse. RESULTS:Proteinuria increased at 3 months in the prednisone group (from 0.14 to 1.5 g/day) (p < 0.001) and remained unchanged in the rituximab group (0.14 g/day). Fourteen children in the control arm relapsed within 6 months. Thirteen children assigned torituximab (87%) were still in remission at 1 year and 8 (53%) at 4 years. Responses were similar in children of the control group who received rituximab to treat disease relapse. We did not record significant adverse events. CONCLUSIONS:Rituximab was non-inferior to steroids for the treatment of juvenile SDNS. One in two children remains in remission at 4 years following a single infusion of rituximab, without significant adverse events. Further studies are needed to clarify the superiority of rituximab over low-dose corticosteroid as a treatment of SDNS.
RCT Entities:
BACKGROUND:Steroid-dependent nephrotic syndrome (SDNS) carries a high risk of toxicity from steroids or steroid-sparing agents. This open-label, randomized controlled trial was designed to test whether the monoclonal antibody rituximab is non-inferior to steroids in maintaining remission in juvenile forms of SDNS and how long remission may last (EudraCT:2008-004486-26). METHODS: We enrolled 30 children 4-15 years who had developed SDNS 6-12 months before and were maintained in remission with low prednisone doses (0.1-0.4 mg/Kg/day). Participants were randomized following a non-inferiority design to continue prednisone alone (n 15, controls) or to add a single intravenous infusion of rituximab (375 mg/m2, n 15 intervention). Prednisone was tapered in both arms after 1 month. Children assigned to the control arm were allowed to receive rituximab to treat disease relapse. RESULTS:Proteinuria increased at 3 months in the prednisone group (from 0.14 to 1.5 g/day) (p < 0.001) and remained unchanged in the rituximab group (0.14 g/day). Fourteen children in the control arm relapsed within 6 months. Thirteen children assigned to rituximab (87%) were still in remission at 1 year and 8 (53%) at 4 years. Responses were similar in children of the control group who received rituximab to treat disease relapse. We did not record significant adverse events. CONCLUSIONS:Rituximab was non-inferior to steroids for the treatment of juvenile SDNS. One in two children remains in remission at 4 years following a single infusion of rituximab, without significant adverse events. Further studies are needed to clarify the superiority of rituximab over low-dose corticosteroid as a treatment of SDNS.
Authors: Pietro Ravani; Manuela Colucci; Maurizio Bruschi; Marina Vivarelli; Michela Cioni; Armando DiDonato; Paolo Cravedi; Francesca Lugani; Francesca Antonini; Marco Prunotto; Francesco Emma; Andrea Angeletti; Gian Marco Ghiggeri Journal: J Am Soc Nephrol Date: 2021-09-20 Impact factor: 14.978
Authors: Francesca Lugani; Andrea Angeletti; Pietro Ravani; Marina Vivarelli; Manuela Colucci; Gianluca Caridi; Enrico Verrina; Francesco Emma; Gian Marco Ghiggeri Journal: BMJ Open Date: 2021-11-29 Impact factor: 2.692
Authors: Rasmus Ehren; Marcus R Benz; Paul T Brinkkötter; Jörg Dötsch; Wolfgang R Eberl; Jutta Gellermann; Peter F Hoyer; Isabelle Jordans; Clemens Kamrath; Markus J Kemper; Kay Latta; Dominik Müller; Jun Oh; Burkhard Tönshoff; Stefanie Weber; Lutz T Weber Journal: Pediatr Nephrol Date: 2021-06-05 Impact factor: 3.714