P0401RITUXIMAB VESUS CYCLOPHOSPHAMIDE AS FIRST STEROID SPARING AGENT IN CHILDHOOD FREQUENTLY RELAPSING OR STEROID DEPENDENT NEPHROTIC SYNDROME

Abstract Background and Aims Approximately 50% of children with steroid sensitive nephrotic syndrome (SSNS) will suffer from frequent relapses or steroid dependency, prompting the use of so-called steroid-sparing drugs. In this pilot study, we compare the efficacy and safety of rituximab to oral cyclophosphamide as first-line steroid-sparing medications Method A prospective open label randomized study of children with frequent relapsing or steroid-dependant SSNS. Exclusion criteria were steroid-resistant disease, prescription of immunosuppressive agents other than prednisolone or levamisole, evidence of impaired kidney function, leucopenia or active infection. The recruited children were allocated either to the oral cyclophosphamide (3mg/kg/day for 8 weeks) or intravenous rituximab treatment (two doses of 375 mg/m2/dose, 2 weeks apart) and were monitored for relapses and side effects for 12 months Results 46 subjects were included from two centers; 27 received cyclophosphamide and 19 received rituximab. One-year relapse-free survival was reached in 17 (58.6%) patients treated with cyclophosphamide compared to 16 (84.2%) with rituximab (adjusted HR: 0.36; 95% CI: 0.09 – 1.45; p=0.151). The mean interval to relapse was 6.9 months in the cyclophosphamide group (N=10) and 6.3 months in the rituximab group (N=3). Both treatments were associated with a significant (p=?) reduction in prescribed dose of oral alternate days steroid from 1.02 to 0.36mg/kg (Cyclophoshamide) and 0.86 to 0.08mg/kg (Rituximab). Importantly, a significantly (P = 0.003) higher percentage of patients achieved complete withdrawal of steroid within 3 months of commencing study treatment in the rituximab (73.7%) versus cyclophosphamide (29.6%) group. Transient leucopenia was the most frequent adverse effect observed in the cyclophosphamide group (18.5%) and one patient (3.4%) had acute hepatotoxicity beside severe leucopenia and neutropenia on the 7th week of treatment although she showed complete recovery with withdrawal of cyclophosphamide and maintained remission. A minor infusion related reaction was observed in 1 patient (5%) in the rituximab group. Conclusion Rituximab is non-inferior to cyclophosphamide and safe as a first-line steroid-sparing agent in children with SSNS. A larger multicenter study is required to assess superiority over cyclophosphamide