Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy
AuthorFervenza, Fernando C
Appel, Gerald B
Barbour, Sean J
Rovin, Brad H
Lafayette, Richard A
Jefferson, Jonathan A
Gipson, Patrick E
Rizk, Dana V
Sedor, John R
Simon, James F
McCarthy, Ellen T
Lieske, John C
Thomas, Lesley F
Green, Dolly F
Juncos, Luis A
Blumenthal, Samuel S
Sussman, Amy N
Erickson, Stephen B
Canetta, Pietro A
Hebert, Lee A
Reich, Heather N
Parikh, Samir V
Gipson, Debbie S
Lee, Dominic K
da Costa, Bruno R
Cattran, Daniel C
MetadataShow full item record
PublisherMASSACHUSETTS MEDICAL SOC
CitationFervenza, F. C., Appel, G. B., Barbour, S. J., Rovin, B. H., Lafayette, R. A., Aslam, N., ... & Simon, J. F. (2019). Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. New England Journal of Medicine, 381(1), 36-46.
JournalNEW ENGLAND JOURNAL OF MEDICINE
Rights© 2019 Massachusetts Medical Society.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractBackground: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. Methods: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m(2) of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. Results: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P=0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A(2) receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P=0.06). Conclusions: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, .) In a randomized, controlled trial involving patients with membranous nephropathy, rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission for up to 24 months.
Note6 month embargo; published July 4, 2019
VersionFinal published version
SponsorsGenentech; Fulk Family Foundation
- A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR).
- Authors: Fervenza FC, Canetta PA, Barbour SJ, Lafayette RA, Rovin BH, Aslam N, Hladunewich MA, Irazabal MV, Sethi S, Gipson DS, Reich HN, Brenchley P, Kretzler M, Radhakrishnan J, Hebert LA, Gipson PE, Thomas LF, McCarthy ET, Appel GB, Jefferson JA, Eirin A, Lieske JC, Hogan MC, Greene EL, Dillon JJ, Leung N, Sedor JR, Rizk DV, Blumenthal SS, Lasic LB, Juncos LA, Green DF, Simon J, Sussman AN, Philibert D, Cattran DC, Mentor Consortium group.
- Issue date: 2015
- Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy.
- Authors: Ruggenenti P, Debiec H, Ruggiero B, Chianca A, Pellé T, Gaspari F, Suardi F, Gagliardini E, Orisio S, Benigni A, Ronco P, Remuzzi G
- Issue date: 2015 Oct
- Efficacy and safety of rituximab in the treatment of membranous nephropathy: A systematic review and meta-analysis.
- Authors: Lu W, Gong S, Li J, Luo H, Wang Y
- Issue date: 2020 Apr
- Rituximab for the treatment of membranous nephropathy: a single-center experience.
- Authors: Aleš Rigler A, Jerman A, Orsag A, Kojc N, Kovač D, Škoberne A, Borštnar Š, Večerić Haler Ž, Avguštin N, Kveder R, Ferluga D, Vizjak A, Lindič J
- Issue date: 2017 Supplement 1
- The Effect of Mycophenolate Mofetil versus Cyclosporine as Combination Therapy with Low Dose Corticosteroids in High-risk Patients with Idiopathic Membranous Nephropathy: a Multicenter Randomized Trial.
- Authors: Choi JY, Kim DK, Kim YW, Yoo TH, Lee JP, Chung HC, Cho KH, An WS, Lee DH, Jung HY, Cho JH, Kim CD, Kim YL, Park SH
- Issue date: 2018 Feb 26