The Safety and Efficacy of a JAK Inhibitor in Patients With Active Rheumatoid Arthritis Results of a Double-Blind, Placebo-Controlled Phase IIa Trial of Three Dosage Levels of CP-690,550 Versus Placebo
The Safety and Efficacy of a JAK Inhibitor in Patients With Active Rheumatoid Arthritis Results of a Double-Blind, Placebo-Controlled Phase IIa Trial of Three Dosage Levels of CP-690,550 Versus Placebo
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DOI：
10.1002/art.24567
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发表时间：
2009-07-01
影响因子：
--
通讯作者：
Zwillich, Samuel H.
中科院分区：
文献类型：
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作者：
Kremer, Joel M.;Bloom, Bradley J.;Zwillich, Samuel H.
客观的。旨在确定 3 种不同剂量的 CP-690,550（一种有效的口服活性 JAK 抑制剂）对甲氨蝶呤、依那西普、英夫利昔单抗或阿达木单抗引起不充分或毒性反应的活动性类风湿关节炎 (RA) 患者的疗效、安全性和耐受性。方法。患者 (n = 264) 被随机随机分配接受安慰剂、5 mg CP-690,550、15 mg CP-690,550 或 30 mg CP-690,550。每天两次，持续 6 周，治疗后又随访 6 周。主要疗效终点是美国风湿病学会 20% 改善标准 (ACR20) 在 6 周时的反应率。结果。到第 6 周，每日两次 5 mg、15 mg 和 30 mg 组的 ACR20 缓解率分别为 70.5%、81.2% 和 76.8%，而安慰剂组为 29.2%（P < 0.001）。早在第 1 周，所有治疗组中就观察到与安慰剂相比，接受 CP-690,550 治疗的患者的疾病活动性有所改善。到第 4 周，所有治疗组的 ACR50 和 ACR70 反应率均显着改善。报告的最常见不良事件是头痛和恶心。 15 mg 每日两次组和 30 mg 每日两次组的感染率为 30.4%（安慰剂组为 26.2%）。没有发生机会性感染或死亡。在所有 CP-690,550 治疗组中均观察到平均低密度脂蛋白胆固醇和高密度脂蛋白胆固醇水平增加，以及平均血清肌酐水平 (0.04-0.06 mg/dl) 增加。结论。我们的研究结果表明，CP690,550 可有效治疗 RA，从而使 RA 的体征和症状迅速、具有统计学意义且具有临床意义的减少。有必要对 CP-690,550 在 RA 中的进一步研究。
Objective. To determine the efficacy, safety, and tolerability of 3 different dosages of CP-690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response.Methods. Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP-690,550, 15 mg of CP-690,550, or 30 mg of CP-690,550. twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks.Results. By week 6, the ACR20 response rates were 70.5%,81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP-690,550-treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04-0.06 mg/dl) were seen in all CP-690,550 treatment arms.Conclusion. Our findings indicate that CP690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP-690,550 in RA are warranted.