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

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 reported data on side effects related to the use of rituximab (a chimeric anti-body; 130 pts) and ofatumumab (a humanized anti-body; 37 pts) in children with INS (steroid-dependent and steroid/calcineurin-inhibitor dependent disease) treated in a national referral center during a 9-year period (400 treatments; follow-up 1-9 years).

Results

Infusion reactions were materially absent in children with steroid-dependent disease. Rash, dyspnea, fever, cough and itchy throat (5% and 18% following rituximab and ofatumumab infusion) were resolved with 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, etc.). Circulating CD19/20 fell to 0 at month one and were reconstituted at month 3; circulating IgGs remained within the normal range for one year. Anti-tetanus and anti-HBV immunization was not modified by either treatment; EBV and JCV activation markers were occasionally observed.

Conclusion

Overall, 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 support their use as steroid-sparing agents in children with INS.

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