Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome

Br J Clin Pharmacol. 2018 Jun;84(6):1238-1249. doi: 10.1111/bcp.13548. Epub 2018 Mar 25.

Abstract

Aims: Anti-CD20 antibodies are increasingly being used to treat idiopathic nephrotic syndrome (INS) in children. While they may allow steroid and calcineurin inhibitor withdrawal, repeated infusions of anti-CD20 antibodies are often required to maintain remission. Data on their potential toxicity in INS are needed, to consider repeated infusions.

Methods: We investigated the side effects associated with the use of rituximab (a chimeric antibody; 130 patients) and ofatumumab (a humanized antibody; 37 patients) in children with INS (steroid-dependent and steroid/calcineurin inhibitor-dependent disease) treated at a national referral centre over a 9-year period (400 treatments; follow-up 1-9 years).

Results: Infusion reactions were mainly absent in children with steroid-dependent disease. Rash, dyspnoea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion, respectively) were resolved by using premedication with salbutamol. Other short-term reactions (up to 3 months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3-9 months following infusion, were similarly common in the two groups and resolved with targeted therapies [antibiotic, fluconazole, immunoglobulins (Igs), etc.]. The number of circulating CD19/20 cells fell to 0 at month 1 and were reconstituted at month 3; circulating IgG antibodies remained within the normal range for 1 year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein-Barr virus and John Cunningham virus activation markers were occasionally observed.

Conclusion: Overall, the toxicity of anti-CD20 monoclonal antibodies was limited to post-infusion side effects in children with more complex disease. The relatively safe profile of anti-CD20 antibodies supports their use as steroid-sparing agents in children with INS.

Keywords: nephrotic syndrome; ofatumumab; rituximab; side effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20 / immunology*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / adverse effects*
  • Infusions, Intravenous
  • Male
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / immunology
  • Patient Safety
  • Risk Assessment
  • Risk Factors
  • Rituximab / administration & dosage
  • Rituximab / adverse effects*
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • Immunologic Factors
  • Rituximab
  • ofatumumab

Supplementary concepts

  • Nephrosis, congenital