Journal Article

Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor–dependent idiopathic nephrotic syndrome

Edefonti, Alberto, Montini, Giovanni, Wang, Xiangyu, Reiser, Jochen, Wei, Changli, Merscher-Gomez, Sandra, Pani, Antonello, Ponticelli, Alessandro, Sica, Felice, Muruve, Daniel, Siciliano, Chiara, Martorana, Davide, Bodria, Monica, Fornoni, Alessia, Vaglio, Augusto, Magnasco, Alberto, Belingheri, Mirco, Murtas, Corrado, Scolari, Francesco, Caridi, Gianluca, Ghiggeri, Gian M., Ravani, Pietro, Ghio, Luciana, Pasini, Andrea

2013

Overview

In children with idiopathic nephrotic syndrome, rituximab can maintain short-term remission with withdrawal of prednisone and calcineurin inhibitors. Long-term effects including the number of repeated infusions to maintain remission are unknown. To test this, we treated 46 consecutive children with idiopathic nephrotic syndrome lasting for at least 1 year (mean 6.3 years), maintained in remission with oral prednisone and calcineurin inhibitors. They received 1–5 rituximab courses during a median follow-up of 3 years. Oral agents were tapered after each infusion, and completely withdrawn within 45 days. Rituximab was well tolerated. Six-month probabilities of remission were 48% after the first infusion and 37% after subsequent infusions. One- and 2-year-remission probabilities were, respectively, 20 and 10%. Median time intervals between complete oral-agent withdrawal and relapse were 5.6 and 8.5 months, respectively, following the first and subsequent courses. The time to reconstitution of CD20 cells correlated with the duration of remission, but was not associated with variation in FcyR, CD20, or SMPDL-3B polymorphisms. Podocyte Src phosphorylation was normal. Thus, rituximab can be safely and repeatedly used as a prednisone and calcineurin inhibitor–sparing therapy in a considerable proportion of children with dependent forms of idiopathic nephrotic syndrome. Further study is needed to identify patients who will benefit most from rituximab therapy.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Administration, Oral / Adolescent / Age Factors / Antibodies, Monoclonal, Murine-Derived - administration & dosage / Antibodies, Monoclonal, Murine-Derived - adverse effects / Antibodies, Monoclonal, Murine-Derived - therapeutic use / Antigens, CD20 - genetics / Antigens, CD20 - metabolism / Calcineurin - metabolism / Calcineurin Inhibitors / Child / Child, Preschool / clinical trial / Drug Administration Schedule / Female / Glucocorticoids - administration & dosage / Glucocorticoids - adverse effects / Glucocorticoids - therapeutic use / Humans / Immunosuppressive Agents - administration & dosage / Immunosuppressive Agents - adverse effects / Immunosuppressive Agents - therapeutic use / Infusions, Intravenous / Kaplan-Meier Estimate / Kidney - drug effects / Kidney - immunology / Kidney - metabolism / Male / nephrotic syndrome / Nephrotic Syndrome - diagnosis / Nephrotic Syndrome - drug therapy / Nephrotic Syndrome - genetics / Nephrotic Syndrome - immunology / pediatrics / Phosphorylation / Podocytes - drug effects / Podocytes - immunology / Podocytes - metabolism / Polymorphism, Genetic / Prednisone - administration & dosage / Prednisone - adverse effects / Prednisone - therapeutic use / Prospective Studies / proteinuria / Receptors, IgG - genetics / Recurrence / Remission Induction / Risk Factors / Rituximab / Sphingomyelin Phosphodiesterase - genetics / src-Family Kinases - metabolism / Time Factors / Treatment Outcome