Eugene Yu-hin Chan, Chun Ting Au, Ellen L.M. Yu, Andrea Angeletti, Zainab Arslan, Olivia Boyer, Chang‐Yien Chan, Manuela Colucci, Guillaume Dorval, Claire Dossier, Gian Marco Ghiggeri, Riku Hamada, Julien Hogan, Kenji Ishikura, Koichi Kamei, Markus J. Kemper, Alison Lap-tak Ma, Rulan S. Parekh, Seetha Radhakrishnan, Cal Robinson, Qian Shen, Rajiv Sinha, Chantida Subun, Sharon Teo, Marina Vivarelli, Hazel Webb, Hong Xu, Tomohiko Yamamura, Hui Kim Yap, Kjell Tullus
Background Efficacy and safety of rituximab in children under 6 years with frequently-relapsing and/or steroid-dependent nephrotic syndrome (FRSDNS) remain controversial. Methods We conducted a retrospective cohort study at 16 paediatric nephrology centres from 10 countries in Asia, Europe and North America. We first analysed young children with FRSDNS who received first rituximab before 6 years. As a secondary analysis, we matched young children <6 years with older patients who received first rituximab between 6-21 years. Results One-hundred-and-one children (70 boys) received the first rituximab courses at 4.5 years old (IQR, 3.6-5.4), with an observation period of 4.6 years (IQR, 3.2-6.6). Most children were Europeans (42%) and Southeast Asians (35%). Seventy-five children (74%) were multidrug-dependent. In primary analysis, among the 101 young children, median relapse-free survival after first rituximab was 8.8 months (95% CI, 7.5-11.0) by Kaplan-Meier analysis. Each additional month of concurrent immunosuppression post-rituximab reduced relapse risk by 7% (HR adj 0.93; 95% CI, 0.89-0.96; p<0.001). An increase age upon rituximab trended towards lower relapse risk (HR adj 0.76/ year ; 95% CI, 0.57-1.03; p=0.07). Annual relapse rate reduced from 3 (IQR, 2-4) to 1 (IQR, 0-1) following rituximab (p<0.0001). Rituximab was repeated in 85 children (84%), mostly due to relapses. Leading adverse events were hypogammaglobulinaemia (n=30/53, 57%), neutropenia (n=9/97, 9%), and infection (n=8/115, 8%). Baseline low IgG levels were associated with hypogammaglobulinaemia post-rituximab. All except one child had normal kidney function at last follow-up. In the secondary analysis (70 young vs 70 older children), although insignificant, younger children showed a trend of earlier relapse (8.3 vs 11.3 months; log-rank test p=0.14), and more complications (hypogammaglobulinaemia, 63% vs 57%; p=0.01; neutropenia, 13% vs 7%; infection, 9% vs 4%). Conclusion Rituximab offers reasonable efficacy in young children with FRSDNS, with a trend of shorter relapse-free period and more potential complications. Rituximab should be reserved until established treatments are exhausted.