Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes: Kidney International

E.Y.-H. Chan, H. Webb, E. Yu, G.M. Ghiggeri, M.J. Kemper, A.L.-T. Ma, T. Yamamura, A. Sinha, A. Bagga, J. Hogan, C. Dossier, M. Vivarelli, I.D. Liu, K. Kamei, K. Ishikura, P. Saini, K. Tullus

Research output: Contribution to journalArticlepeer-review

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. © 2019 International Society of Nephrology
Original languageEnglish
Pages (from-to)393-401
Number of pages9
JournalKidney Int.
Volume97
Issue number2
DOIs
Publication statusPublished - 2020

Keywords

  • biologics
  • children
  • immunosuppression
  • nephrotic syndrome
  • rituximab
  • steroid-dependent nephrotic syndrome
  • calcineurin
  • corticosteroid
  • mycophenolic acid
  • adolescent
  • Article
  • Asia
  • child
  • cohort analysis
  • controlled study
  • death
  • disease classification
  • drug megadose
  • drug safety
  • Europe
  • female
  • follow up
  • geographic distribution
  • hazard ratio
  • human
  • human tissue
  • immunoglobulin deficiency
  • immunosuppressive treatment
  • infection
  • infusion related reaction
  • injection site reaction
  • kidney biopsy
  • low drug dose
  • maintenance therapy
  • major clinical study
  • male
  • multicenter study
  • multiple cycle treatment
  • neutropenia
  • North America
  • priority journal
  • recurrence free survival
  • retrospective study
  • steroid dependent frequently relapsing nephrotic syndrome
  • survival
  • treatment outcome

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