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

被引：51

作者：

Fervenza, Fernando C. ^{[1
]}

Canetta, Pietro A. ^{[2
]}

Barbour, Sean J. ^{[3
]}

Lafayette, Richard A. ^{[4
]}

Rovin, Brad H. ^{[5
]}

Aslam, Nabeel ^{[6
]}

Hladunewich, Michelle A. ^{[7
]}

Irazabal, Maria V. ^{[1
]}

Sethi, Sanjeev ^{[8
]}

Gipson, Debbie S. ^{[9
]}

Reich, Heather N. ^{[7
]}

Brenchley, Paul ^{[10
]}

Kretzler, Matthias ^{[11
]}

Radhakrishnan, Jai ^{[2
]}

Hebert, Lee A. ^{[5
]}

Gipson, Patrick E. ^{[9
]}

Thomas, Leslie F. ^{[12
]}

McCarthy, Ellen T. ^{[13
]}

Appel, Gerald B. ^{[2
]}

Jefferson, J. Ashley ^{[14
]}

Eirin, Alfonso ^{[1
]}

Lieske, John C. ^{[1
]}

Hogan, Marie C. ^{[1
]}

Greene, Eddie L. ^{[1
]}

Dillon, John J. ^{[1
]}

Leung, Nelson ^{[1
]}

Sedor, John R. ^{[15
]}

Rizk, Dana V. ^{[16
]}

Blumenthal, Samuel S. ^{[17
]}

Lasic, Lada B. ^{[18
]}

Juncos, Luis A. ^{[19
]}

Green, Dollie F. ^{[20
]}

Simon, James ^{[21
]}

Sussman, Amy N. ^{[22
]}

Philibert, David ^{[23
]}

Cattran, Daniel C. ^{[7
]}

机构：

[1] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA

[2] Columbia Univ, Div Nephrol, New York, NY USA

[3] Univ British Columbia, Div Nephrol, Vancouver, BC V5Z 1M9, Canada

[4] Stanford Univ, Med Ctr, Div Nephrol & Hypertens, Sanford, CA USA

[5] Ohio State Univ, Div Nephrol, Columbus, OH 43210 USA

[6] Mayo Clin, Div Nephrol & Hypertens, Jacksonville, FL 32224 USA

[7] Toronto Gen Hosp, Univ Hlth Network, Toronto, ON M5G 2M9, Canada

[8] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA

[9] Univ Michigan, Div Nephrol, Ann Arbor, MI USA

[10] Manchester Royal Infirm, Manchester M13 9WL, Lancs, England

[11] Univ Michigan, Internal Med Nephrol & Computat Med & Bioinformat, Ann Arbor, MI 48109 USA

[12] Mayo Clin, Div Nephrol & Hypertens, Scottsdale, AZ USA

[13] Univ Kansas, Med Ctr, Div Nephrol & Hypertens, Kansas City, KS 66103 USA

[14] Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA

[15] Case Western Reserve Univ, Dept Med & Physiol Biophys, Cleveland, OH 44106 USA

[16] Univ Alabama Birmingham, Div Nephrol, Birmingham, AL USA

[17] Med Coll Wisconsin, Div Nephrol, Milwaukee, WI 53226 USA

[18] NYU, Div Nephrol, New York, NY USA

[19] Univ Mississippi, Med Ctr, Div Nephrol, Jackson, MS 39216 USA

[20] Univ Miami, Div Nephrol & Hypertens, Miami, FL USA

[21] Cleveland Clin, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA

[22] Univ Arizona, Div Nephrol, Tucson, AZ USA

[23] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada

来源：

NEPHRON | 2015年 / 130卷 / 03期

关键词：

Idiopathic membranous nephropathy; Rituximab; Cyclosporine; Glomerular disease; Proteinuria; NEPHROTIC SYNDROME; IMMUNOSUPPRESSIVE THERAPY; CYCLOPHOSPHAMIDE THERAPY; RECEPTOR; ANTIBODIES; DISEASE; AUTOANTIBODIES; GLOMERULOPATHY; MALIGNANCIES; PROTEINURIA;

D O I：

10.1159/000430849

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

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 IV 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. (C) 2015 S. Karger AG, Basel

引用

页码：159 / 168

页数：10

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