Effect of different rituximab regimens on B cell depletion and time to relapse in children with steroid-dependent nephrotic syndrome
- 377 Downloads
Several studies have demonstrated that rituximab (RTX) improves relapse-free survival in patients with steroid-dependent nephrotic syndrome (SDNS). However, these studies used various RTX regimens and there are few data comparing these regimens in children with SDNS. In this retrospective study, we assessed the effect of three different initial RTX regimens on both time to B cell reconstitution and to first relapse.
Sixty-one SDNS patients receiving a first course of RTX were included. Group 1 received one injection of 100 mg/m2, group 2 received one injection of 375 mg/m2, and group 3 received two injections of 375 mg/m2 at day 0 and day 7. Time to B cell reconstitution and time to first relapse and respective risk factors were studied.
Median time to B cell reconstitution was 2.5 [1.8–3.5], 5.0 [3.9–6.0], and 6.6 [4.6–7.8] months in groups 1, 2, and 3, respectively. RTX regimen was associated with time to B cell reconstitution (HRs group 2 vs. 3, 4.07 [1.96–8.48]; group 1 vs. 3, 11.13 [4.04–30.67]). One-year relapse-free survival was 50% [58–77], 59% [42–76], and 72% [46–87] in groups 1, 2, and 3, respectively. RTX regimen was associated with risk of relapse (HRs group 2 vs. 3, 1.55 [0.51–4.65]; group 1 vs. 3, 4.98 [1.15–21.60]).
The initial dose of rituximab impacts time to B cell reconstitution and the probability of relapse. Risk of relapse is also associated with patient characteristics, suggesting that RTX regimen could be modified for each patient to balance efficacy, cost, and side effects.
KeywordsIdiopathic nephrotic syndrome Children B cell Rituximab
JHo and GD participated to the conception of the paper, to the analysis of the data, and the writing of the manuscript. CD, TK, MAM, AM, AC, ON, and VB participated to the data collection and to the writing of the manuscript. All the authors have revised the article and approved the final version.
Compliance with ethical standards
Ethics approval was granted through our institutional ethics committee.
Conflict of interest
The authors declare that they have no conflict of interest.
- 3.Pasini A, Aceto G, Ammenti A, Ardissino G, Azzolina V, Bettinelli A, Cama E, Cantatore S, Crisafi A, Conti G, D’Awgostino M, Dozza A, Edefonti A, Fede C, Groppali E, Gualeni C, Lavacchini A, Lepore M, Maringhini S, Mariotti P, Materassi M, Mencarelli F, Messina G, Negri A, Piepoli M, Ravaglia F, Simoni A, Spagnoletta L, Montini G, NefroKid Study Group (2015) Best practice guidelines for idiopathic nephrotic syndrome: recommendations versus reality. Pediatr Nephrol 30:91–101CrossRefGoogle Scholar
- 7.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 23:1269–1279CrossRefGoogle Scholar
- 9.Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y, Rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS) Study Group (2014) Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384:1273–1281CrossRefGoogle Scholar
- 10.Ravani P, Rossi R, Bonanni A, Quinn RR, Sica F, Bodria M, Pasini A, Montini G, Edefonti A, Belingheri M, De Giovanni D, Barbano G, Degl’Innocenti L, Scolari F, Murer L, Reiser J, Fornoni A, Ghiggeri GM (2015) Rituximab in children with steroid-dependent nephrotic syndrome: a multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol 26:2259–2266CrossRefGoogle Scholar
- 12.Kemper MJ, Gellermann J, Habbig S, Krmar RT, Dittrich K, Jungraithmayr T, Pape L, Patzer L, Billing H, Weber L, Pohl M, Rosenthal K, Rosahl A, Mueller-Wiefel DE, Dötsch J (2012) Long-term follow-up after rituximab for steroid-dependent idiopathic nephrotic syndrome. Nephrol Dial Transplant 27:1910–1915CrossRefGoogle Scholar
- 22.Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, Chianca A, Rubis N, Ene-Iordache B, Rudnicki M, Pollastro RM, Capasso G, Pisani A, Pennesi M, Emma F, Remuzzi G, Rituximab in Nephrotic Syndrome of Steroid-Dependent or Frequently Relapsing Minimal Change Disease Or Focal Segmental Glomerulosclerosis (NEMO) Study Group (2014) Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol 25:850–863CrossRefGoogle Scholar