Rituximab is an effective treatment for lupus nephritis and allows a reduction in maintenance steroids

被引:126
作者
Pepper, Ruth [1 ,2 ]
Griffith, Megan [1 ,2 ]
Kirwan, Chris [1 ,2 ]
Levy, Jeremy [1 ,2 ]
Taube, David [1 ,2 ]
Pusey, Charles [3 ]
Lightstone, Liz [1 ,2 ,3 ]
Cairns, Tom [1 ,2 ]
机构
[1] Hammersmith Hosp, Imperial Coll Kidney, W London Renal & Transplant Ctr, London, England
[2] Hammersmith Hosp, Transplant Inst, W London Renal & Transplant Ctr, London, England
[3] Univ London Imperial Coll Sci Technol & Med, Div Med, Renal Sect, London, England
关键词
immunosuppression; lupus nephritis; mycophenolate mofetil; rituximab; steroids; B-CELL DEPLETION; MYCOPHENOLATE-MOFETIL; RISK-FACTORS; THERAPY; ERYTHEMATOSUS; REMISSION; DETERMINANTS; METAANALYSIS; ASSOCIATION; INDUCTION;
D O I
10.1093/ndt/gfp336
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
Background. Lupus nephritis is a life-threatening complication of SLE. Treatment regimes include steroids and cyclophosphamide, both associated with significant morbidity. Newer regimes include mycophenolate mofetil (MMF). We report our outcomes in a prospectively monitored cohort of patients receiving our new standard treatment protocol, comprising rituximab induction therapy and MMF maintenance in patients already taking maintenance immunosuppression for SLE who developed lupus nephritis. We then attempted steroid reduction/withdrawal. Methods. Patients with class III/IV/V lupus nephritis were included. All patients were on steroids prior to the development of lupus nephritis. Eighteen patients have reached at least 1 year follow-up. These patients received rituximab induction therapy and MMF maintenance therapy. Steroid reduction/withdrawal was guided by clinical response. Results. Fourteen of 18 (78%) patients achieved complete or partial remission with a sustained response of 12/18 (67%) at 1 year, with 2 patients having a relapse of proteinuria. Four patients did not respond. There was a significant decrease in proteinuria from a mean protein: creatinine ratio (PCR) of 325 mg/mmol at presentation to 132 mg/mmol at 1 year (P = 0.004). Serum albumin significantly increased from a mean of 29 g/L at presentation to 34 g/L at 1 year (P = 0.001). The complication rate was low with no severe infections. Following treatment with rituximab, 6 patients stopped prednisolone, 6 patients reduced their maintenance dose and 6 patients remained on the same dose (maximum 10 mg). Conclusion. This data demonstrates the efficacy of a rituximab and MMF based regime in the treatment of lupus nephritis, allowing a reduction or total withdrawal of corticosteroids.
引用
收藏
页码:3717 / 3723
页数:8
相关论文
共 34 条
[1]   Variability in the biological response to anti-CD20 B cell depletion in systemic lupus erythaematosus [J].
Albert, D. ;
Dunham, J. ;
Khan, S. ;
Stansberry, J. ;
Kolasinski, S. ;
Tsai, D. ;
Pullman-Mooar, S. ;
Barnack, F. ;
Striebich, C. ;
Looney, R. J. ;
Prak, E. T. Luning ;
Kimberly, R. ;
Zhang, Y. ;
Eisenberg, R. .
ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (12) :1724-1731
[2]   Delayed memory B cell recovery in peripheral blood and lymphoid tissue in systemic lupus erythematosus after B cell depletion therapy [J].
Anolik, Jennifer H. ;
Barnard, Jennifer ;
Owen, Teresa ;
Zheng, Bo ;
Kemshetti, Sunil ;
Looney, R. John ;
Sanz, Inaki .
ARTHRITIS AND RHEUMATISM, 2007, 56 (09) :3044-3056
[3]   The relationship of FcγRIIIa genotype to degree of B cell depletion by rituximab in the treatment of systemic lupus erythematosus [J].
Anolik, JH ;
Campbell, D ;
Felgar, RE ;
Young, F ;
Sanz, I ;
Rosenblatt, J ;
Looney, RJ .
ARTHRITIS AND RHEUMATISM, 2003, 48 (02) :455-459
[4]   Clinical evaluation and monitoring of lupus kidney disease [J].
Austin, HA .
LUPUS, 1998, 7 (09) :618-621
[5]   Mycophenolic acid 12-h trough level monitoring in renal transplantation: Association with acute rejection and toxicity [J].
Borrows, R ;
Chusney, G ;
Loucaidou, M ;
James, A ;
Lee, J ;
Tromp, JV ;
Owen, J ;
Cairns, T ;
Griffith, M ;
Hakim, N ;
McLean, A ;
Palmer, A ;
Papalois, V ;
Taube, D .
AMERICAN JOURNAL OF TRANSPLANTATION, 2006, 6 (01) :121-128
[6]   Determinants of mycophenolic acid levels after renal transplantation [J].
Borrows, R ;
Chusney, G ;
James, A ;
Stichbury, J ;
Van Tromp, J ;
Cairns, T ;
Griffith, M ;
Hakim, N ;
McLean, A ;
Palmer, A ;
Papalois, V ;
Taube, D .
THERAPEUTIC DRUG MONITORING, 2005, 27 (04) :442-450
[7]   SYSTEMIC LUPUS-ERYTHEMATOSUS - EMERGING CONCEPTS .1. RENAL, NEUROPSYCHIATRIC, CARDIOVASCULAR, PULMONARY, AND HEMATOLOGIC DISEASE [J].
BOUMPAS, DT ;
AUSTIN, HA ;
FESSLER, BJ ;
BALOW, JE ;
KLIPPEL, JH ;
LOCKSHIN, MD .
ANNALS OF INTERNAL MEDICINE, 1995, 122 (12) :940-950
[8]   B cell depletion therapy in systemic lupus erythaematosus: relationships among serum B lymphocyte stimulator levels, autoantibody profile and clinical response [J].
Cambridge, G. ;
Isenberg, D. A. ;
Edwards, J. C. W. ;
Leandro, M. J. ;
Migone, T-S ;
Teodorescu, M. ;
Stohl, W. .
ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (07) :1011-1016
[9]   Complete remission of lupus nephritis with rituximab and steroids for induction and rituximab alone for maintenance therapy [J].
Camous, Laurent ;
Melander, Catherine ;
Vallet, Marion ;
Squalli, Tarek ;
Knebelmann, Bertrand ;
Noel, Laure-Helene ;
Fakhouri, Fadi .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2008, 52 (02) :346-352
[10]   Sequential therapies for proliferative lupus nephritis [J].
Contreras, G ;
Pardo, V ;
Leclercq, B ;
Lenz, O ;
Tozman, E ;
O'Nan, P ;
Roth, D .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 350 (10) :971-980