Late-onset adverse events after a single dose of rituximab in children with complicated steroid-dependent nephrotic syndrome

Fujinaga, Shuichiro; Ozawa, K.; Sakuraya, Koji; Yamada, Akifumi; Shimizu, Toshiaki

doi:10.5414/cn108835

Cited by 26 publications

(14 citation statements)

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“…43,74,85 A condition that has become more frequent in recent years is hypogammaglobulinemia associated with the use of rituximab, an anti-CD20 monoclonal antibody indicated for some autoimmune diseases, lymphoproliferative syndromes, or refractory nephrotic syndrome. This type of hypogammaglobulinemia affects up to 50% of patients, especially those on regular use of rituximab; is symptomatic in less than 10% of cases, and can persist for a long time 86-89 requiring Ig replacement, either intravenous or subcutaneous. 90 Persistent hypogammaglobulinemia may occur in a small group of genetically predisposed patients on rituximab.…”

Section: Indications and Efficacy Of Human Immunoglobulin In Primary mentioning

confidence: 99%

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

Goudouris

Silva

Ouricuri

et al. 2017

Einstein (São Paulo)

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In the last few years, new primary immunodeficiencies and genetic defects have been described. Recently, immunoglobulin products with improved compositions and for subcutaneous use have become available in Brazil. In order to guide physicians on the use of human immunoglobulin to treat primary immunodeficiencies, based on a narrative literature review and their professional experience, the members of the Primary Immunodeficiency Group of the Brazilian Society of Allergy and Immunology prepared an updated document of the 1st Brazilian Consensus, published in 2010. The document presents new knowledge about the indications and efficacy of immunoglobulin therapy in primary immunodeficiencies, relevant production-related aspects, mode of use (routes of administration, pharmacokinetics, doses and intervals), adverse events (major, prevention, treatment and reporting), patient monitoring, presentations available and how to have access to this therapeutic resource in Brazil.

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Section: Indications and Efficacy Of Human Immunoglobulin In Primary mentioning

confidence: 99%

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

Goudouris

Silva

Ouricuri

et al. 2017

Einstein (São Paulo)

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“…Regarding the risk of severe infections following RTX infusion in paediatric patients affected by NS, among the 27 patients showing post-RTX IgG hypogammaglobulinemia (including our patients and other in the literature with available follow-up)[5,6], no life-threatening infections were detected. Among non-life-threatening infections, one patient presented bronchitis[6], one enteritis[6], and one recurrent episodes of acute otitis media. Moreover, evaluating the need of substitutive IgG infusion, 4 out of the 27 patients underwent IgG supplementation.…”

Section: Discussionmentioning

confidence: 86%

“…Delbe-Bertin et al[5] reported that persisting post-RTX IgG hypo-gammaglobulinemia was observed in 7 patients with IgG hypogammaglobulinemia before RTX infusion, while none of the 4 patients with normal pre-RTX IgG levels presented IgG hypogammaglobulinemia after RTX initiation. In addition, Fujinaga et al[6] found that nine out of 60 patients with complicated steroid-dependent NS showed hypogammaglobulinemia (defined as IgG levels < 500 mg/dL) after RTX infusion. Among these 9 patients, only 3 patients had normal IgG levels before the RTX infusion.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, evaluating the need of substitutive IgG infusion, 4 out of the 27 patients underwent IgG supplementation. Among these 4 patients, 3 received IgG supplementation only for low IgG levels[5,6], and one for recurrent acute otitis media. It is important to emphasize that one of these patients in IgG supplementation presented aseptic meningitis as an adverse effect of IgG supplementation[5].…”

Section: Discussionmentioning

confidence: 99%

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Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values

Marzuillo

Guarino

Esposito

et al. 2019

WJCC

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BACKGROUND In paediatric patients with complicated nephrotic syndrome (NS), rituximab (RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal immunoglobulin G (IgG) levels. AIM To evaluate the effect of RTX on IgG levels and infections in patients with complicated NS and normal basal IgG levels. METHODS We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to the IgG normal values for age [mean ± standard deviation (SD)]. RESULTS We enrolled 20 patients with mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients (55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two “starting doses” experienced normalization of IgG levels. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third dose, 44.1% after the fourth dose, and 35.5% after the fifth dose. CONCLUSION RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values. None of the treated patients showed severe infections.

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“…Although rituximab is generally safe and well tolerated in most children, there are potentially serious adverse events that require caution: hypogammaglobulinemia, late-onset neutropenia, hepatitis B reactivation, serious infusion-related adverse events and infections, the latter with potentially fatal outcome with reports of Pneumocystis jirovecii pneumonia and progressive multifocal leukoencephalopathy [8, 58,59,61,62,117,118] hematologic adverse effects are reported more often and more severely in younger children. In previous studies with SRNS [41] as well as with SDNS [119], those patients who developed severe neutropenia and hypogammaglobulinemia were aged under 10 years. In addition, in a Japanese multicentre study involving 114 children, the median age was significantly younger in patients with more severe hematologic adverse effects (6.4 vs. 11.5 years) [120].…”

Section: Anti-cd20 Monoclonal Antibodiesmentioning

confidence: 99%

Current understandings in treating children with steroid-resistant nephrotic syndrome

et al. 2020

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Steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatric nephrologists. SRNS is viewed as a heterogeneous disease entity including immune-based and monogenic aetiologies. Because SRNS is rare, treatment strategies are individualized and vary among centres of expertise. Calcineurin inhibitors (CNI) have been effectively used to induce remission in patients with immune-based SRNS; however, there is still no consensus on treating children who become either CNI-dependent or CNI-resistant. Rituximab is a steroid-sparing agent for patients with steroid-sensitive nephrotic syndrome, but its efficacy in SRNS is controversial. Recently, several novel monoclonal antibodies are emerging as treatment option, but their efficacy remains to be seen. Non-immune therapies, such as angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, have been proven efficacious in children with SRNS and are recommended as adjuvant agents. This review summarizes and discusses our current understandings in treating children with idiopathic SRNS.

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Late-onset adverse events after a single dose of rituximab in children with complicated steroid-dependent nephrotic syndrome

Abstract: Although neutropenia and hypogammaglobulinemia should be kept in mind as late-onset adverse events of RTX therapy in patients with complicated SDNS, severe infections during B-cell depletion periods are infrequent when our treatment strategies are implemented.

Cited by 26 publications

References 0 publications

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

II Brazilian Consensus on the use of human immunoglobulin in patients with primary immunodeficiencies

Rituximab-induced IgG hypogammaglobulinemia in children with nephrotic syndrome and normal pre-treatment IgG values

Current understandings in treating children with steroid-resistant nephrotic syndrome

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