Treatment of systemic lupus erythematosus by inhibition of T cell costimulation with anti-CD154 - A randomized, double-blind, placebo-controlled trial

被引:257
作者
Kalunian, KC
Davis, JC
Merrill, JT
Totoritis, MQ
Wofsy, D
机构
[1] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA
[2] Univ Calif San Francisco, Sch Med, San Francisco, CA USA
[3] St Lukes Roosevelt Hosp, New York, NY USA
[4] Idec Pharmaceut Corp, San Diego, CA USA
来源
ARTHRITIS AND RHEUMATISM | 2002年 / 46卷 / 12期
关键词
D O I
10.1002/art.10681
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To evaluate the safety and efficacy of a humanized monoclonal antibody against CD154 (IDEC-131) in patients with active systemic lupus erythematosus (SLE). Methods. In this phase II, double-blind, placebo-controlled, multiple-center, multiple-dose study, 85 patients with mild-to-moderately active SLE were randomized to receive 6 infusions of IDEC-131, ranging from 2.5 mg/kg to 10.0 mg/kg, or placebo over 16 weeks. Efficacy was assessed at week 20, primarily by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and secondarily, by multiple measures of disease activity. Safety was assessed through week 28 by clinical and laboratory evaluation. Immunogenicity studies were also performed. Results. SLEDAI scores improved from the baseline levels of disease activity in all groups, including the placebo group. However, these scores were not statistically different among the IDEC-131 treatment and placebo groups at week 20. Evaluations of secondary variables did not indicate significant differences between the IDEC-131 treatment and placebo groups. The type and frequency of adverse events were similar between the IDEC-131 and placebo groups. Conclusion. IDEC-131 administered at doses ranging 2.5-10.0 mg/kg over 16 weeks was safe and well tolerated in patients with SLE. Efficacy of the drug compared with placebo was not demonstrated. There were statistically significant improvements from baseline in all groups, including the placebo group.
引用
收藏
页码:3251 / 3258
页数:8
相关论文
共 25 条
[1]  
Anderson D, 2000, ARTHRITIS RHEUM, V43, pS51
[2]  
BUHLMANN JE, 1995, IMMUNITY, V2, P645
[3]  
Daikh DI, 1997, J IMMUNOL, V159, P3104
[4]  
Davis JC, 2001, J RHEUMATOL, V28, P95
[5]   Hyperexpression of CD40 ligand by B and T cells in human lupus and its role in pathogenic autoantibody production [J].
DesaiMehta, A ;
Lu, LJ ;
RamseyGoldman, R ;
Datta, SK .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 97 (09) :2063-2073
[6]   THE ROLE OF CD40 IN THE REGULATION OF HUMORAL AND CELL-MEDIATED-IMMUNITY [J].
DURIE, FH ;
FOY, TM ;
MASTERS, SR ;
LAMAN, JD ;
NOELLE, RJ .
IMMUNOLOGY TODAY, 1994, 15 (09) :406-411
[7]   Immune regulation by CD40 and its ligand GP39 [J].
Foy, TM ;
Aruffo, A ;
Bajorath, J ;
Buhlmann, JE ;
Noelle, RJ .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :591-617
[8]   CD40 and CD154 in cell-mediated immunity [J].
Grewal, IS ;
Flavell, RA .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :111-135
[9]   Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus [J].
Hochberg, MC .
ARTHRITIS AND RHEUMATISM, 1997, 40 (09) :1725-1725
[10]   SIGNALS AND SIGNS FOR LYMPHOCYTE-RESPONSES [J].
JANEWAY, CA ;
BOTTOMLY, K .
CELL, 1994, 76 (02) :275-285