A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR)

Mentor Consortium group, John J. Dillon

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

BACKGROUND: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria.

METHODS AND DESIGN: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study.

DISCUSSION: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

Original languageEnglish (US)
Pages (from-to)159-168
Number of pages10
JournalNephron
Volume130
Issue number3
DOIs
StatePublished - 2015

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Membranous Glomerulonephritis
Proteinuria
Cyclosporine
Randomized Controlled Trials
Therapeutics
Random Allocation
B-Lymphocytes
Rituximab
Nephrotic Syndrome
Patient Safety
Immunosuppressive Agents
Treatment Failure
Angiotensin II
Monoclonal Antibodies
Recurrence

ASJC Scopus subject areas

  • Nephrology

Cite this

A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR). / Mentor Consortium group; Dillon, John J.

In: Nephron, Vol. 130, No. 3, 2015, p. 159-168.

Research output: Contribution to journalArticle

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title = "A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR)",
abstract = "BACKGROUND: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria.METHODS AND DESIGN: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25{\%}) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25{\%}) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25{\%} (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study.DISCUSSION: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.",
author = "{Mentor Consortium group} and Fervenza, {Fernando Custodio} and Canetta, {Pietro A.} and Barbour, {Sean J.} and Lafayette, {Richard A.} and Rovin, {Brad H.} and Nabeel Aslam and Hladunewich, {Michelle A.} and {Irazabal Mira}, Maria and Sethi, {Sanjeev M} and Gipson, {Debbie S.} and Reich, {Heather N.} and Paul Brenchley and Matthias Kretzler and Jai Radhakrishnan and Hebert, {Lee A.} and Gipson, {Patrick E.} and Thomas, {Leslie Francis} and McCarthy, {Ellen T.} and Appel, {Gerald B.} and Jefferson, {J. Ashley} and Alfonso Eirin and Lieske, {John C} and Hogan, {Marie C} and Dillon, {John J.} and Dillon, {John J.} and Nelson Leung and Sedor, {John R.} and Rizk, {Dana V.} and Blumenthal, {Samuel S.} and Lasic, {Lada B.} and Juncos, {Luis A.} and Green, {Dollie F.} and James Simon and Sussman, {Amy N.} and David Philibert and Cattran, {Daniel C.}",
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T1 - A Multicenter Randomized Controlled Trial of Rituximab versus Cyclosporine in the Treatment of Idiopathic Membranous Nephropathy (MENTOR)

AU - Mentor Consortium group

AU - Fervenza, Fernando Custodio

AU - Canetta, Pietro A.

AU - Barbour, Sean J.

AU - Lafayette, Richard A.

AU - Rovin, Brad H.

AU - Aslam, Nabeel

AU - Hladunewich, Michelle A.

AU - Irazabal Mira, Maria

AU - Sethi, Sanjeev M

AU - Gipson, Debbie S.

AU - Reich, Heather N.

AU - Brenchley, Paul

AU - Kretzler, Matthias

AU - Radhakrishnan, Jai

AU - Hebert, Lee A.

AU - Gipson, Patrick E.

AU - Thomas, Leslie Francis

AU - McCarthy, Ellen T.

AU - Appel, Gerald B.

AU - Jefferson, J. Ashley

AU - Eirin, Alfonso

AU - Lieske, John C

AU - Hogan, Marie C

AU - Dillon, John J.

AU - Dillon, John J.

AU - Leung, Nelson

AU - Sedor, John R.

AU - Rizk, Dana V.

AU - Blumenthal, Samuel S.

AU - Lasic, Lada B.

AU - Juncos, Luis A.

AU - Green, Dollie F.

AU - Simon, James

AU - Sussman, Amy N.

AU - Philibert, David

AU - Cattran, Daniel C.

PY - 2015

Y1 - 2015

N2 - BACKGROUND: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria.METHODS AND DESIGN: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study.DISCUSSION: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

AB - BACKGROUND: Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria.METHODS AND DESIGN: Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study.DISCUSSION: This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic membranous nephropathy.

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