依奇珠单抗治疗活动性银屑病关节炎患者的疗效和安全性：一项 III 期研究（SPIRIT-P1）的 52 周结果。
Efficacy and Safety of Ixekizumab in Patients with Active Psoriatic Arthritis: 52-week Results from a Phase III Study (SPIRIT-P1).
机构信息
From the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands; Division of Rheumatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Immuno-Rheumatology Center, St. Luke's International Hospital, St. Luke's International University, Tokyo, Japan; Eli Lilly and Company, Indianapolis, Indiana, USA; Laboratoires Lilly France, Neuilly, France; Department of Rheumatology, Swedish Medical Center; University of Washington, Seattle, Washington, USA.
D. van der Heijde has received consulting fees from AbbVie and Eli Lilly and Company. D.D. Gladman has received grants or consulting fees from AbbVie and Eli Lilly and Company. M. Kishimoto received honoraria and advisory fees from AbbVie and Eli Lilly and Company. S. Rathmann, S. Moriarty, C. Shuler, and H. Carlier are employees and stockholders of Eli Lilly and Company. O. Benichou is an employee and stockholder of Laboratoires Lilly France. P.J. Mease has received research grants and has been a consultant and/or speaker for AbbVie and Eli Lilly and Company.
出版信息
J Rheumatol. 2018 Mar;45(3):367-377. doi: 10.3899/jrheum.170429. Epub 2017 Dec 15.
OBJECTIVE
To evaluate the efficacy and safety of ixekizumab (IXE), an interleukin 17A antagonist, in patients with psoriatic arthritis (PsA) after 52 weeks in a phase III study.
METHODS
Patients were initially randomly assigned to IXE 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after a 160-mg starting dose, placebo (PBO), or adalimumab (ADA) 40 mg Q2W. At Week 24 (Week 16 for inadequate responders), ADA (8-week washout before starting IXE) and PBO patients were rerandomized to IXEQ2W or IXEQ4W. Six treatment groups were evaluated in the extension period (weeks 24-52): IXEQ2W/IXEQ2W, IXEQ4W/IXEQ4W, ADA/IXEQ2W, ADA/IXEQ4W, PBO/IXEQ2W, and PBO/IXEQ4W. The extension period population (EPP) included patients who received ≥ 1 dose of study medication during the extension period.
RESULTS
There were 381/417 (91.4%) patients who entered the extension period. In the IXEQ4W/IXEQ4W and IXEQ2W/IXEQ2W groups (EPP), respectively, American College of Rheumatology (ACR)20 (69.1% and 68.8%), ACR50 (54.6% and 53.1%), and ACR70 (39.2% and 39.6%) response rates were sustained at Week 52. Patients rerandomized to IXE also demonstrated efficacy measured by ACR response rates at Week 52. A similar pattern was observed for Psoriasis Area and Severity Index outcomes. Radiographic progression in all 6 groups was minimal. The most frequently reported treatment-emergent adverse events (≥ 4%) were nasopharyngitis, injection site reaction, injection site erythema, upper respiratory tract infection, and back pain. No deaths were reported, and serious adverse event frequency was 0-4% with IXE.
CONCLUSION
During the extension period, IXEQ4W or IXEQ2W treatment demonstrated sustained efficacy in key PsA domains with a safety profile consistent with other studies investigating IXE. Clinical trial number: NCT01695239; EudraCT 2011-002326-49.
目的
评估白细胞介素 17A 拮抗剂依奇珠单抗（IXE）在一项 III 期研究中对银屑病关节炎（PsA）患者的疗效和安全性，随访 52 周。
方法
患者最初随机分为 IXE80mg 每 2 周（IXEQ2W）或每 4 周（IXEQ4W）组、安慰剂（PBO）组或阿达木单抗（ADA）40mg 每 2 周（ADAQ2W）组，给药前给予 160mg 起始剂量。在第 24 周（应答不足患者为第 16 周），ADA（IXE 治疗前 8 周洗脱期）和 PBO 患者重新随机分为 IXEQ2W 或 IXEQ4W 组。在扩展期（第 24-52 周）评估了 6 个治疗组：IXEQ2W/IXEQ2W、IXEQ4W/IXEQ4W、ADA/IXEQ2W、ADA/IXEQ4W、PBO/IXEQ2W 和 PBO/IXEQ4W。扩展期人群（EPP）包括在扩展期接受至少 1 剂研究药物的患者。
结果
共有 417 例患者中的 381 例（91.4%）进入扩展期。在 IXEQ4W/IXEQ4W 和 IXEQ2W/IXEQ2W 组（EPP）中，美国风湿病学会（ACR）20 应答率分别为 69.1%和 68.8%、ACR50 应答率分别为 54.6%和 53.1%、ACR70 应答率分别为 39.2%和 39.6%，在第 52 周时均保持持续应答。重新随机分配至 IXE 的患者在第 52 周时也表现出 ACR 应答率的疗效。在所有 6 个组中，均观察到类似的 PsA 面积和严重程度指数结果模式。所有 6 个组的放射学进展均较小。最常见的治疗后不良事件（发生率≥4%）为鼻咽炎、注射部位反应、注射部位红斑、上呼吸道感染和背痛。未报告死亡事件，IXE 的严重不良事件发生率为 0-4%。
结论
在扩展期内，IXEQ4W 或 IXEQ2W 治疗在关键的 PsA 领域中表现出持续的疗效，安全性与其他研究 IXE 的研究一致。临床试验编号：NCT01695239；EudraCT 编号：2011-002326-49。
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