Objective To evaluate the efficacy, biological activity and safety of tregalizumab in patients with active rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). Methods 321 patients were randomised (1:1:1:1) to placebo or tregalizumab 25, 100 or 200 mg once-weekly subcutaneously in addition to MTX treatment. Responders at week 12 continued the same treatment, and non-responders at week 12 were escalated to the next higher tregalizumab dose level or re-randomised from placebo to active treatment. After 24 weeks, patients could continue treatment with tregalizumab for 24 weeks (extension phase). The primary endpoint was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. Safety and biological activity were monitored through week 48. Results At week 12, ACR20 response rates were not statistically significantly different between placebo and any of the tregalizumab doses. Tregalizumab injections were well tolerated; most adverse events were mild to moderate and comparable among treatment and placebo groups. Biological activity was shown by dose-dependent CD4 downmodulation. Conclusion Treatment with tregalizumab did not show significant clinical efficacy in patients with active RA compared with placebo but resulted in the expected biological effect on CD4 modulation. Tregalizumab was generally well tolerated, and no new safety findings were identified. Trial registration number NCT01999192; Results.

中文翻译：

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tregalizumab 在类风湿性关节炎和甲氨蝶呤反应不足的患者中的疗效和安全性：一项 IIb 期、随机、安慰剂对照试验的结果

目的 评价 tregalizumab 治疗活动性类风湿性关节炎（RA）和甲氨蝶呤（MTX）反应不足的患者的疗效、生物活性和安全性。方法 321 名患者随机（1:1:1:1）接受安慰剂或 tregalizumab 25、100 或 200 mg 每周一次皮下注射以及 MTX 治疗。第 12 周的反应者继续相同的治疗，第 12 周的无反应者被升级到下一个更高的 tregalizumab 剂量水平或从安慰剂重新随机分配到积极治疗。24 周后，患者可以继续接受 tregalizumab 治疗 24 周（延长期）。主要终点是第 12 周美国风湿病学会 20% 改善标准 (ACR20) 的反应率。在第 48 周监测安全性和生物活性。 结果 在第 12 周，ACR20 反应率在安慰剂和任何 tregalizumab 剂量之间没有统计学显着差异。Tregalizumab 注射的耐受性良好；大多数不良事件为轻度至中度，治疗组和安慰剂组之间具有可比性。生物活性由剂量依赖性 CD4 下调显示。结论 与安慰剂相比，tregalizumab 治疗在活动性 RA 患者中没有显示出显着的临床疗效，但对 CD4 调节产生了预期的生物学效应。Tregalizumab 总体耐受性良好，未发现新的安全性发现。试验注册号NCT01999192；结果。大多数不良事件为轻度至中度，治疗组和安慰剂组之间具有可比性。生物活性由剂量依赖性 CD4 下调显示。结论 与安慰剂相比，tregalizumab 治疗在活动性 RA 患者中没有显示出显着的临床疗效，但对 CD4 调节产生了预期的生物学效应。Tregalizumab 总体耐受性良好，未发现新的安全性发现。试验注册号NCT01999192；结果。大多数不良事件为轻度至中度，治疗组和安慰剂组之间具有可比性。生物活性由剂量依赖性 CD4 下调显示。结论 与安慰剂相比，tregalizumab 治疗在活动性 RA 患者中没有显示出显着的临床疗效，但对 CD4 调节产生了预期的生物学效应。Tregalizumab 总体耐受性良好，未发现新的安全性发现。试验注册号NCT01999192；结果。并且没有发现新的安全性发现。试验注册号NCT01999192；结果。并且没有发现新的安全性发现。试验注册号NCT01999192；结果。