Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis.
Brief Report: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled, Multiple-Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis.
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DOI：
10.1002/art.40479
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Chung JB
中科院分区：
文献类型：
--
作者：
Cheng LE;Amoura Z;Cheah B;Hiepe F;Sullivan BA;Zhou L;Arnold GE;Tsuji WH;Merrill JT;Chung JB
目的：评价抗诱导性T细胞共刺激分子配体(ICOSL)的全人抗体AMG-557治疗系统性红斑狼疮(SLE)合并关节炎的安全性和潜在疗效。在这项Ib期的随机、双盲、安慰剂对照试验中，患者每周服用AMG557210毫克(n=10)或安慰剂(n=10)，持续3周，然后每隔一周再服用10剂。到第85天，皮质类固醇剂量逐渐减少到≤7.5 mg/d，到第29天停用免疫抑制剂。第169天的主要终点是安全性、免疫原性、狼疮性关节炎反应指数(LAI；由关节压痛和肿胀计数减少定义)、不列颠群岛狼疮评估组织(BILAG)指数肌肉骨骼领域的≥1字母改善以及停药。次要/探查终点是关节压痛和肿胀计数、BILAG指数(肌肉骨骼，全球)和系统性红斑狼疮疾病活动指数(SLEDAI)的变化。不良事件的发生率在不同组之间是相似的，其中大多数是轻微的。服用AMG-557的10名患者中有3名出现Lari反应，接受安慰剂治疗的10名患者中有1名出现Lari反应(P=0.58)。与安慰剂组(2/10)相比，更多的患者在第169天的≥评分中获得了4分的改善(7/10)(P=0.07)。服用AMG 557(与安慰剂相比)的患者在第169天的全球BILAG指数得分(-36.3%比-24.7%)和SLEDAI得分(-47.8%比-10.7%)以及关节压痛(-22.8%比-13.5%)和肿胀(-62.1%比-7.8%)方面比基线有更大的改善。AMG-557显示出安全性和潜在疗效，支持进一步评估ICOSL阻断对SLE患者的临床疗效。
To evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis. In this phase Ib, randomized, double‐blind, placebo‐controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1‐letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4‐point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (–36.3% versus –24.7%) and the SLEDAI score (–47.8% versus –10.7%) and in tender (–22.8% versus –13.5%) and swollen (–62.1% versus –7.8%) joint counts on day 169. AMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.
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影响因子：
9.1
作者：
Robertson N;Engelhardt KR;Morgan NV;Barge D;Cant AJ;Hughes SM;Abinun M;Xu Y;Koref MS;Arkwright PD;Hambleton S
通讯作者：
Hambleton S
DOI：
10.1038/nrrheum.2012.58
发表时间：
2012-05-01
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
Sullivan BA;Tsuji W;Kivitz A;Peng J;Arnold GE;Boedigheimer MJ;Chiu K;Green CL;Kaliyaperumal A;Wang C;Ferbas J;Chung JB
通讯作者：
Chung JB
系统性红斑狼疮
影响因子：
81.5
作者：
Kaul, Arvind;Gordon, Caroline;Hughes, Graham
通讯作者：
Hughes, Graham
影响因子：
168.9
作者：
Lisnevskaia, Larissa;Murphy, Grainne;Isenberg, David
通讯作者：
Isenberg, David