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Low-dose ofatumumab for rituximab-resistant nephrotic syndrome.

ABSTRACT: Drug resistant idiopathic nephrotic syndrome (DRNS) remains a therapeutic dilemma. In this pilot study, the efficacy of the new fully humanised, anti-CD20 monoclonal antibody ofatumumab was tested in 4 children with persistence of proteinuria for at least 12 months in spite of a full drug approach (including rituximab). We used a low-dose 2-infusion ofatumumab model (300+700 mg/1.73 m(2) 2 weeks apart) using specified premedication. Transient normalisation of proteinuria (persisting for 2 months) was achieved in 1 child while another presented stable remission after 12 months; both had normal renal function. The outcome was not modified in the remaining 2 children presenting an impaired renal function. These results demonstrate that low-dose ofatumumab may induce remittance of proteinuria in children with a long story of DRNS and normal renal function. Further studies are needed to test whether higher doses of ofatumumab can also modify proteinuria in patients with impaired renal function.

SUBMITTER: Bonanni A

PROVIDER: S-EPMC4577716 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Low-dose ofatumumab for rituximab-resistant nephrotic syndrome.

Bonanni Alice A Rossi Roberta R Murtas Corrado C Ghiggeri Gian Marco GM

BMJ case reports 20150916

Drug resistant idiopathic nephrotic syndrome (DRNS) remains a therapeutic dilemma. In this pilot study, the efficacy of the new fully humanised, anti-CD20 monoclonal antibody ofatumumab was tested in 4 children with persistence of proteinuria for at least 12 months in spite of a full drug approach (including rituximab). We used a low-dose 2-infusion ofatumumab model (300+700 mg/1.73 m(2) 2 weeks apart) using specified premedication. Transient normalisation of proteinuria (persisting for 2 months ...[more]

PMID: 26376698

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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

Low-dose ofatumumab for rituximab-resistant nephrotic syndrome.

Publications

Low-dose ofatumumab for rituximab-resistant nephrotic syndrome.

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