Published online May 6, 2019. doi: 10.12998/wjcc.v7.i9.1021
Peer-review started: February 26, 2019
First decision: March 10, 2019
Revised: March 20, 2019
Accepted: April 9, 2019
Article in press: April 9, 2019
Published online: May 6, 2019
It has been shown in paediatric patients with complicated nephrotic syndrome (NS) that rituximab (RTX) administration can induce persistent IgG hypogammaglobulinemia among subjects showing low basal IgG levels.
RTX is an effective and safe treatment for childhood-onset, complicated, frequently relapsing, and steroid-dependent NS. Data about long-term safety are limited. Evidence on the impact of RTX treatment on IgG levels in children with complicated NS having normal baseline IgG levels are limited to a few cases for each available study. Here, we aimed to provide further evidence about RTX safety in childhood and provide a way for possible future perspective multi-centre studies about this topic.
The aim of our study was to evaluate the effect of RTX on IgG levels and infections in patients with complicated, frequently relapsing, and steroid- and cyclosporine-dependent NS with normal baseline IgG levels.
We consecutively enrolled all patients with complicated NS and normal basal IgG levels undergoing the first RTX infusion from January 2008 to January 2016. Basal IgG levels were dosed after 6 wk of absent proteinuria and with a maximal interval of 3 mo before RTX infusion. The primary outcome was the onset of IgG hypogammaglobulinemia during the follow-up according to IgG normal values for age (mean ± SD).
We enrolled 20 patients with a mean age at NS diagnosis of 4.2 ± 3.3 years. The mean age at the first RTX infusion was 10.9 ± 3.5 years. Eleven out of twenty patients (55%) developed IgG hypogammaglobulinemia. None of these patients showed severe or recurrent infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion. Three patients undergoing only the two “starting doses” experienced normalization of IgG levels. When comparing patients showing and not showing IgG hypogammaglobulinemia, no differences were found in the utilization of corticosteroids, cyclosporine, cyclophosphamide, other immunosuppressive agents, and more than one immunosuppressive agent. A non-significant trend showing a lower number of relapses after RTX infusion and younger age at first RTX infusion for the patients presenting IgG hypogammaglobulinemia compared with the patients not presenting IgG hypogammaglobulinemia was present. Using Kaplan-Meier analysis, the cumulative proportion of patients free of IgG hypogammaglobulinemia was 57.8% after the first RTX dose, 51.5% after the third, 44.1% after the fourth, and 35.5% after the fifth dose.
Our study is the first study specifically designed to enrol only children with complicated, frequently relapsing, and steroid- and cyclosporine-dependent NS with normal basal IgG levels. Our case series shows that RTX can induce IgG hypogammaglobulinemia in patients with pre-RTX IgG normal values and that persisting post-RTX IgG hypogammaglobulinemia could be dose-dependent. None of the patients developing IgG hypogammaglobulinemia showed severe infections. Only one patient suffered from recurrent acute otitis media and underwent substitutive IgG infusion.
This article adds to our knowledge about the safety of RTX in children with complicated NS. Future studies should prospectively collect multicentre data on the effects of RTX on IgG levels and risk of severe infections. This will improve management of post-RTX IgG hy-pogammaglobulinemia and help define patients who could benefit from substitutive IgG infusion.