Hypogammaglobulinaemia following rituximab therapy in childhood nephrotic syndrome

Chan, Eugene Yu-hin; Lap-tak, Alison; Tullus, Kjell

doi:10.1007/s00467-021-05345-9

Cited by 11 publications

(14 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Preexisting hypogammaglobulinemia is common among children with NS due to urinary loss and immunosuppression use, and tends to persist after rituximab therapy. 34 Because .80% of rituximab redoses were due to relapse, the high prevalence of hypogammaglobulinemia reported might partly be due to the aforementioned factors rather than rituximab alone. The development of hypogammaglobulinemia was not related to cumulative dose, 18 rituximab regimen, nor maintenance immunosuppression.…”

Section: Discussionmentioning

confidence: 99%

“…This observation echoes our findings that duration of immunosuppression use contributes to the protective effect on disease relapse. However, immunosuppression use should be balanced against potential adverse events, such as infection, especially in the presence of additional risk factors, such as hypogammaglobulinemia and neutropenia 34 . Of note, histology has not been identified as a predictive factor of relapse 6 , 31 , 32 .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Chan

Yu²,

Angeletti

et al. 2022

JASN

Self Cite

View full text Add to dashboard Cite

Background: Long-term outcomes following multiple rituximab courses among children with frequently-relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown. Methods: A retrospective cohort study at 16 pediatric nephrology centers from 10 countries in Asia, Europe, and North America included children with FRSDNS who received ≥2 rituximab courses. Primary outcomes were relapse-free survival and adverse events. Results: 346 children (age 9.8 years, IQR 6.6-13.5; 73% boys) received 1149 rituximab courses. 145, 83, 50, 28, 22, and 18 children received 2, 3, 4, 5, 6 and ≥7 courses, respectively. Median follow-up was 5.9 years (IQR, 4.3-7.7). Relapse-free survival differed by treatment courses (clustered log-rank test p<0.001). Compared to the first course (10.0 months, 95% CI, 9.0-10.7), relapse-free period and relapse risk progressively improved following subsequent courses (12.0-16.0 months; HRadj, 0.03-0.13; 95% CI, 0.01-0.18; ps<0.001). B-cell depletion duration remained similar with repeated treatments (6.1 months, 95% CI, 6.0-6.3). Adverse events were mostly mild, most commonly hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 vs 3.3 years; p=0.05) and at first rituximab (8.0 y vs 10.0 years; p=0.01) and history of steroid resistance (28% vs 18%; p=0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% vs 20%, p=0.04). Upon last follow-up, 332 children (96%) had normal kidney function. Conclusion: Children receiving repeated rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable but significant complications can occur. These findings support repeated rituximab use in FRSDNS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Chan

Yu²,

Angeletti

et al. 2022

JASN

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hypogammaglobulinemia is common and ranges from 14% to 58% after rituximab in children treated for nephrotic syndrome. 6,33,60,76,[81][82][83] Up to 40% of the treated children experience persistent hypogammaglobulinemia even 2 years after the last rituximab infusion. 82 The true incidence and significance of rituximab-induced hypogammaglobulinemia, however, was poorly investigated due to the lack of prospective study that provides consistent immunoglobulin monitoring and a comparative control group of children with nephrotic syndrome who only receive oral immunosuppression.…”

Section: Hypogammaglobulinemiamentioning

confidence: 99%

“…Other factors contributing to infectious complications include underlying disease (e.g., lupus), concurrent immunosuppression, and coexisting complications such as neutropenia. 76,82,83,[95][96][97][98] The indications when intravenous immunoglobulin substitution is required are not well defined, and current guidelines do not recommend replacement at a definitive cutoff. 61,99…”

Section: Lower Risk Of Relapsementioning

confidence: 99%

“…9 The benefit of immunoglobulin substitution to prevent infection is unclear and should be individualized according to the aforementioned risk factors for infection. 76 Recent advances have provided important new knowledge on the use of rituximab in nephrotic syndrome, yet many outstanding clinical and research questions remain (Table 6). Although all children receiving rituximab are classified as having frequently relapsing, steroid-dependent nephrotic syndrome, their clinical courses are heterogeneous.…”

Section: Treatment Recommendationsmentioning

confidence: 99%

See 1 more Smart Citation

Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome

Chan

Yap

Colucci

et al. 2022

CJASN

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Therapeutic drug monitoring in childhood idiopathic nephrotic syndrome: a state of the art review

et al. 2023

View full text Add to dashboard Cite

Hypogammaglobulinaemia following rituximab therapy in childhood nephrotic syndrome

Cited by 11 publications

References 30 publications

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study

Use of Rituximab in Childhood Idiopathic Nephrotic Syndrome

Therapeutic drug monitoring in childhood idiopathic nephrotic syndrome: a state of the art review

Contact Info

Product

Resources

About