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

作者：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

来源：British Journal of Clinical Pharmacology, 2018, 84(6): 1238-1249.

DOI：10.1111/bcp.13548

• nephrotic syndrome
• ofatumumab
• rituximab
• side effects

AimsAnti-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.
MethodsWe 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 1-9years).
ResultsInfusion 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 3months), including arthritis (2%) and lung injury (1%), were more common with rituximab. Infections were observed 3-9months 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 1year. Tetanus and hepatitis B virus immunization was not modified by either treatment; Epstein-Barr virus and John Cunningham virus activation markers were occasionally observed.
ConclusionOverall, 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.

• 出版日期2018-6