Single dose of rituximab for refractory steroid-dependent nephrotic syndrome in children
We conducted a multicenter prospective trial to evaluate the efficacy, safety and pharmacokinetics of a single dose of rituximab (375 mg/m2 body surface area) for the treatment of children with refractory steroid-dependent nephrotic syndrome (SDNS). All patients (n = 12) were able to discontinue steroids at a median of 74 days after treatment. The frequency of relapses per 6 months was significantly reduced and the steroid-free period per 6 months was significantly increased after treatment compared with those before treatment. The condition in nine of the patients (75%) relapsed at a median of 129 days after treatment, and seven patients were given additional rituximab due to steroid dependency. Most of the relapses developed simultaneously with recovery of B-cells. However, three patients (25%) did not have a relapse with B-cell recovery and the disease was kept in remission for more than 1 year. None of the patients developed life-threatening adverse events. This is the first report of a prospective study of a single dose of rituximab for refractory SDNS. Treatment with a single dose of rituximab may be effective for refractory SDNS, but its efficacy to prevent relapses was transient in most of the patients.
KeywordsRefractory steroid-dependent nephrotic syndrome Children Clinical trial Rituximab Pharmacokinetics
This study was supported by the Health and Labor Sciences Research Grant for the Large Scale Clinical Trial Network Project (to K.I.). The authors are grateful to Professor Shuki Mizutani, Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, and the Zenyaku Corporation, for their helpful advice.
- 7.Kemper MJ, Möller K, Ludwig K, Rink N, Muller-Wiefel DE (2006) Rituximab in the treatment of refractory steroid-sensitive nephrotic syndrome (abstract). Pediatr Nephrol 21:1528Google Scholar
- 8.Dallachio IA, Trimoreau F, Feuillard J, Guigoinis V (2006) A case of steroid-dependent nephrotic syndrome treated with rituximab (abstract). Pediatr Nephrol 21:1615Google Scholar
- 10.Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, Groothoff J, Llanas B, Niaudet P, Nivet H, Raynaud N, Taque S, Ronco P, Bouissou F (2008) Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephrol 23:269–279CrossRefGoogle Scholar
- 15.Tabata K, Yamaoka K, Kaibara A, Suzuki S, Terakawa M, Hata T (1999) Moment analysis program available on Microsoft Excel. Xenobiot Metab Dispos 14:286–293Google Scholar
- 16.Vieira CA, Agarwal A, Book BK, Sidner RA, Bearden CM, Gebel HM, Roggero AL, Fineberg NS, Taber T, Kraus MA, Pescovitz MD (2004) Rituximab for reduction of anti-HLA antibodies in patients awaiting renal transplantation: 1. Safety, pharmacodynamics, and pharmacokinetics. Transplantation 77:542–548PubMedCrossRefGoogle Scholar
- 17.Berinstein NL, Grillo-López AJ, White CA, Bence-Bruckler I, Maloney D, Czuczman M, Green D, Rosenberg J, McLaughlin P, Shen D (1998) Association of serum rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol 9:995–1001PubMedCrossRefGoogle Scholar
- 19.Tobinai K, Kobayashi Y, Narabayashi M, Ogura M, Kagami Y, Morishima Y, Ohtsu T, Igarashi T, Sasaki Y, Kinoshita T, Murate T (1998) Feasibility and pharmacokinetic study of a chimeric anti-CD20 monoclonal antibody (IDEC-C2B8, rituximab) in relapsed B-cell lymphoma. The IDEC-C2B8 Study Group. Ann Oncol 9:527–534PubMedCrossRefGoogle Scholar
- 20.Iacona I, Lazzarino M, Avanzini MA, Rupolo M, Arcaini L, Astori C, Lunghi F, Orlandi E, Morra E, Zagonel V, Regazzi MB (2000) Rituximab (IDEC-C2B8): validation of a sensitive enzyme-linked immunoassay applied to a clinical pharmacokinetic study. Ther Drug Monit 22:295–301PubMedCrossRefGoogle Scholar
- 21.Regazzi MB, Iacona I, Avanzini MA, Rupolo M, Arcaini L, Astori C, Lunghi F, Orlandi E, Morra E, Zagonel V, Regazzi MB (2005) Pharmacokinetic behavior of rituximab: a study of different schedules of administration for heterogeneous clinical settings. Ther Drug Monit 27:785–792PubMedCrossRefGoogle Scholar
- 27.Tokunaga M, Saito K, Kawabata D, Imura Y, Fujii T, Nakayamada S, Tsujimura S, Nawata M, Iwata S, Azuma T, Mimori T, Tanaka Y (2007) Efficacy of rituximab (anti-CD20) for refractory systemic lupus erythematosus involving the central nervous system. Ann Rheum Dis 66:470–475PubMedCrossRefGoogle Scholar