Abstract：Objective To study the efficacy and safety of repeated application of rituximab (RTX) at a low dose (200 mg/m2) versus the recommended dose (375 mg/m2) for remission maintenance in frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Methods A randomized controlled trial was conducted for 29 children with FRNS/SDNS who received systemic treatment in the Department of Nephrology, Anhui Provincial Children's Hospital, from September 2020 to December 2021. These children were divided into a recommended dose group (n=14) and a low dose group (n=15) using a random number table. The two groups were compared in terms of general characteristics, changes in CD19 expression after RTX treatment, number of relapses, glucocorticoid dose, adverse reactions of RTX, and hospital costs. Results After RTX treatment, both the low dose group and the recommended dose group achieved B-lymphocyte depletion and had significant reductions in the number of relapses and glucocorticoid dose (P<0.05). The low dose group had a comparable clinical effect to the recommended dose group after RTX treatment (P>0.05), and the low dose group had a significant reduction in hospital costs for the second, third, and fourth times of hospitalization (P<0.05). There were no serious adverse reactions in either group during RTX treatment and late follow-up, and there was no significant difference in adverse reactions between the two groups (P>0.05). Conclusions Repeated RTX treatment at a low dose has comparable clinical efficacy and safety to that at the recommended dose and can significantly reduce the number of FRNS/SDNS relapses and the amount of glucocorticoids used, with little adverse effect throughout the treatment cycle. Therefore, it holds promise for clinical application.
ZHU Ying,WU Ling,WANG Yun et al. Efficacy and safety of low-dose rituximab in treatment of pediatric nephrotic syndrome: a prospective randomized controlled trial[J]. CJCP, 2023, 25(6): 606-611.
Iijima K, Sako M, Oba M, et al. Mycophenolate mofetil after rituximab for childhood-onset complicated frequently-relapsing or steroid-dependent nephrotic syndrome[J]. J Am Soc Nephrol, 2022, 33(2): 401-419. PMID: 34880074. PMCID: PMC8819987. DOI: 10.1681/ASN.2021050643.
Basu B, Preussler S, Sander A, et al. Randomized clinical trial to compare efficacy and safety of repeated courses of rituximab to single-course rituximab followed by maintenance mycophenolate-mofetil in children with steroid dependent nephrotic syndrome[J]. BMC Nephrol, 2020, 21(1): 520. PMID: 33256621. PMCID: PMC7706288. DOI: 10.1186/s12882-020-02153-5.
Nagano C, Sako M, Kamei K, et al. Study protocol: multicenter double-blind, randomized, placebo-controlled trial of rituximab for the treatment of childhood-onset early-stage uncomplicated frequently relapsing or steroid-dependent nephrotic syndrome (JSKDC10 trial)[J]. BMC Nephrol, 2019, 20(1): 293. PMID: 31375087. PMCID: PMC6679488. DOI: 10.1186/s12882-019-1470-3
Chan EY, Webb H, Yu E, et al. Both the rituximab dose and maintenance immunosuppression in steroid-dependent/frequently-relapsing nephrotic syndrome have important effects on outcomes[J]. Kidney Int, 2020, 97(2): 393-401. PMID: 31874801. DOI: 10.1016/j.kint.2019.09.033.
Kamei K, Ishikura K, Sako M, et al. Long-term outcome of childhood-onset complicated nephrotic syndrome after a multicenter, double-blind, randomized, placebo-controlled trial of rituximab[J]. Pediatr Nephrol, 2017, 32(11): 2071-2078. PMID: 28664242. DOI: 10.1007/s00467-017-3718-0.
Hogan J, Dossier C, Kwon T, et al. Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome[J]. Pediatr Nephrol, 2019, 34(2): 253-259. PMID: 30109447. DOI: 10.1007/s00467-018-4052-x.
Sellier-Leclerc AL, Baudouin V, Kwon T, et al. Rituximab in steroid-dependent idiopathic nephrotic syndrome in childhood—follow-up after CD19 recovery[J]. Nephrol Dial Transplant, 2012, 27(3):1083-1089. PMID: 21810762. DOI: 10.1093/ndt/gfr405.
Chan EY, Yu ELM, Angeletti A, et al. Long-term efficacy and safety of repeated rituximab to maintain remission in idiopathic childhood nephrotic syndrome: an international study[J]. J Am Soc Nephrol, 2022, 33(6): 1193-1207. PMID: 35354600. PMCID: PMC9161790. DOI: 10.1681/ASN.2021111472.
15 Chen Y, Shen Q, Dong M, et al. Population pharmacokinetics of rituximab in pediatric patients with frequent-relapsing or steroid-dependent nephrotic syndrome[J]. 2021, 12: 725665. PMID: 34539407. PMCID: PMC8443776. DOI: 10.3389/fphar.2021.725665.
Luciani L, Ninove L, Zandotti C, et al. Fatal underhanded chronic enterovirus infection associated with anti-CD20 monotherapy for central nervous system demyelinating disease[J]. Mult Scler, 2021, 27(2): 320-323. PMID: 32584194. DOI: 10.1177/1352458520923978.
