Short-Term Effects of Rituximab in Children with Steroid-... : Clinical Journal of the American Society of Nephrology (original) (raw)

Original Articles: Original Articles

Short-Term Effects of Rituximab in Children with Steroid- and Calcineurin-Dependent Nephrotic Syndrome

A Randomized Controlled Trial

Ravani, Pietro*; Magnasco, Alberto†; Edefonti, Alberto‡; Murer, Luisa§; Rossi, Rossella*; Ghio, Luciana‡; Benetti, Elisa§; Scozzola, Floriana§; Pasini, Andrea‖; Dallera, Nadia¶; Sica, Felice**; Belingheri, Mirco‡; Scolari, Francesco¶; Ghiggeri, Gian Marco†

*Division of Nephrology, University of Calgary, Calgary, Alberta, Canada;

†Division of Nephrology, Dialysis, Transplantation and Pharmacology Section, Giannina Gaslini, Children Hospital, Genoa, Italy;

‡Pediatric Nephrology and Dialysis Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy;

§Pediatric Nephrology, Dialysis and Transplantation Unit, Azienda Ospedaliera-University of Padova, Padova, Italy;

‖Nephrology and Pediatric Dialysis, Department of Pediatrics, Azienda Ospedaliera Universitaria Sant'Orsola, Bologna, Italy;

¶Division of Nephrology and Dialysis, Ospedale di Montichiari, Brescia, Italy; and

**Division of Pediatrics, Hospital of Foggia, Foggia, Italy

Correspondence: Dr. Gian Marco Ghiggeri, Division of Nephrology, Dialysis and Transplantation and Laboratory on Pathophysiology of Uremia, Istituto G. Gaslini, Largo G. Gaslini 5, Genoa, Italy. Phone: (+39) 010 380742; Fax: (+39) 010 395214; E-mail: [email protected]

P.R. and A.M. contributed equally to this work.

Received October 20, 2010

Accepted February 9, 2011

Abstract

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/m2 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.