Disease Control and Safety of Belimumab Plus Standard Therapy Over 7 Years in Patients with Systemic Lupus Erythematosus

被引:141
作者
Ginzler, Ellen M.
Wallace, Daniel J.
Merrill, Joan T.
Furie, Richard A.
Stohl, William
Chatham, W. Winn
Weinstein, Arthur
McKay, James D.
McCune, W. Joseph
Zhong, Z. John
Freimuth, William W.
Petri, Michelle A.
机构
[1] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90024 USA
[3] Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA
[4] North Shore Long Isl Jewish Hlth Syst, Lake Success, NY USA
[5] Los Angeles Cty Univ Southern Calif, Med Ctr, Los Angeles, CA USA
[6] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA
[7] Univ Alabama Birmingham, Birmingham, AL USA
[8] MedStar Washington Hosp Ctr, Washington, DC USA
[9] Oklahoma Ctr Arthrit Therapy & Res, Tulsa, OK USA
[10] Univ Michigan, Ann Arbor, MI 48109 USA
[11] Human Genome Sci Inc, Rockville, MD USA
[12] Johns Hopkins Univ, Sch Med, Baltimore, MD USA
关键词
BELIMUMAB; SELENA-SLEDAI SLE RESPONDER INDEX; SYSTEMIC LUPUS ERYTHEMATOSUS; B-LYMPHOCYTE STIMULATOR; ORGAN DAMAGE; MONOCLONAL-ANTIBODY; SJOGRENS-SYNDROME; DOUBLE-BLIND; BILAG INDEX; MORTALITY; COHORT; ASSOCIATION; FLARES;
D O I
10.3899/jrheum.121368
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To evaluate the efficacy/safety of belimumab plus standard therapy in patients (n = 449) with active systemic lupus erythematosus (SLE) treated up to 7 years (n = 177 currently ongoing). Methods. Patients (n = 345) who completed a double-blind, placebo-controlled, 52-week study of belimumab 1, 4, or 10 mg/kg and 24-week extension of belimumab (placebo switched to 10 mg/kg; belimumab same dose or switched to 10 mg/kg) could receive belimumab 10 mg/kg in an open-label continuation study (n = 296). Disease activity was analyzed in patients with active SLE at baseline of the initial study. Biomarker and SLE medication changes were evaluated, and adverse events (AE) were monitored throughout the study. Results. Total belimumab exposure over 7 years (double-blind and open-label periods): 1746 patient-years. SLE Responder Index (SRI) response rates at Week 52 in autoantibody-positive patients: placebo, 29%; belimumab, 46% (p < 0.05). In the continuation study, 57% of autoantibody- positive patients had an SRI response by Year 2 and 65% by Year 7; severe flares occurred in 19% with placebo and 17% with belimumab during the first year, with the annual rate declining to 2%-9% during years 2-7. Anti-dsDNA autoantibodies in patients positive for them at baseline had a progressive decline of 40%-60% from baseline over 2-7 years with belimumab. Corticosteroid use decreased over time with ≥ 50-55% reduction in median dose during years 5-7. Serious and overall annual AE rates, including infections, were generally stable or decreased during 7-year treatment. Conclusion. Disease control and safety profile were maintained in patients with active SLE taking belimumab plus standard therapy for up to 7 years. [ClinicalTrials.gov numbers: NCT00071487 and NCT00583362] (First Release Nov 1 2013; J Rheumatol 2014;41:300.7; doi:10.3899/jrheum.121368). © The Journal of Rheumatology Copyright 2014. All rights reserved.
引用
收藏
页码:300 / 309
页数:10
相关论文
共 42 条
[1]   Generation and characterization of LymphoStat-B, a human monoclonal antibody that antagonizes the bioactivities of B lymphocyte stimulator [J].
Baker, KP ;
Edwards, BM ;
Main, SH ;
Choi, GH ;
Wager, RE ;
Halpern, WG ;
Lappin, PB ;
Riccobene, T ;
Abramian, D ;
Sekut, L ;
Sturm, B ;
Poortman, C ;
Minter, RR ;
Dobson, CL ;
Williams, E ;
Carmen, S ;
Smith, R ;
Roschke, V ;
Hilbert, DM ;
Vaughan, TJ ;
Albert, VR .
ARTHRITIS AND RHEUMATISM, 2003, 48 (11) :3253-3265
[2]   The relationship between cancer and medication exposures in systemic lupus erythaematosus:: a case-cohort study [J].
Bernatsky, S. ;
Joseph, L. ;
Boivin, J-F ;
Gordon, C. ;
Urowitz, M. ;
Gladman, D. ;
Fortin, P. R. ;
Ginzler, E. ;
Bae, S-C ;
Barr, S. ;
Edworthy, S. ;
Isenberg, D. ;
Rahman, A. ;
Petri, M. ;
Alarcon, G. S. ;
Aranow, C. ;
Dooley, M-A ;
Rajan, R. ;
Senecal, J-L ;
Zummer, M. ;
Manzi, S. ;
Ramsey-Goldman, R. ;
Clarke, A. E. .
ANNALS OF THE RHEUMATIC DISEASES, 2008, 67 (01) :74-79
[3]   Mortality in systemic lupus erythematosus [J].
Bernatsky, S. ;
Boivin, J. -F. ;
Joseph, L. ;
Manzi, S. ;
Ginzler, E. ;
Gladman, D. D. ;
Urowitz, M. ;
Fortin, P. R. ;
Petri, M. ;
Barr, S. ;
Gordon, C. ;
Bae, S. -C. ;
Isenberg, D. ;
Zoma, A. ;
Aranow, C. ;
Dooley, M. -A. ;
Nived, O. ;
Sturfelt, G. ;
Steinsson, K. ;
Alarcon, G. ;
Senecal, J. -L. ;
Zummer, M. ;
Hanly, J. ;
Ensworth, S. ;
Pope, J. ;
Edworthy, S. ;
Rahman, A. ;
Sibley, J. ;
El-Gabalawy, H. ;
McCarthy, T. ;
Pierre, Y. St. ;
Clarke, A. ;
Ramsey-Goldman, R. .
ARTHRITIS AND RHEUMATISM, 2006, 54 (08) :2550-2557
[4]   An International Cohort Study of Cancer in Systemic Lupus Erythematosus [J].
Bernatsky, S ;
Boivin, JF ;
Joseph, L ;
Rajan, R ;
Zoma, A ;
Manzi, S ;
Ginzler, E ;
Urowitz, M ;
Gladman, D ;
Fortin, PR ;
Petri, M ;
Edworthy, S ;
Barr, S ;
Gordon, C ;
Bae, SC ;
Sibley, J ;
Isenberg, D ;
Rahman, A ;
Aranow, C ;
Dooley, MA ;
Steinsson, K ;
Nived, O ;
Sturfelt, G ;
Alarcón, G ;
Senécal, JL ;
Zummer, M ;
Hanly, J ;
Ensworth, S ;
Pope, J ;
El-Gabalawy, H ;
McCarthy, T ;
Pierre, YS ;
Ramsey-Goldman, R ;
Clarke, A .
ARTHRITIS AND RHEUMATISM, 2005, 52 (05) :1481-1490
[5]   The effect of combined estrogen and progesterone hormone replacement therapy on disease activity in systemic lupus erythematosus:: A randomized trial [J].
Buyon, JP ;
Petri, MA ;
Kim, MY ;
Kalunian, KC ;
Grossman, J ;
Hahn, BH ;
Merrill, JT ;
Sammaritano, L ;
Lockshin, M ;
Alarcón, GS ;
Manzi, S ;
Belmont, HM ;
Askanase, AD ;
Sigler, L ;
Dooley, MA ;
Von Feldt, J ;
McCune, WJ ;
Friedman, A ;
Wachs, J ;
Cronin, M ;
Hearth-Holmes, M ;
Tan, M ;
Licciardi, F .
ANNALS OF INTERNAL MEDICINE, 2005, 142 (12) :953-962
[6]   Morbidity and mortality in systemic lupus erythematosus during a 10-year period -: A comparison of early and late manifestations in a cohort of 1,000 patients [J].
Cervera, R ;
Khamashta, MA ;
Font, J ;
Sebastiani, GD ;
Gil, A ;
Lavilla, P ;
Mejía, JC ;
Aydintug, AC ;
Chwalinska-Sadowska, H ;
de Ramón, E ;
Fernández-Nebro, A ;
Galeazzi, M ;
Valen, M ;
Mathieu, A ;
Houssiau, FD ;
Caro, N ;
Alba, P ;
Ramos-Casals, M ;
Ingelmo, M ;
Hughes, GRV .
MEDICINE, 2003, 82 (05) :299-308
[7]  
Cheema GS, 2001, ARTHRITIS RHEUM-US, V44, P1313, DOI 10.1002/1529-0131(200106)44:6<1313::AID-ART223>3.0.CO
[8]  
2-S
[9]   A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus [J].
Furie, Richard ;
Petri, Michelle ;
Zamani, Omid ;
Cervera, Ricard ;
Wallace, Daniel J. ;
Tegzova, Dana ;
Sanchez-Guerrero, Jorge ;
Schwarting, Andreas ;
Merrill, Joan T. ;
Chatham, W. Winn ;
Stohl, William ;
Ginzler, Ellen M. ;
Hough, Douglas R. ;
Zhong, Z. John ;
Freimuth, William ;
van Vollenhoven, Ronald F. .
ARTHRITIS AND RHEUMATISM, 2011, 63 (12) :3918-3930
[10]   Novel Evidence-Based Systemic Lupus Erythematosus Responder Index [J].
Furie, Richard A. ;
Petri, Michelle A. ;
Wallace, Daniel J. ;
Ginzler, Ellen M. ;
Merrill, Joan T. ;
Stohl, William ;
Chatham, W. Winn ;
Strand, Vibeke ;
Weinstein, Arthur ;
Chevrier, Marc R. ;
Zhong, Z. John ;
Freimuth, William W. .
ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH, 2009, 61 (09) :1143-1151