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

Alice Bonanni, Marta Calatroni, Matteo D'Alessandro, Sara Signa, Enrica Bertelli, Michela Cioni, Eddi Di Marco, Roberto Biassoni, Gianluca Caridi, Giulia Ingrasciotta, Roberta Bertelli, Armando Di Donato, Maurizio Bruschi, Alberto Canepa, Giorgio Piaggio, Pietro Ravani, Gian Marco Ghiggeri

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1238-1249
Number of pages12
JournalBritish Journal of Clinical Pharmacology
Volume84
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

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Antibodies, Monoclonal, Humanized
Anti-Idiotypic Antibodies
Steroids
JC Virus
Virus Activation
Premedication
Antibodies
Albuterol
Fluconazole
Tetanus
Lung Injury
Pharynx
Exanthema
Cough
Hepatitis B virus
Dyspnea
Arthritis
Immunoglobulins
Immunization
Reference Values

Keywords

  • nephrotic syndrome
  • ofatumumab
  • rituximab
  • side effects

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome. / Bonanni, Alice; Calatroni, Marta; D'Alessandro, Matteo; Signa, Sara; Bertelli, Enrica; Cioni, Michela; Di Marco, Eddi; Biassoni, Roberto; Caridi, Gianluca; Ingrasciotta, Giulia; Bertelli, Roberta; Di Donato, Armando; Bruschi, Maurizio; Canepa, Alberto; Piaggio, Giorgio; Ravani, Pietro; Ghiggeri, Gian Marco.

In: British Journal of Clinical Pharmacology, Vol. 84, No. 6, 01.06.2018, p. 1238-1249.

Research output: Contribution to journalArticle

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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.",
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T1 - Adverse events linked with the use of chimeric and humanized anti-CD20 antibodies in children with idiopathic nephrotic syndrome

AU - Bonanni, Alice

AU - Calatroni, Marta

AU - D'Alessandro, Matteo

AU - Signa, Sara

AU - Bertelli, Enrica

AU - Cioni, Michela

AU - Di Marco, Eddi

AU - Biassoni, Roberto

AU - Caridi, Gianluca

AU - Ingrasciotta, Giulia

AU - Bertelli, Roberta

AU - Di Donato, Armando

AU - Bruschi, Maurizio

AU - Canepa, Alberto

AU - Piaggio, Giorgio

AU - Ravani, Pietro

AU - Ghiggeri, Gian Marco

PY - 2018/6/1

Y1 - 2018/6/1

N2 - 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.

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