Prophylactic rituximab administration in children with complicated nephrotic syndrome

Okutsu, Mika; Kamei, Koichi; Mai, Sabine; Kanamori, Toru; Nishi, Kentaro; Ishiwa, Sho; Ogura, Masao; Sako, Mayumi; Ito, Shuichi; Ishikura, Kenji

doi:10.1007/s00467-020-04771-5

Cited by 5 publications

(6 citation statements)

References 29 publications

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“…Cholesterol levels may re ect the degree of control of NS since patients with NS have elevated cholesterol levels immediately after remission of proteinuria. Similar to our ndings, the duration of B-cell depletion after RTX injection was between 5.1 and 6.1 months in the previous studies evaluating repeated RTX treatment [10,11,25]. Chan et al showed that the B-cell depletion period remained consistent after redosing in children with SDNS who received two or more courses of RTX [10].…”

Section: Discussionsupporting

confidence: 90%

Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome

Choi

Min

Kim

et al. 2023

Preprint

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Background We aimed to investigate the efficacy and safety of long-term repeated use of Rituximab (RTX) in pediatric patients with nephrotic syndrome (NS). Methods Retrospective review of medical records for 50 patients with steroid-dependent NS (SDNS) who had received more than three cycles of RTX was conducted; each consisted of one to four infusions of RTX until B lymphocytes were depleted. Results The median age of starting the first RTX cycle was 12.4 years (interquartile ranges (IQR) 10.2–14.6). During a median follow-up period of 6.3 (IQR 3.6–8.6) years, patients received a median of 5.0 RTX cycles (IQR 4.0–7.3). The number of relapses decreased from a median of 2.0 relapses per year (IQR 1.0–3.0) to 0.2 relapses per year (IQR 0.0–0.5) after long-term RTX treatments (P < 0.001). Longer relapse-free periods were associated with more than four RTX cycles, longer B cell depletion, older age at each RTX treatment, and lower cholesterol levels. B lymphocytes recovered to 1% at a median of 5.9 months (95% confidence interval (CI) 5.7–6.1) after RTX administration. Factors related to a longer period of B-cell depletion included more than five RTX cycles, a higher dose of RTX, older age at treatment, and concurrent use of antimetabolites. During repeated RTX treatments, 11%, 6%, and 2% of patients developed hypogammaglobulinemia, severe infection, and severe neutropenia, respectively. Conclusions Long-term repeated use of RTX was effective and safe in pediatric NS patients. Furthermore, the redosing of RTX could be chosen by considering predictive factors for relapse-free and B-cell depletion periods.

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Section: Discussionsupporting

confidence: 90%

Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome

Choi

Min

Kim

et al. 2023

Preprint

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show abstract

“…Similar to our ndings, the duration of B-cell depletion after RTX injection was between 5.1 and 6.1 months in the previous studies evaluating repeated RTX treatment [10,11,25]. Chan et al showed that the B-cell depletion period remained consistent after redosing in children with SDNS who received two or more courses of RTX [10].…”

Section: Discussionsupporting

confidence: 90%

“…This study found that a more extended relapse-free period was associated with a longer duration of B-cell depletion, older age at each RTX treatment, female sex, and lower cholesterol levels. RTX has previously been shown to maintain remission in NS patients during B-cell depletion effectively [11,[19][20][21]. However, this study is the rst to identify the B-cell depletion period as a predictive factor for the relapse-free period.…”

Section: Discussionmentioning

confidence: 82%

“…Due to its relative effectiveness compared to other steroid-sparing agents, RTX is widely used in clinical practice, and the number of patients receiving repeated administration is increasing. Previous studies have shown that repeated RTX treatment improves clinical outcomes, and adverse events such as hypogammaglobulinemia, agranulocytosis, and infections were tolerable in children with SDNS [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 98%

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Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome

Choi,

Min,

Kim

et al. 2023

Pediatr Nephrol

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BackgroundWe aimed to investigate the e cacy and safety of long-term repeated use of Rituximab (RTX) in pediatric patients with nephrotic syndrome (NS). MethodsRetrospective review of medical records for 50 patients with steroid-dependent NS (SDNS) who had received more than three cycles of RTX was conducted; each consisted of one to four infusions of RTX until B lymphocytes were depleted. ResultsThe median age of starting the rst RTX cycle was 12.4 years (interquartile ranges (IQR) 10.2-14.6).During a median follow-up period of 6.3 (IQR 3.6-8.6) years, patients received a median of 5.0 RTX cycles (IQR 4.0-7.3). The number of relapses decreased from a median of 2.0 relapses per year (IQR 1.0-3.0) to 0.2 relapses per year (IQR 0.0-0.5) after long-term RTX treatments (P < 0.001). Longer relapse-free periods were associated with more than four RTX cycles, longer B cell depletion, older age at each RTX treatment, and lower cholesterol levels. B lymphocytes recovered to 1% at a median of 5.9 months (95% con dence interval (CI) 5.7-6.1) after RTX administration. Factors related to a longer period of B-cell depletion included more than ve RTX cycles, a higher dose of RTX, older age at treatment, and concurrent use of antimetabolites. During repeated RTX treatments, 11%, 6%, and 2% of patients developed hypogammaglobulinemia, severe infection, and severe neutropenia, respectively. ConclusionsLong-term repeated use of RTX was effective and safe in pediatric NS patients. Furthermore, the redosing of RTX could be chosen by considering predictive factors for relapse-free and B-cell depletion periods.

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“…In a retrospective study of 61 children with frequently relapsing, steroid-dependent nephrotic syndrome, patients receiving prophylactic rituximab at B-cell recovery (CD19 >1%) had a significantly longer relapse-free period after last rituximab (667 versus 335 days) compared with the nonprophylaxis group. 113 Results from the ongoing RITURNS II study on steroid-dependent nephrotic syndrome evaluating the effect of adding maintenance MMF from 4 months post-rituximab versus prophylactic rituximab therapies at 8 and 18 months (ClinicalTrials.gov identifier: NCT03899103) 114 will provide evidence to guide subsequent treatments.…”

Section: Redosing Approachesmentioning

confidence: 99%

Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome

Chan

Yap

Colucci

et al. 2022

CJASN

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Rituximab is an established therapy in children with idiopathic nephrotic syndrome to sustain short to medium term disease remission and avoid steroid toxicities. Recent trials focus on its use as a first-line agent among those with milder disease severity. Rituximab is used in multi-drug refractory nephrotic syndrome and post-transplant disease recurrence, although the evidence is much less substantial. Available data suggest that the treatment response to rituximab depends on various patient factors, dosing regimen and the concomitant use of maintenance immunosuppression. Following repeated treatments, patients are found to have an improving response overall with longer relapse-free period. The drug effect, however, is not permanent and 80% of patients eventually relapse and many will require an additional course of rituximab. This underpins the importance to understand the long-term safety profile upon repeated treatments. Although rituximab appears to be generally safe, there are concerns of long-term hypogammaglobulinaemia, especially in young children. Reliable immunophenotyping and biomarkers are yet to be discovered to predict treatment success, risk of both rare and severe side-effects, persistent hypogammaglobulinaemia and to guide on re-dosing strategy. In this review, we highlight recent advances on the use of rituximab for childhood nephrotic syndrome and how the therapeutic landscape is evolving.

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Prophylactic rituximab administration in children with complicated nephrotic syndrome

Cited by 5 publications

References 29 publications

Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome

Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome

Efficacy and safety of long-term repeated use of rituximab in pediatric patients with nephrotic syndrome

Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome

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