Efficacy and safety of rituximab treatment in children with primary glomerulonephritis

Zachwieja, Jacek; Silska, Magdalena; Ostalska‐Nowicka, Danuta; Sołtysiak, Jolanta; Lipkowska, Katarzyna; Blumczynski, Andrzej; Musielak, Anna

doi:10.5301/jn.5000096

Cited by 10 publications

(6 citation statements)

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“…A previous publication explored the pharmacokinetics of RTX (administered as a 375 mg/m 2 dose) in children with nephrotic syndrome. 23 The authors reported a half-life (14.6 ± 5.2 days) similar to that in the current study. However, the exposures (83.2 ± 53.1 mg h/mL) and volume (2.2 ± 0.37 L/m 2 ) were greater, and clearance (5.83 ± 2.97 mL/h/m 2 ) values were lower in the pediatric study.…”

Section: Discussionsupporting

confidence: 88%

“…These pharmacokinetic outcomes indicate that MN patients have lower than expected exposures to RTX administered at the same doses as other populations. A previous publication explored the pharmacokinetics of RTX (administered as a 375 mg/m 2 dose) in children with nephrotic syndrome (23). The authors reported a similar half-life (14.6 ± 5.2 days) to the current study.…”

Section: Discussionsupporting

confidence: 74%

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Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy

et al. 2018

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Background: Rituximab (RTX) is a chimeric monoclonal anti-CD20 antibody used off-label in the treatment of membranous nephropathy (MN). Unfortunately, limited information is available on the pharmacokinetics of therapeutic proteins such as RTX in patients with glomerular kidney diseases. Objective: The current study evaluated RTX pharmacokinetics in patients with MN (n=20) who received 4 RTX weekly intravenous infusions (375 mg/m 2) over a month, with a repeat of the identical treatment at 6 months. Baseline patient characteristics were gender (17M/3F), age (49±13 years), and body surface area (2.2±0.24 m 2). Methods: Compartmental pharmacokinetic analyses were conducted using Phoenix® and comparisons of these parameters were made between the MN patients and published data from two reference populations without kidney diseases (follicular lymphoma and autoimmune disorders). Results: Patients with MN exhibited a shorter half-life, reduced volume of central compartment, decreased area under the serum concentration-time curve (exposure), and increased RTX clearance from central compartment vs. previous reports in the reference patient populations. Conclusions and Relevance: These results suggest that shorter half-life and lower exposures to RTX in patients with MN may necessitate higher doses and/or changes to dosing frequency in order to optimize the relationships between serum concentrations and therapeutic effects.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 74%

Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy

et al. 2018

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“…In patients with steroid‐dependent nephrotic syndrome (SDNS) or/and steroid‐resistant nephrotic syndrome (SRNS), immunosuppressive therapy with cyclophosphamide, mycophenolate mofetil or calcineurin inhibitors is used in order to induce or sustain remission . However, due to the many potential adverse events or/and the lack of satisfactory results, the search for alternative ways of the treatment, like monoclonal antibodies, continues . However, the problem of their administration, effectiveness and safety remains an open issue.…”

Section: Introductionmentioning

confidence: 99%

Multicenter analysis of the efficacy and safety of a non‐standard immunosuppressive therapy with rituximab in children with steroid‐resistant nephrotic syndrome

Zachwieja

Silska-Dittmar

Zurowska

et al. 2018

Clin Exp Pharma Physio

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The aim of the study was a multicenter analysis of the efficacy and safety of a nonstandard immunosuppressive therapy with rituximab (Rtx) in children with steroidresistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m 2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants. K E Y W O R D Scyclosporine A, glomerulonephritis, glucocorticoids, nephrology, paediatrics

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“…The efficacy of rituximab in patients with steroidresistant nephrotic syndrome (SRNS), however, seemed to be more dismal (4,8,(13)(14)(15). In an open label, randomized trial comparing rituximab therapy with steroids and CNI in 31 patients with SRNS, including 19 with FSGS, no demonstrable benefit was seen in patients treated with rituximab (15).…”

Section: Introductionmentioning

confidence: 99%

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS

Chan

Liu

Resontoc

et al. 2016

CJASN

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Background and objectives Rituximab is used with variable success in difficult FSGS. Because B cell depletion significantly affects T cell function, we characterized T cell subsets in patients with FSGS to determine if an immunologic signature predictive of favorable response to rituximab could be identified.Design, setting, participants, & measurements Twenty-two consecutive patients with FSGS (median age =14.4 years old; range =6.2-25.0 years old) and age of onset of nephrotic syndrome 1-18 years old receiving rituximab for clinical indications between October of 2009 and February of 2014 were studied. Indications for rituximab were lack of sustained remission despite calcineurin inhibitors (CNIs) and mycophenolate in steroid-resistant patients and lack of steroid-sparing effect with cyclophosphamide and CNI or CNI toxicity in steroid-dependent patients. Exclusion criteria were infantile onset, known genetic mutations, and secondary causes. Rituximab (375 mg/m 2 ) was given fortnightly up to a maximum of four doses. Immunologic subset monitoring was performed at baseline and regular intervals until relapse. Median follow-up duration postrituximab was 26.7 months (range =6.5-66.5 months). Baseline immunologic subsets were examined for association with rituximab response defined as resolution of proteinuria with discontinuation of prednisolone and CNI 3 months postrituximab.Results Twelve patients (54.5%) responded to rituximab. Mitogen-stimulated CD154 + CD4 + CD3 + subset before rituximab was significantly lower in FSGS responders compared with nonresponders (54.9%628.1% versus 78.9%616.4%; P=0.03). IFN-g + CD3 + and IL-2 + CD3 + were similarly decreased in responders compared with nonresponders (0.6%60.8% versus 7.5%66.1%; P=0.003 and 0.2%60.5% versus 4.0%64.7%; P,0.01, respectively). Recovery of all three activation subsets occurred 6 months postrituximab treatment (CD154 + CD4 + CD3 + , 74.8%617.2%; IFN-g + CD3 + , 7.1%67.7%; and IL-2 + CD3 + , 7.9%610.9%; P,0.01). Receiver-operating characteristic analysis using optimal cutoff values showed that activated CD154 + CD4 + CD3 + ,83.3% (area under the curve [AUC], 0.81; 95% confidence interval [95% CI], 0.61 to 1.00), IFN-g + CD3 + ,2.5% (AUC, 0.90; 95% CI, 0.75 to 1.00), and IL-2 + CD3 + ,0.3% (AUC, 0.78; 95% CI, 0.57 to 0.98) were good predictors of rituximab response.Conclusions We have identified prognostic markers that define a subset of patients with FSGS bearing an immunologic signature representing hyporesponsiveness to T cell stimulation and therefore, who respond better to rituximab.

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Efficacy and safety of rituximab treatment in children with primary glomerulonephritis

Abstract: In conclusion, we postulate that alternative rituximab therapy should be taken into consideration in nephrotic patients not responding to standard therapy.

Cited by 10 publications

References 0 publications

Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy

Rituximab Exhibits Altered Pharmacokinetics in Patients With Membranous Nephropathy

Multicenter analysis of the efficacy and safety of a non‐standard immunosuppressive therapy with rituximab in children with steroid‐resistant nephrotic syndrome

T Lymphocyte Activation Markers as Predictors of Responsiveness to Rituximab among Patients with FSGS

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