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

ABSTRACT: 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 Oral agents were tapered after each infusion, and completely withdrawn within 45 days.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.

SUBMITTER: Ravani P

PROVIDER: S-EPMC3816123 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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

Ravani Pietro P Ponticelli Alessandro A Siciliano Chiara C Fornoni Alessia A Magnasco Alberto A Sica Felice F Bodria Monica M Caridi Gianluca G Wei Changli C Belingheri Mirco M Ghio Luciana L Merscher-Gomez Sandra S Edefonti Alberto A Pasini Andrea A Montini Giovanni G Murtas Corrado C Wang Xiangyu X Muruve Daniel D Vaglio Augusto A Martorana Davide D Pani Antonello A Scolari Francesco F Reiser Jochen J Ghiggeri Gian M GM

Kidney international 20130605 5

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 ...[more]

PMID: 23739238

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Project description:IntroductionOral steroids induce remission in about 90% of children with idiopathic nephrotic syndrome (INS), which is characterised by severe proteinuria and hypoalbuminaemia. Some children become steroid-dependent (SD) and require addition of calcineurin inhibitors (CNI) to maintain remission. Since these oral agents are toxic, alternative interventions are needed for long-term treatment. The anti-CD20 antibody rituximab has shown promising steroid-sparing properties in clinical trials, but benefits are less convincing in complicated forms of SD-INS. Ofatumumab, a new anti-CD20 antibody with stronger affinity to CD20, may be superior to rituximab in maintaining oral steroid-free and CNI-free disease remission in children with SD-INS.Methods and analysisThis open-label, two-parallel-arm, controlled, phase II randomised clinical trial will enrol children with SD-INS maintained in remission with oral steroids and CNI. Children will be randomised to either ofatumumab or rituximab infusion. After infusion of either antibody, steroids will be maintained for 30 days and then tapered off by 0.3 mg/kg/week until complete withdrawal. 1 week after complete steroid withdrawal, CNI will be decreased by 50% and withdrawn within 2 additional weeks. We will enrol 140 children to detect as significant at the 2-sided p value of 0.01 with a power of >0.8, a reduction in the risk of 1-year relapse (primary end point) of at least 0.3 (ie, from 0.65 to 0.35; (risk ratio 0.54)) in the ofatumumab arm when compared with the rituximab arm. We will compare the amount of steroids required to maintain complete disease remission at 6 and 24 months, relapse-free period, relapse rate per year as secondary end points. Circulating cell populations will be studied as biomarkers or predictors of the anti-CD20 response.Ethics and disseminationThe trial received ethics approval from the local ethics board. We will publish study results and present them at international scientific meetings.Trial registration numbersNCT02394119; 2015-000624-28; Pre-results.

Dataset Information

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

Publications

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

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