Evaluation of the Efficacy and Safety of Pamapimod, a p38 MAP Kinase Inhibitor, in a Double-Blind, Methotrexate-Controlled Study of Patients With Active Rheumatoid Arthritis
Evaluation of the Efficacy and Safety of Pamapimod, a p38 MAP Kinase Inhibitor, in a Double-Blind, Methotrexate-Controlled Study of Patients With Active Rheumatoid Arthritis
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DOI：
10.1002/art.24266
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发表时间：
2009-02-01
影响因子：
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通讯作者：
Caulfield, John P.
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文献类型：
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作者：
Cohen, Stanley B.;Cheng, Tien-Tsai;Caulfield, John P.
客观的。旨在确定帕马莫德（p38 MAP 激酶 a-异构体的选择性抑制剂）作为单一疗法与甲氨蝶呤 (MTX) 治疗对活动性类风湿性关节炎 (RA) 成年患者的疗效和安全性。方法。患者被随机分配到 4 个治疗组中的 1 个，并接受 12 周的双盲治疗。一组接受 MTX（7.5 毫克/周，计划升级至 20 毫克/周），3 组接受帕马莫德（50、150 或 300 毫克）每日一次。主要疗效终点是在 12 周时满足美国风湿病学会 20% 改善标准（达到 ACR20 缓解）的患者比例。次要终点包括 ACR50 和 ACR70 反应、28 个关节疾病活动评分 (DAS28) 相对于基线的变化、DAS28/欧洲抗风湿病联盟反应的分类分析，以及 ACR 核心测量集的每个参数相对于基线的变化。安全性监测包括不良事件 (AE) 记录、实验室检测、免疫学评估、心电图管理和生命体征评估。结果。分配接受 MTX 和帕马莫德治疗的患者具有相似的人口统计学和基线特征。第 12 周时，与服用 MTX 的患者 (45%) 相比，服用帕马莫德的患者出现 ACR20 反应的患者较少（50、150 和 300 mg 组分别为 23%、18% 和 31%）。次要疗效终点显示出类似的模式。不良事件通常为轻度，包括感染、皮肤病和头晕。 Pamapimod 通常耐受性良好，但 300 mg 剂量似乎比 2 个较低剂量或 MTX 毒性更大。结论。目前的结果表明，帕马莫德在治疗活动性 RA 方面不如 MTX 有效。
Objective. To determine the efficacy and safety of pamapimod (a selective inhibitor of the a-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA).Methods. Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily.The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs.Results. Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX.Conclusion. The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.