Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial.
glomerulonephritis
membranous nephropathy
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:
Apr 2021
Apr 2021
Historique:
received:
28
07
2020
accepted:
22
12
2020
pubmed:
3
3
2021
medline:
3
3
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking. We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events. At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen. This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial. Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535.
Sections du résumé
BACKGROUND
BACKGROUND
A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking.
METHODS
METHODS
We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events.
RESULTS
RESULTS
At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen.
CONCLUSIONS
CONCLUSIONS
This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial.
CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER
UNASSIGNED
Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535.
Identifiants
pubmed: 33649098
pii: 00001751-202104000-00021
doi: 10.1681/ASN.2020071091
pmc: PMC8017548
doi:
Banques de données
ClinicalTrials.gov
['NCT03018535']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
972-982Investigateurs
Francesco Scolari
(F)
Elisa Delbarba
(E)
Domenico Santoro
(D)
Loreto Gesualdo
(L)
Paolo Protopapa
(P)
Lucia Argentiero
(L)
Antonello Pani
(A)
Andrea Angioi
(A)
Nicola Lepore
(N)
Nadia Dallera
(N)
Laila-Yasmin Mani
(LY)
Bruno Vogts
(B)
Marisa Santostefano
(M)
Sandro Feriozzi
(S)
Marco Quaglia
(M)
Giuliano Boscutti
(G)
Angelo Ferrantelli
(A)
Carmelita Marcantoni
(C)
Patrizia Passerini
(P)
Riccardo Magistroni
(R)
Federico Alberici
(F)
Gian Marco Ghiggeri
(GM)
Claudio Ponticelli
(C)
Pietro Ravani
(P)
Informations de copyright
Copyright © 2021 by the American Society of Nephrology.
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