Phase II Study of Tofacitinib (CP-690,550) Combined With Methotrexate in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
Phase II Study of Tofacitinib (CP-690,550) Combined With Methotrexate in Patients With Rheumatoid Arthritis and an Inadequate Response to Methotrexate
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DOI：
10.1002/acr.20494
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发表时间：
2011-08-01
影响因子：
4.7
通讯作者：
Zwillich, Samuel H.
中科院分区：
文献类型：
--
作者：
Tanaka, Yoshiya;Suzuki, Makoto;Zwillich, Samuel H.
客观的。比较 4 剂口服托法替布 (CP-690,550) 与安慰剂对接受稳定背景甲氨蝶呤 (MTX) 且对单独 MTX 反应不足的日本活动性类风湿关节炎 (RA) 患者的疗效、安全性和耐受性。方法。在这项为期 12 周的 II 期双盲研究中，共有 140 名患者被随机分配接受托法替布 1、3、5 和 10 毫克每天两次或安慰剂治疗。所有患者均继续使用背景 MTX。在第 1、2、4、8 和 12 周评估疗效和安全性。主要疗效终点是第 12 周时美国风湿病学会 20% 改善标准 (ACR20) 的缓解率。 结果。所有托法替布治疗组在第 12 周时的 ACR20 缓解率均显着 (P < 0.0001)：1 mg 每天两次，64.3%； 3毫克，每日两次，77.8%； 5毫克，每日两次，96.3%；每天两次 10 毫克，有效率为 80.8%，而安慰剂为 14.3%。观察到 ACR20 存在显着的剂量反应关系 (P < 0.0001)。托法替布 10 mg 每天两次，第 12 周时，72.7% 的高基线疾病活动患者实现了低疾病活动（P < 0.0001）。 ACR50、ACR70、健康评估问卷残疾指数和疾病活动评分 28-3（C 反应蛋白）也有显着改善。最常见的不良事件 (AE) 是鼻咽炎 (n = 13) 以及丙氨酸转氨酶 (n = 12) 和天冬氨酸转氨酶 (n = 9) 水平升高。这些 AE 的严重程度为轻度或中度。 5 名患者报告了严重的 AE。没有发生死亡。结论。在对 MTX 反应不足的日本活动性 RA 患者中，托法替布联合 MTX 12 周有效，且安全性可控。
Objective. To compare the efficacy, safety, and tolerability of 4 doses of oral tofacitinib (CP-690,550) with placebo in Japanese patients with active rheumatoid arthritis (RA) receiving stable background methotrexate (MTX) who had an inadequate response to MTX alone.Methods. A total of 140 patients were randomized to receive tofacitinib 1, 3, 5, and 10 mg twice a day or placebo in this 12-week, phase II, double-blind study. All patients remained on background MTX. Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12.Results. ACR20 response rates at week 12 were significant (P < 0.0001) for all tofacitinib treatment groups: 1 mg twice a day, 64.3%; 3 mg twice a day, 77.8%; 5 mg twice a day, 96.3%; and 10 mg twice a day, 80.8% versus placebo, 14.3%. A significant dose-response relationship for the ACR20 was observed (P < 0.0001). Low disease activity was achieved by 72.7% of patients with high baseline disease activity for tofacitinib 10 mg twice a day at week 12 (P < 0.0001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, and Disease Activity Score 28-3 (C-reactive protein) were also reported. The most commonly reported adverse events (AEs) were nasopharyngitis (n = 13) and increased alanine aminotransferase (n = 12) and aspartate aminotransferase (n = 9) levels. These AEs were mild or moderate in severity. Serious AEs were reported by 5 patients. No deaths occurred.Conclusion. In Japanese patients with active RA with an inadequate response to MTX, tofacitinib in combination with MTX over 12 weeks was efficacious and had a manageable safety profile.