Human or Chimeric Monoclonal Anti-CD20 Antibodies for Children with Nephrotic Syndrome: A Superiority Randomized Trial.
Adolescent
Anti-Inflammatory Agents
/ therapeutic use
Antibodies, Monoclonal, Humanized
/ adverse effects
Antigens, CD20
/ immunology
B-Lymphocytes
Calcineurin Inhibitors
/ therapeutic use
Child
Chimera
Drug Therapy, Combination
Female
Humans
Immunoglobulin A
/ blood
Immunoglobulin G
/ blood
Immunologic Factors
/ adverse effects
Intention to Treat Analysis
Maintenance Chemotherapy
/ methods
Male
Nephrotic Syndrome
/ drug therapy
Prednisone
/ therapeutic use
Recurrence
Rituximab
/ adverse effects
Time Factors
antirituximab antibodies
calcineurin inhibitor-dependent nephrotic syndrome
glomerular disease
human anti-CD20 monoclonal antibodies
idiopathic nephrotic syndrome
memory B cells
ofatumumab
prediction of response
rituximab
steroid dependent nephrotic syndrome
Journal
Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836
Informations de publication
Date de publication:
10 2021
10 2021
Historique:
received:
27
04
2021
accepted:
20
06
2021
pubmed:
22
9
2021
medline:
15
12
2021
entrez:
21
9
2021
Statut:
ppublish
Résumé
The chimeric anti-CD20 monoclonal antibody rituximab is effective in steroid-dependent and calcineurin inhibitor-dependent forms of nephrotic syndrome, but many patients relapse at 1 year. Because ofatumumab, a fully human anti-CD20 monoclonal antibody, has a more extended binding site and higher affinity to CD20 compared with rituximab, it might offer superior efficacy in these patients. We designed a single-center randomized clinical trial to compare the long-term efficacy of ofatumumab versus rituximab in children and young adults with nephrotic syndrome maintained in remission with prednisone and calcineurin inhibitors. We randomized 140 children and young adults (aged 2-24 years) to receive intravenous ofatumumab (1.50 mg/1.73 m At 12 months, 37 of 70 (53%) participants who received ofatumumab experienced relapse versus 36 of 70 (51%) who received rituximab (odds ratio [OR], 1.06; 95% confidence interval [95% CI], 0.55 to 2.06). At 24 months, 53 of 70 (76%) participants who received ofatumumab experienced relapse, versus 46 of 70 (66%) who received rituximab (OR, 1.6; 95% CI, 0.8 to 3.3). The two groups exhibited comparable B cell subpopulation reconstitution and did not differ in adverse events. A single dose of ofatumumab was not superior to a single dose of rituximab in maintaining remission in children with steroid-dependent and calcineurin inhibitor-dependent nephrotic syndrome. ClinicalTrials.gov (NCT02394119) and https://www.clinicaltrialsregister.eu/ctr-search/search (2015-000624-28).
Sections du résumé
BACKGROUND
The chimeric anti-CD20 monoclonal antibody rituximab is effective in steroid-dependent and calcineurin inhibitor-dependent forms of nephrotic syndrome, but many patients relapse at 1 year. Because ofatumumab, a fully human anti-CD20 monoclonal antibody, has a more extended binding site and higher affinity to CD20 compared with rituximab, it might offer superior efficacy in these patients.
METHODS
We designed a single-center randomized clinical trial to compare the long-term efficacy of ofatumumab versus rituximab in children and young adults with nephrotic syndrome maintained in remission with prednisone and calcineurin inhibitors. We randomized 140 children and young adults (aged 2-24 years) to receive intravenous ofatumumab (1.50 mg/1.73 m
RESULTS
At 12 months, 37 of 70 (53%) participants who received ofatumumab experienced relapse versus 36 of 70 (51%) who received rituximab (odds ratio [OR], 1.06; 95% confidence interval [95% CI], 0.55 to 2.06). At 24 months, 53 of 70 (76%) participants who received ofatumumab experienced relapse, versus 46 of 70 (66%) who received rituximab (OR, 1.6; 95% CI, 0.8 to 3.3). The two groups exhibited comparable B cell subpopulation reconstitution and did not differ in adverse events.
CONCLUSIONS
A single dose of ofatumumab was not superior to a single dose of rituximab in maintaining remission in children with steroid-dependent and calcineurin inhibitor-dependent nephrotic syndrome.
CLINICAL TRIAL REGISTRATION NUMBERS
ClinicalTrials.gov (NCT02394119) and https://www.clinicaltrialsregister.eu/ctr-search/search (2015-000624-28).
Identifiants
pubmed: 34544820
pii: 00001751-202110000-00028
doi: 10.1681/ASN.2021040561
pmc: PMC8722811
doi:
Substances chimiques
Anti-Inflammatory Agents
0
Antibodies, Monoclonal, Humanized
0
Antigens, CD20
0
Calcineurin Inhibitors
0
Immunoglobulin A
0
Immunoglobulin G
0
Immunologic Factors
0
Rituximab
4F4X42SYQ6
ofatumumab
M95KG522R0
Prednisone
VB0R961HZT
Banques de données
ClinicalTrials.gov
['NCT02394119']
EudraCT
['2015–000624–28']
Types de publication
Comparative Study
Equivalence Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2652-2663Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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