Repeated administration of rituximab for refractory nephroticsyndrome in children

Abstract

Objective: Recently, several non-controlled clinical trials have suggested that rituximab (RTX), a chimeric monoclonal antibody inhibiting CD20-mediated B-cell proliferation and differentiation, is effective for children with refractory nephrotic syndrome (NS), though an established regimen does not exist. An investigation into refractory NS reported the peripheral blood B-cell count to decrease for about 100days upon single RTX administration, before NS relapsed. This study was conducted to clarify whether long-term remission of refractory NS may be obtained by repeated administration of RTX and maintaining a decreased peripheral blood B-cell count. Method(s): RTX at 375mg/m2/time was repeatedly administered every 3 months, a total of 4 times to 5 children with steroid-dependent NS; then, the clinical indicators before and after administration were compared by the Wilcoxon signed-rank test. Result(s): The median age at the start of RTX administration (range) was 14 (10-17) years old. Regarding the renal tissue, minor changes were seen in 4 cases, with 1 case of focal segmental glomerulosclerosis. The median (range) observation period was 6.3 (0.9-8.4) years before RTX administration and 2.9 (1.4-3.4) years following commencement of RTX administration. The changes in the clinical indicators before and after RTX administration were as follows {median value (range)}: (1) Annual number of relapses: before administration: 1.4 (1.1-3.5) times/year, after administration: 0.0 (0.0-0.3) times/year; (2) Steroid dosage: before administration: 0.80 (0.23-0.96) mg/kg/day, after administration: 0.03 (0.02-0.27) mg/kg/day; (3) Peripheral blood B-cell count: before administration: 196 (94.6-371) count/mul, during administration: 2.72 (0.920-116) count/mul, with all items significantly declining compared to before RTX administration (p<0.05). Relapse occurred in 2 cases following the start of RTX (period from starting RTX to relapse was 2.2 years and 1.9 years, respectively). No serious side effects or infectious diseases were seen. Conclusion(s): Repeated administration of RTX against refractory NS in children may be a useful therapeutic option.