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Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic
Eugene Yu-Hin Chan1, Hazel Webb2, Ellen Yu3
1Department of Paediatric Nephrology, Great Ormond Street Hospital for Children National Health Service Trust, London, UK; Paediatric Nephrology Centre, Department of Paediatrics, Princess Margaret Hospital, Hong Kong; Paediatric Nephrology Centre, Department of Paediatrics, Hong Kong Children's Hospital, Hong Kong.
Insights
Optimal rituximab dosing for pediatric nephrotic syndrome is key. Low-dose rituximab without maintenance immunosuppression led to shorter relapse-free survival in children with steroid-dependent/frequently-relapsing nephrotic syndrome (SDFRNS).
Area of Science:
- Pediatric Nephrology
- Immunology
- Pharmacology
Background:
- Rituximab is a recognized treatment for steroid-dependent/frequently-relapsing nephrotic syndrome (SDFRNS) in children.
- The optimal rituximab regimen, including dosage and concurrent immunosuppression, for pediatric SDFRNS remains undetermined.
Purpose of the Study:
- To investigate the impact of different rituximab dosing levels (low, medium, high) and the presence or absence of maintenance immunosuppression on treatment outcomes in pediatric SDFRNS.
- To identify the most effective rituximab regimen for improving relapse-free survival in children with complicated SDFRNS.
Main Methods:
- International, multicenter retrospective study involving 511 children (1-18 years) with complicated SDFRNS treated between 2005-2016.
- Analysis of rituximab doses: low (375mg/m²), medium (750mg/m²), and high (1125-1500mg/m²).
- Evaluation of maintenance immunosuppression (corticosteroids, mycophenolate mofetil, calcineurin inhibitors) and its effect on relapse-free survival.
Main Results:
- Without maintenance immunosuppression, low-dose rituximab was associated with significantly shorter relapse-free survival (8.5 months) compared to medium (12.7 months) and high doses (14.3 months).
- With maintenance immunosuppression, relapse-free survival differences between low, medium, and high rituximab doses were not statistically significant.
- Minimal change disease was the predominant histology (74%) in the 317 children who underwent renal biopsy; most adverse events were mild.
Conclusions:
- Low-dose rituximab without maintenance immunosuppression is linked to the shortest relapse-free survival in pediatric patients with SDFRNS.
- Both rituximab dosage and the use of maintenance immunosuppression are critical factors influencing treatment outcomes in pediatric nephrotic syndrome.
Abstract:
Rituximab is an effective treatment for steroid-dependent/ frequently-relapsing nephrotic syndrome (SDFRNS) in children. However, the optimal rituximab regimen remains unknown. To help determine this we conducted an international, multicenter retrospective study at 11 tertiary pediatric nephrology centers in Asia, Europe and North America of children 1-18 years of age with complicated SDFRNS receiving rituximab between 2005-2016 for 18 or more months follow-up. The effect of rituximab prescribed at three dosing levels: low (375mg/m2), medium (750mg/m2) and high (1125-1500mg/m2), with or without maintenance immunosuppression (defined as concurrent use of corticosteroids, mycophenolate motile or calcineurin inhibition at first relapse or for at least six months following the rituximab treatment) was examined. Among the 511 children (median age 11.5 year, 67% boys), 191, 208 and 112 received low, medium and high dose rituximab, respectively. Within this total cohort of 511 children, 283 (55%) received maintenance immunosuppression. Renal biopsies were performed in 317 children indicating the predominant histology was minimal change disease (74%). Without maintenance immunosuppression, low-dose rituximab had a shorter relapse-free period and a higher relapse risk (8.5 months) than medium (12.7 months; adjusted hazard ratio, 0.62) and high dose (14.3 months; adjusted hazard ratio, 0.50; all significant). With maintenance immunosuppression, the relapse-free survival in low-dose rituximab (14 months) was similar to medium (10.9 months; adjusted hazard ratio, 1.23) and high dose (12.0 months; adjusted hazard ratio, 0.92; all non-significant). Most adverse events were mild. Thus, children receiving low-dose rituximab without maintenance immunosuppression had the shortest relapse-free survival. Hence, both rituximab dose and maintenance immunosuppression have important effects on the treatment outcomes.
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