1. Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome
- Author
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Francesco Scolari, Rossella Rossi, Luisa Murer, Alberto Edefonti, Alberto Magnasco, Gian Marco Ghiggeri, Mirco Belingheri, Floriana Scozzola, Pietro Ravani, Andrea Pasini, Felice Sica, Elisa Benetti, Luciana Ghio, and Nadia Dallera
- Subjects
Male ,Nephrotic Syndrome ,Time Factors ,Epidemiology ,Kaplan-Meier Estimate ,Critical Care and Intensive Care Medicine ,Gastroenterology ,law.invention ,Antibodies, Monoclonal, Murine-Derived ,Randomized controlled trial ,Recurrence ,Risk Factors ,Prednisone ,law ,Odds Ratio ,Medicine ,Enzyme Inhibitors ,Child ,Proteinuria ,Calcineurin ,Remission Induction ,Treatment Outcome ,Italy ,Nephrology ,Toxicity ,Drug Therapy, Combination ,Female ,Steroids ,Rituximab ,medicine.symptom ,Immunosuppressive Agents ,medicine.drug ,medicine.medical_specialty ,Adolescent ,Calcineurin Inhibitors ,Risk Assessment ,Drug Administration Schedule ,Pharmacotherapy ,Internal medicine ,Humans ,Transplantation ,business.industry ,Original Articles ,medicine.disease ,Logistic Models ,Immunology ,business ,Nephrotic syndrome - Abstract
Summary Background and objectives 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. Design, setting, participants, & measurements 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. Clin J Am Soc Nephrol 6: 1308–1315, 2011. doi: 10.2215/CJN.09421010
- Published
- 2011