Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial

被引:71
作者
Mitha, Essack [1 ]
Schumacher, H. Ralph [2 ,3 ]
Fouche, Leon [4 ]
Luo, Shue-Fen [5 ,6 ]
Weinstein, Steven P. [7 ]
Yancopoulos, George D. [7 ]
Wang, Jian [7 ]
King-Davis, Shirletta [7 ]
Evans, Robert R. [7 ]
机构
[1] Newtown Clin Res, Johannesburg, South Africa
[2] VA Med Ctr, Philadelphia, PA USA
[3] Univ Penn, Philadelphia, PA 19104 USA
[4] Limpopo Clin Res Initiat, Thabazimbi, South Africa
[5] Chang Gung Mem Hosp Lin Kou, Div Rheumatol Allergy & Immunol, Tao Yuan, Taiwan
[6] Chang Gung Univ, Tao Yuan, Taiwan
[7] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA
关键词
crystal arthropathies; clinical trials and methods; cytokines and inflammatory mediators; inflammation; biologic therapies; IL-1; INHIBITION; SERUM URATE; ALLOPURINOL; ANAKINRA; INFLAMMATION; ADHERENCE; ARTHRITIS; CARE; HYPERURICEMIA; FEBUXOSTAT;
D O I
10.1093/rheumatology/ket114
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective. To evaluate the efficacy and safety of IL-1 inhibitor rilonacept (IL-1 Trap) for gout flare (GF) prevention during initiation of uric acid-lowering therapy (ULT) with allopurinol in a multiregional phase 3 clinical trial. Methods. Hyperuricaemic adults (n = 248) from South Africa, Germany and Asia with gout and two or more GFs within the past year were initiated on allopurinol and randomized 1:1:1 to once-weekly s.c. treatment with placebo (PBO), rilonacept 80 mg (R80) or rilonacept 160 mg (R160) for 16 weeks. The primary endpoint was the number of GFs per patient through week 16. Results. The population was predominantly male and racially diverse (white, 53.2%; Asian, 33.1%; black, 13.7%). Across treatments, most patients completed the study (87.8-92.9%). At 16 weeks the mean number of GFs per patient was reduced by 71.3% with R80 (0.35) and by 72.6% with R160 (0.34) relative to PBO (1.23; both P < 0.0001). The proportion of patients without GFs was higher with R80 (74.4%) and R160 (79.5%) than with PBO (43.9%; both P 0.0001), and the proportions of patients on rilonacept with multiple GFs were significantly lower (P < 0.001). Overall, the incidence of adverse events (AEs) was similar between PBO (61.0%) and rilonacept (65.1%). Injection site reactions, generally mild, were the most frequent AE with rilonacept (1.2% PBO, 12.2% R80 and 17.9% R160); none of these injection site reactions led to withdrawal. There were no study drug-related serious AEs or deaths. Conclusion. Rilonacept significantly reduced the occurrence of GFs associated with initiation of ULT, with > 70% of patients having no flares, and demonstrated an acceptable safety and tolerability profile.
引用
收藏
页码:1285 / 1292
页数:8
相关论文
共 33 条
[31]   PRELIMINARY CRITERIA FOR CLASSIFICATION OF ACUTE ARTHRITIS OF PRIMARY GOUT [J].
WALLACE, SL ;
ROBINSON, H ;
MASI, AT ;
DECKER, JL ;
MCCARTY, DJ ;
YU, TF .
ARTHRITIS AND RHEUMATISM, 1977, 20 (03) :895-900
[32]  
Weinstein S, 2010, ANN RHEUM DIS S3, V69, P605
[33]   EULAR evidence based recommendations for gout.: Part II:: Management.: Report of a task force of the EULAR standing committee for international clinical studies including therapeutics (ESCISIT) [J].
Zhang, W. ;
Doherty, M. ;
Bardin, T. ;
Pascual, E. ;
Barskova, V. ;
Conaghan, P. ;
Gerster, J. ;
Jacobs, J. ;
Leeb, B. ;
Liote, F. ;
McCarthy, G. ;
Netter, P. ;
Nuki, G. ;
Perez-Ruiz, F. ;
Pignone, A. ;
Pimentao, J. ;
Punzi, L. ;
Roddy, E. ;
Uhlig, T. ;
Zimmermann-Gorska, I. .
ANNALS OF THE RHEUMATIC DISEASES, 2006, 65 (10) :1312-1324