Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study

Snehamayee Nayak; Rina Tripathy; Subal Kumar Pradhan

doi:doi:10.11648/j.ajp.20220801.16

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Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study

Snehamayee Nayak, Rina Tripathy, Subal Kumar Pradhan

Published in American Journal of Pediatrics (Volume 8, Issue 1)

Received: 6 December 2021 Accepted: 21 December 2021 Published: 28 January 2022

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Abstract

Corticosteroids have been the main treatment of nephrotic syndrome (NS) for decades however many patients fail to respond. In such children, alternative immunosuppressive medications such as rituximab is used to maintain remission of NS. However, antibodies to rituximab develops during treatment reduces its efficacy. Therefore, this study aimed to measure anti-rituximab antibody (ARA) levels and efficacy of rituximab in children treated for NS. This prospective observational study was conducted among children with difficult to treat nephrotic syndrome. After baseline assessment, patients received single dose of intravenous infusion of 375 mg/m² rituximab. ARA levels were determined at base line, 3-month, 6-month, and 12-month interval. Thirty-four patients with a mean age of 7 years were evaluated in this study. During follow up visits five patients developed ARA; two patients detected ARA of 23.7 IU/ µL at 3-month, one patient had ARA level of 53.2 IU/µL at 6-month and during last follow up visit (at 12 month) two patients had mean ARA level of 24.1 IU/µL. The number of relapses per person year before rituximab was 1.5 (Incidence density) which changed to 0.14 per person year after the rituximab administration in the study subjects. Twenty-Nine patients became relapse-free during rituximab treatment. Out of five patients with ARA, one had relapse during follow up. There was no major adverse effect observed during and post-rituximab therapy. In conclusion, the study demonstrated ARA levels in few patients who were treated with rituximab having sustained clinical outcomes without any major adverse events.

Published in	American Journal of Pediatrics (Volume 8, Issue 1)
DOI	10.11648/j.ajp.20220801.16
Page(s)	23-29
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Anti-Rituximab Antibody, Rituximab, CD-19, Nephrotic Syndrome, Relapse

References

[1]	Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. The Lancet 2018; 392 (10141): 61-74.
[2]	Haffner D, Fischer DC. Nephrotic syndrome and rituximab: facts and perspectives. Pediatr Nephrol 2009; 24 (8): 1433-8.
[3]	Tellier S, Brochard K, Garnier A, Bandin F, Llanas B, Guigonis V, et al. Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome. Pediatr Nephrol 2013; 28: 911-8.
[4]	Guigonis V, Dallocchio A, Baudouin V, Dehennault M, Hachon-Le Camus C, Afanetti M, et al. Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases. Pediatr Nephro 2008; 23: 1269-79.
[5]	Sellier-Leclerc AL, Macher MA, Loirat C, Guerin V, Watier H, Peuchmaur M, et al. Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 2010; 25: 1109-15.
[6]	Kamei K, Ishikura K, Sako M, Aya K, Tanaka R, Nozu K, et al. Long-term outcome of childhood-onset complicated nephrotic syndrome after a multicenter, double-blind, randomized, placebo-controlled trial of rituximab. Pediatr Nephrol 2017; 32 (11): 2071-8.
[7]	Schmidt E, Hennig K, Mengede C, Zillikens D, Kromminga A. Immunogenicity of rituximab in patients with severe pemphigus. Clin Immunol 2009; 132 (3): 334-41.
[8]	Ahn YH, Kang HG, Lee JM, Choi HJ, Ha IS, Cheong HI. Development of antirituximab antibodies in children with nephrotic syndrome. Pediatr Nephrol 2014; 29 (8): 1461-4.
[9]	Lunardon L, Payne AS. Inhibitory human antichimeric antibodies to rituximab in a patient with pemphigus. J Allergy Clin Immunol 2012; 130 (3): 800-3.
[10]	Ravani P, Rossi R, Bonanni A, Quinn RR, Sica F, Bodria M, et al. Rituximab in children with steroid-dependent nephrotic syndrome: A multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol 2015; 26 (9): 2259-66.
[11]	Ruggenenti P, Ruggiero B, Cravedi P, Vivarelli M, Massella L, Marasà M, et al. Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. J Am Soc Nephrol 2014; 25 (4): 850-63.
[12]	Teisseyre M, Boyer-Suavet S, Crémoni M, Brglez V, Esnault V, Seitz-Polski B. Analysis and management of rituximab resistance in PLA2R1-associated membranous nephropathy. Kidney Int Rep 2021; 6 (4): 1183-8.
[13]	Cornec D, Tempescul A, Querellou S, Hutin P, Pers JO, Jamin C, et al. Identification of patients with indolent B cell lymphoma sensitive to rituximab monotherapy. Ann Hematol 2012; 91 (5): 715-21.
[14]	Keystone E, Fleischmann R, Emery P, Furst DE, van Vollenhoven R, Bathon J, et al. Safety and efficacy of additional courses of rituximab in patients with active rheumatoid arthritis: an open-label extension analysis. Arthritis Rheum 2007; 56 (12): 3896-908.
[15]	Looney RJ, Anolik JH, Campbell D, Felgar RE, Young F, Arend LJ, et al. B cell depletion as a novel treatment for systemic lupus erythematosus: a phase I/II dose-escalation trial of rituximab. Arthritis Rheum 2004; 50 (8): 2580-9.
[16]	Boyer-Suavet S, Andreani M, Lateb M, Savenkoff B, Brglez V, Benzaken S, et al. Neutralizing Anti-Rituximab Antibodies and Relapse in Membranous Nephropathy Treated With Rituximab. Front Immunol 2020; 10: 3069.
[17]	Fujinaga S, Nishino T, Endo S, Umeda C, Watanabe Y, Nakagawa M. Unfavorable impact of Anti-Rituximab antibodies on clinical outcomes in children with complicated steroid-dependent nephrotic syndrome. Pediatr Nephrol 2020; 35 (10): 2003-8.
[18]	Fujinaga S, Nishino T. Is cytokine-release syndrome the cause of rituximab treatment-related infusion reactions in children with nephrotic syndrome? Impact of Anti-Rituximab antibodies. Pediatr Nephrol 2018; 33 (6): 1097-8.
[19]	Albert D, Dunham J, Khan S, Stansberry J, Kolasinski S, Tsai D, et al. Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus. Ann Rheum Dis 200; 67: 1724-31.
[20]	Bennett CL. Pharmacovigilance and PML in the oncology setting. Cleve Clin J Med 2011; 78 (2): S13-7.
[21]	Fervenza FC, Cosio FG, Erickson SB, Specks U, Herzenberg AM, Dillon JJ, et al. Rituximab treatment of idiopathic membranous nephropathy. Kidney Int 2008; 73 (1): 117-25.

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APA Style

Snehamayee Nayak, Rina Tripathy, Subal Kumar Pradhan. (2022). Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study. American Journal of Pediatrics, 8(1), 23-29. https://doi.org/10.11648/j.ajp.20220801.16

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ACS Style

Snehamayee Nayak; Rina Tripathy; Subal Kumar Pradhan. Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study. Am. J. Pediatr. 2022, 8(1), 23-29. doi: 10.11648/j.ajp.20220801.16

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AMA Style

Snehamayee Nayak, Rina Tripathy, Subal Kumar Pradhan. Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study. Am J Pediatr. 2022;8(1):23-29. doi: 10.11648/j.ajp.20220801.16

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@article{10.11648/j.ajp.20220801.16,
  author = {Snehamayee Nayak and Rina Tripathy and Subal Kumar Pradhan},
  title = {Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study},
  journal = {American Journal of Pediatrics},
  volume = {8},
  number = {1},
  pages = {23-29},
  doi = {10.11648/j.ajp.20220801.16},
  url = {https://doi.org/10.11648/j.ajp.20220801.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20220801.16},
  abstract = {Corticosteroids have been the main treatment of nephrotic syndrome (NS) for decades however many patients fail to respond. In such children, alternative immunosuppressive medications such as rituximab is used to maintain remission of NS. However, antibodies to rituximab develops during treatment reduces its efficacy. Therefore, this study aimed to measure anti-rituximab antibody (ARA) levels and efficacy of rituximab in children treated for NS. This prospective observational study was conducted among children with difficult to treat nephrotic syndrome. After baseline assessment, patients received single dose of intravenous infusion of 375 mg/m2 rituximab. ARA levels were determined at base line, 3-month, 6-month, and 12-month interval. Thirty-four patients with a mean age of 7 years were evaluated in this study. During follow up visits five patients developed ARA; two patients detected ARA of 23.7 IU/ µL at 3-month, one patient had ARA level of 53.2 IU/µL at 6-month and during last follow up visit (at 12 month) two patients had mean ARA level of 24.1 IU/µL. The number of relapses per person year before rituximab was 1.5 (Incidence density) which changed to 0.14 per person year after the rituximab administration in the study subjects. Twenty-Nine patients became relapse-free during rituximab treatment. Out of five patients with ARA, one had relapse during follow up. There was no major adverse effect observed during and post-rituximab therapy. In conclusion, the study demonstrated ARA levels in few patients who were treated with rituximab having sustained clinical outcomes without any major adverse events.},
 year = {2022}
}

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TY - JOUR
T1 - Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study
AU - Snehamayee Nayak
AU - Rina Tripathy
AU - Subal Kumar Pradhan
Y1 - 2022/01/28
PY - 2022
N1 - https://doi.org/10.11648/j.ajp.20220801.16
DO - 10.11648/j.ajp.20220801.16
T2 - American Journal of Pediatrics
JF - American Journal of Pediatrics
JO - American Journal of Pediatrics
SP - 23
EP - 29
PB - Science Publishing Group
SN - 2472-0909
UR - https://doi.org/10.11648/j.ajp.20220801.16
AB - Corticosteroids have been the main treatment of nephrotic syndrome (NS) for decades however many patients fail to respond. In such children, alternative immunosuppressive medications such as rituximab is used to maintain remission of NS. However, antibodies to rituximab develops during treatment reduces its efficacy. Therefore, this study aimed to measure anti-rituximab antibody (ARA) levels and efficacy of rituximab in children treated for NS. This prospective observational study was conducted among children with difficult to treat nephrotic syndrome. After baseline assessment, patients received single dose of intravenous infusion of 375 mg/m2 rituximab. ARA levels were determined at base line, 3-month, 6-month, and 12-month interval. Thirty-four patients with a mean age of 7 years were evaluated in this study. During follow up visits five patients developed ARA; two patients detected ARA of 23.7 IU/ µL at 3-month, one patient had ARA level of 53.2 IU/µL at 6-month and during last follow up visit (at 12 month) two patients had mean ARA level of 24.1 IU/µL. The number of relapses per person year before rituximab was 1.5 (Incidence density) which changed to 0.14 per person year after the rituximab administration in the study subjects. Twenty-Nine patients became relapse-free during rituximab treatment. Out of five patients with ARA, one had relapse during follow up. There was no major adverse effect observed during and post-rituximab therapy. In conclusion, the study demonstrated ARA levels in few patients who were treated with rituximab having sustained clinical outcomes without any major adverse events.
VL - 8
IS - 1
ER -

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Author Information

Snehamayee Nayak

Department of Paediatric, SVP Post Graduate Institute of Paediatrics and SCB Medical College, Cuttack, India
Rina Tripathy

Department of Biochemistry, SVP Post Graduate Institute of Paediatrics and SCB Medical College, Cuttack, India
Subal Kumar Pradhan

Division of Pediatric Nephrology, SVP Post Graduate Institute of Paediatrics and SCB Medical College, Cuttack, India

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APA Style

Snehamayee Nayak, Rina Tripathy, Subal Kumar Pradhan. (2022). Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study. American Journal of Pediatrics, 8(1), 23-29. https://doi.org/10.11648/j.ajp.20220801.16

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ACS Style

Snehamayee Nayak; Rina Tripathy; Subal Kumar Pradhan. Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study. Am. J. Pediatr. 2022, 8(1), 23-29. doi: 10.11648/j.ajp.20220801.16

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AMA Style

Snehamayee Nayak, Rina Tripathy, Subal Kumar Pradhan. Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study. Am J Pediatr. 2022;8(1):23-29. doi: 10.11648/j.ajp.20220801.16

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@article{10.11648/j.ajp.20220801.16,
  author = {Snehamayee Nayak and Rina Tripathy and Subal Kumar Pradhan},
  title = {Anti-Rituximab Antibodies in Idiopathic Nephrotic Children Treated with Rituximab: A Prospective Single Centre Study},
  journal = {American Journal of Pediatrics},
  volume = {8},
  number = {1},
  pages = {23-29},
  doi = {10.11648/j.ajp.20220801.16},
  url = {https://doi.org/10.11648/j.ajp.20220801.16},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajp.20220801.16},
  abstract = {Corticosteroids have been the main treatment of nephrotic syndrome (NS) for decades however many patients fail to respond. In such children, alternative immunosuppressive medications such as rituximab is used to maintain remission of NS. However, antibodies to rituximab develops during treatment reduces its efficacy. Therefore, this study aimed to measure anti-rituximab antibody (ARA) levels and efficacy of rituximab in children treated for NS. This prospective observational study was conducted among children with difficult to treat nephrotic syndrome. After baseline assessment, patients received single dose of intravenous infusion of 375 mg/m2 rituximab. ARA levels were determined at base line, 3-month, 6-month, and 12-month interval. Thirty-four patients with a mean age of 7 years were evaluated in this study. During follow up visits five patients developed ARA; two patients detected ARA of 23.7 IU/ µL at 3-month, one patient had ARA level of 53.2 IU/µL at 6-month and during last follow up visit (at 12 month) two patients had mean ARA level of 24.1 IU/µL. The number of relapses per person year before rituximab was 1.5 (Incidence density) which changed to 0.14 per person year after the rituximab administration in the study subjects. Twenty-Nine patients became relapse-free during rituximab treatment. Out of five patients with ARA, one had relapse during follow up. There was no major adverse effect observed during and post-rituximab therapy. In conclusion, the study demonstrated ARA levels in few patients who were treated with rituximab having sustained clinical outcomes without any major adverse events.},
 year = {2022}
}

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