Treatment of Lupus Nephritis With Abatacept

被引:209
作者
Askanase, Anca D. [1 ]
Byron, Margie [2 ]
Keyes-Elstein, Lynette L. [2 ]
Cagnoli, Patricia C. [3 ]
McCune, W. Joseph [3 ]
Chatham, W. Winn [4 ]
Contreras, Gabriel [5 ]
Daikh, David I.
Dall'Era, Maria [6 ,7 ]
Wofsy, David [6 ,7 ]
Davidson, Anne [8 ]
Diamond, Betty [8 ]
Mackay, Meggan [8 ]
Ding, Linna [9 ]
Gao, Wendy [9 ]
Dooley, Mary Anne [10 ,11 ]
Fragoso-Loyo, Hilda [12 ]
Sanchez-Guerrero, Jorge [12 ]
Karp, David R. [13 ]
Olsen, Nancy J. [13 ]
Jolly, Meenakshi [14 ]
Kalunian, Kenneth [15 ]
Kamen, Diane [16 ]
Lee, Iris [17 ]
Levesque, Marc C. [18 ]
Lim, S. Sam [19 ]
Ramos-Remus, Cesar [20 ]
Rovin, Brad H. [21 ]
Sayre, Peter H. [22 ]
Smilek, Dawn E. [22 ]
Tosta, Patti [22 ]
Utset, Tammy O. [23 ]
Venuturupalli, Swamy [24 ,25 ]
Winchester, Robert [26 ]
机构
[1] NYU, New York, NY USA
[2] Rho Inc, Chapel Hill, NC USA
[3] Univ Michigan, Ann Arbor, MI 48109 USA
[4] Univ Alabama Birmingham, Birmingham, AL USA
[5] Univ Miami, Coral Gables, FL 33124 USA
[6] Univ Calif San Francisco, Div Rheumatol, San Francisco, CA 94143 USA
[7] Russell Engleman Rheumatol Res Ctr, San Francisco, CA USA
[8] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA
[9] NIAID, NIH, Bethesda, MD 20892 USA
[10] Univ N Carolina, Chapel Hill, NC USA
[11] Thurston Arthrit Res Ctr, Chapel Hill, NC USA
[12] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Mexico City, DF, Mexico
[13] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA
[14] Rush Univ, Med Ctr, Chicago, IL 60612 USA
[15] Univ Calif San Diego, La Jolla, CA 92093 USA
[16] Med Univ S Carolina, Charleston, SC USA
[17] Temple Univ, Philadelphia, PA 19122 USA
[18] Univ Pittsburgh, Pittsburgh, PA USA
[19] Emory Univ, Atlanta, GA 30322 USA
[20] Unidad Invest Enfermedades Cronico Degenerativas, Guadalajara, Jalisco, Mexico
[21] Ohio State Univ, Columbus, OH 43210 USA
[22] NIAID, Immune Tolerance Network, San Francisco, CA USA
[23] Univ Chicago, Chicago, IL 60637 USA
[24] Univ Calif Los Angeles, Los Angeles, CA USA
[25] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
[26] Columbia Univ, New York, NY USA
关键词
MYCOPHENOLATE-MOFETIL; INTRAVENOUS CYCLOPHOSPHAMIDE; RHEUMATOID-ARTHRITIS; ERYTHEMATOSUS SLE; RANDOMIZED-TRIAL; MURINE LUPUS; THERAPY; GLOMERULONEPHRITIS; CLASSIFICATION; COSTIMULATION;
D O I
10.1002/art.38790
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To assess the efficacy and safety of a 24-week course of abatacept in the treatment of active lupus nephritis and to assess the potential of abatacept to induce "clinical tolerance," defined as sustained clinical quiescence of lupus nephritis after discontinuation of immunosuppressive therapy. Methods. Patients with active lupus nephritis (n = 134) were enrolled in a randomized, double-blind phase II add-on trial in which they received either abatacept or placebo in conjunction with the Euro-Lupus Nephritis Trial regimen of low-dose cyclophosphamide (CYC) followed by azathioprine (AZA). The primary efficacy outcome was the frequency of complete response at week 24. Thereafter, patients who met either complete or partial response criteria continued blinded treatment through week 52. During this phase of the study, subjects in the abatacept treatment group in whom a complete response was achieved at week 24 discontinued immunosuppressive therapy other than prednisone (10 mg/day). Results. There were no statistically significant differences between groups with respect to the primary outcome or any of the secondary outcomes, including measures of safety. A complete response was achieved in 33% of the subjects in the treatment group and in 31% of the subjects in the control group at week 24. Fifty percent of the subjects in the treatment group who met complete response criteria and therefore discontinued immunosuppressive therapy at week 24 maintained their complete response status through week 52. Conclusion. The addition of abatacept to a regimen of CYC followed by AZA did not improve the outcome of lupus nephritis at either 24 or 52 weeks. No worrisome safety signals were encountered.
引用
收藏
页码:3096 / 3104
页数:9
相关论文
共 34 条
[1]   Mycophenolate Mofetil versus Cyclophosphamide for Induction Treatment of Lupus Nephritis [J].
Appel, Gerald B. ;
Contreras, Gabriel ;
Dooley, Mary Anne ;
Ginzler, Ellen M. ;
Isenberg, David ;
Jayne, David ;
Li, Lei-Shi ;
Mysler, Eduardo ;
Sanchez-Guerrero, Jorge ;
Solomons, Neil ;
Wofsy, David .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2009, 20 (05) :1103-1112
[2]   THERAPY OF LUPUS NEPHRITIS - CONTROLLED TRIAL OF PREDNISONE AND CYTOTOXIC DRUGS [J].
AUSTIN, HA ;
KLIPPEL, JH ;
BALOW, JE ;
LERICHE, NGH ;
STEINBERG, AD ;
PLOTZ, PH ;
DECKER, JL .
NEW ENGLAND JOURNAL OF MEDICINE, 1986, 314 (10) :614-619
[3]   CD28-mediated regulation of multiple myeloma cell proliferation and survival [J].
Bahlis, Nizar J. ;
King, Anne M. ;
Kolonias, Despina ;
Carlson, Louise M. ;
Liu, Hong Yu ;
Hussein, Mohamad A. ;
Terebelo, Howard R. ;
Byrne, Gerald E., Jr. ;
Levine, Bruce L. ;
Boise, Lawrence H. ;
Lee, Kelvin P. .
BLOOD, 2007, 109 (11) :5002-5010
[4]   Efficacy of mycophenolate mofetil in patients with diffuse proliferative lupus nephritis [J].
Chan, TM ;
Li, FK ;
Tang, CSO ;
Wong, RWS ;
Fang, GX ;
Ji, YL ;
Lau, CS ;
Wong, AKM ;
Tong, MKL ;
Chan, KW ;
Lai, KN .
NEW ENGLAND JOURNAL OF MEDICINE, 2000, 343 (16) :1156-1162
[5]   The role of cytokines, CTLA-4 and costimulation in transplant tolerance and rejection [J].
Dai, ZH ;
Lakkis, FG .
CURRENT OPINION IN IMMUNOLOGY, 1999, 11 (05) :504-508
[6]   Cutting edge: Reversal of murine lupus nephritis with CTLA4Ig and cyclophosphamide [J].
Daikh, DI ;
Wofsy, D .
JOURNAL OF IMMUNOLOGY, 2001, 166 (05) :2913-2916
[7]   Mycophenolate versus Azathioprine as Maintenance Therapy for Lupus Nephritis [J].
Dooley, Mary Anne ;
Jayne, David ;
Ginzler, Ellen M. ;
Isenberg, David ;
Olsen, Nancy J. ;
Wofsy, David ;
Eitner, Frank ;
Appel, Gerald B. ;
Contreras, Gabriel ;
Lisk, Laura ;
Solomons, Neil .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (20) :1886-1895
[8]   Epidemiology and sociodemographics of systemic lupus erythematosus and lupus nephritis among US adults with Medicaid coverage, 20002004 [J].
Feldman, Candace H. ;
Hiraki, Linda T. ;
Liu, Jun ;
Fischer, Michael A. ;
Solomon, Daniel H. ;
Alarcon, Graciela S. ;
Winkelmayer, Wolfgang C. ;
Costenbader, Karen H. .
ARTHRITIS AND RHEUMATISM, 2013, 65 (03) :753-763
[9]   A multiethnic, multicenter cohort of patients with systemic lupus erythematosus (SLE) as a model for the study of ethnic disparities in SLE [J].
Fernandez, Monica ;
Alarcon, Graciela S. ;
Calvo-Alen, Jaime ;
Andrade, Rosa ;
McGwin, Gerald, Jr. ;
Vila, Luis M. ;
Reveille, John D. .
ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH, 2007, 57 (04) :576-584
[10]   TREATMENT OF MURINE LUPUS WITH CTLA4IG [J].
FINCK, BK ;
LINSLEY, PS ;
WOFSY, D .
SCIENCE, 1994, 265 (5176) :1225-1227