Rituximab-associated hypogammaglobulinemia in children with idiopathic nephrotic syndrome: results of an ESPN survey

Abstract

Background There is paucity of information on rituximab-associated hypogammaglobulinemia (HGG) and its potential infectious consequences in children treated for idiopathic nephrotic syndrome (INS). Methods A survey was distributed by the European Society Pediatric Nephrology to its members. It addressed the screening and management practices of pediatric nephrology units for recognizing and treating RTX-associated HGG and its morbidity and mortality. Eighty-four centers which had treated an overall 1328 INS children with RTX responded. Results The majority of centers administered several courses of RTX and continued concomitant immunosuppressive therapy. Sixty-five percent of centers routinely screened children for HGG prior to RTX infusion, 59% during, and 52% following RTX treatment. Forty-seven percent had observed HGG prior to RTX administration, 61% during and 47% >9 months following treatment in 121, 210, and 128 subjects respectively. Thirty-three severe infections were reported among the cohort of 1328 RTX-treated subjects, of whom 3 children died. HGG had been recognized in 30/33 (80%) of them. Conclusions HGG in steroid-dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS) children is probably multifactorial and can be observed prior to RTX administration in children with SDNS/FRNS. Persistent HGG lasting >9 months from RTX infusion is not uncommon and may increase the risk of severe infections in this cohort. We advocate for the obligatory screening for HGG in children with SDNS/FRNS prior to, during, and following RTX treatment. Further research is necessary to identify risk factors for developing both HGG and severe infections before recommendations are made for its optimal management. Graphical abstract

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

“…Furthermore, there were no cases of RTX discontinuation due to these adverse events. While hypogammaglobulinemia events were less frequent in our study, previous studies have shown that hypogammaglobulinemia is a common complication of RTX treatment in children with SDNS [10,14,33]. This event might have been underestimated in our study because we did not routinely check immunoglobulin levels.…”

“…In a European survey, 65% and 59% of centers reported regularly monitoring immunoglobulin G levels before and after RTX administration [33]. While a retrospective study showed no signi cant association between hypogammaglobulinemia severity and infection [15], another study reported that 80% of patients with severe infections had hypogammaglobulinemia [33]. Clinicians need to monitor impaired immune function following RTX treatment, particularly in younger patients at higher risk for hypogammaglobulinemia, as reported in previous studies [10,34].…”

“…This event might have been underestimated in our study because we did not routinely check immunoglobulin levels. In a European survey, 65% and 59% of centers reported regularly monitoring immunoglobulin G levels before and after RTX administration [33]. While a retrospective study showed no signi cant association between hypogammaglobulinemia severity and infection [15], another study reported that 80% of patients with severe infections had hypogammaglobulinemia [33].…”

Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment

“…Authors reported that hypogammaglobulinemia was observed in around 35% of treated subjects. However that hypogammaglobulinemia may persist several months after the last rituximab infusion is commonly reported, but if the hypogammaglobulinemia would be related to a major risk of severe infections is still to be completely defined ( 58 ).…”

Rituximab in idiopathic nephrotic syndrome: still waiting for stronger evidences

“…However, unlike other immunosuppressive therapies, there is a lack of long-term follow-up data on RTX use in INS. To address this gap, the European Society of Pediatric Nephrology (ESPN) conducted a survey in 84 centers, involving 1328 children, to gather information on RTX-associated hypogammaglobulinemia and its potential consequences in INS 9 . This survey provides valuable insights as it reflects the common practice of pediatric nephrologists outside of research protocols and includes a robust number of patients.…”