Predictors of relapse and long-term outcome in children with steroid-dependent nephrotic syndrome after rituximab treatment

Fujinaga, Shuichiro; Hirano, Daishi; Mizutani, Akira; Sakuraya, Koji; Yamada, Akifumi; Sakurai, Shunsuke; Shimizu, Toshiaki

doi:10.1007/s10157-016-1328-y

Cited by 24 publications

(20 citation statements)

References 25 publications

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“…Another concern regarding rituximab use in children with NS is the lack of long term safety data. The use of multiple courses over multiple years in the same child have been reported by studies at the time of relapses and/ or the time of CD count recovery with no reported significant side effects (31, 36, 42, 52, 57, 100, 131). However, it is not yet known how many doses can be considered safe in children with NS.…”

Section: Side Effects Of Rituximabmentioning

confidence: 85%

“…Children with SDNS or FRNS, and especially those with SRNS whose disease is difficult to control, are often continued on various doses of other immunosuppressive agents such as MMF or CNIs to try to maintain them in remission and decrease the rate of relapses (97–100). In this context, there is currently a multicenter randomized trial underway to test the benefit of using MMF following rituximab therapy in children with FRNS or SDNS (101).…”

Section: Factors That May Affect the Clinical Response Of Rituximab Imentioning

confidence: 99%

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Rituximab Use in the Management of Childhood Nephrotic Syndrome

2019

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Childhood nephrotic syndrome is a challenging and often persistent renal disorder, and its incidence varies between different ethnicities and regions. Corticosteroids have been the main treatment for decades and are effective in most children with idiopathic NS, although 10–15% of these children become steroid resistant. Furthermore, some initially steroid sensitive children follow a steroid dependent or frequently relapsing course and are therefore at increased risk for developing steroid toxicity. In such children, alternative immunosuppressive medications are used to induce and/or maintain remission of NS. One such drug, rituximab, is a monoclonal antibody directed against the B lymphocyte CD20 marker which induces depletion of B cells, and has shown promising results in the management of NS in children. In this review, we summarize recent studies on the efficacy and safety of rituximab in the different types of childhood nephrotic syndrome, the known and potential mechanisms of action of rituximab, its possible complications and side effects, and the available and potential biomarkers of rituximab activity.

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Section: Side Effects Of Rituximabmentioning

confidence: 85%

Section: Factors That May Affect the Clinical Response Of Rituximab Imentioning

confidence: 99%

Rituximab Use in the Management of Childhood Nephrotic Syndrome

2019

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“…Fujinaga et al (16) studied the predictors of relapse and long-term outcome in 43 SDNS patients given a single dose of RTX as induction treatment. In all, 91% of their patients relapsed.…”

Section: Discussionmentioning

confidence: 99%

Rituximab for Children With Difficult-to-Treat Nephrotic Syndrome: Its Effects on Disease Progression and Growth

et al. 2019

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Background: Since the early 2000s rituximab (RTX) has been thought of as an alternative treatment for steroid-sensitive nephrotic syndrome (SSNS) and steroid-resistant nephrotic syndrome (SRNS). Objective: This study aimed to determine the effects of RTX treatment on disease outcome and growth in pediatric SSNS and SRNS patients. Materials and Methods: The medical records of pediatric SSNS and SRNS patients that began RTX treatment at the mean age of 10.8 ± 5.1 years between 2009 and 2017 were retrospectively reviewed. Additionally, the effect of RTX on growth was evaluated based on patient height, weight, and BMI z scores. Results: The study included 41 children, of which 21 had SSNS and 20 had SRNS. Mean age at diagnosis of NS was 5.8 ± 4.7 years. Mean duration of post-RTX treatment follow-up was 2.3 ± 1.6 years. Among the SSNS patients, 6 and 11 patients were steroid free and calcineurin inhibitor free at the last follow-up visit, respectively. The 1-year cumulative steroid and calcineurin inhibitor doses both decreased after RTX treatment, as compared to before RTX ( P = 0.001 and P = 0.015, respectively). The median height z -score at the time of RTX initiation was −1.2 and the median height z -score at the last follow-up visit was −0.6 ( P = 0.044). The median BMI z -score decreased from 1.6 (IQR; 0.9–3.0) at the time RTX was initiated to 1.1 IQR; [(−0.7)−2.5] at the last follow-up visit ( P = 0.007). At the last follow-up visit 4 SRNS patients had complete remission and 4 had partial remission. The 1-year cumulative steroid dosage in the SRNS patients decreased significantly after RTX, as compared to before RTX ( P = 0.001). The median height z -score at the time of RTX initiation was −0.8 and the median height z -score at the last follow-up visit was −0.7 ( P = 0.81). The median BMI z -score decreased from 0.3 at the time RTX was initiated to −0.1 at the last follow-up visit ( P = 0.11). Conclusion: RTX has a more positive effect on disease outcome and growth in SSNS patients than in those with SRNS.

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“…Fujinaga reported 24-month relapse rates on a low-dose regimen, reporting 91% relapse (39 patients) at a median of 586 days [28]. Greater risk of relapse was associated with younger age of administration and more rapid reconstitution of B cells [28].…”

Section: Discussionmentioning

confidence: 99%

“…Greater risk of relapse was associated with younger age of administration and more rapid reconstitution of B cells [28]. …”

Section: Discussionmentioning

confidence: 99%

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

Maxted¹,

Dalrymple

Chisholm

et al. 2018

Pediatr Nephrol

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ObjectiveRituximab is an effective treatment for children with steroid dependent or frequently relapsing nephrotic syndrome. The optimum dosing schedule for rituximab has not been established. We hypothesized that a single low dose of 375 mg/m2 would have comparable outcomes to higher doses in reducing the frequency of relapse and time to B cell reconstitution.MethodsWe conducted a multicenter retrospective observational cohort study of children with steroid-sensitive frequently relapsing nephrotic syndrome. Data were extracted from clinical records including the dates of diagnosis, treatment, relapses, the use of concomitant immunosuppression, and lymphocyte subset profiling. Patients treated earlier received variable doses of rituximab, although typically two doses of 750 mg/m2. Later, patients received the current regimen of a single dose of 375 mg/m2. The primary outcome was an absence of clinically confirmed relapse 12 months following rituximab administration. Secondary outcomes were median time to relapse, probability of being relapse-free at 6 and 24 months and time to reconstitution of CD19+ B cells.ResultsSixty patients received 143 courses of rituximab. Seven different dosing regimen strategies were used, ranging between 375 and 750 mg/m2 per dose, with administration of 1–4 doses. There was no significant difference in event-free survival at 12 months between dosing strategies. The median time to reconstitution of B cells was not significantly different between groups.ConclusionsUse of a single low-dose regimen of rituximab in the management of frequently relapsing nephrotic syndrome does not affect the probability of relapse at 12 months or time to B cell reconstitution compared to a conventional higher dose.Electronic supplementary materialThe online version of this article (10.1007/s00467-018-4172-3) contains supplementary material, which is available to authorized users.

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Predictors of relapse and long-term outcome in children with steroid-dependent nephrotic syndrome after rituximab treatment

Abstract: The introduction of RTX may not be necessarily associated with improved long-term outcome.

Cited by 24 publications

References 25 publications

Rituximab Use in the Management of Childhood Nephrotic Syndrome

Rituximab Use in the Management of Childhood Nephrotic Syndrome

Rituximab for Children With Difficult-to-Treat Nephrotic Syndrome: Its Effects on Disease Progression and Growth

Low-dose rituximab is no less effective for nephrotic syndrome measured by 12-month outcome

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