A&R：IP-10单抗MDX-1100治疗甲氨蝶呤疗效不佳的RA有效

CXCL-10（也是一种诱生干扰素-γ的10-kd 蛋白[IP-10]）是一种趋化因子，在类风湿关节炎（RA）免疫发病机制中发挥潜在作用。来自美国新泽西州布卢姆斯伯里Medarex公司的Michael Yellin等人进行了一项研究。该Ⅱ阶段研究的目的是评价对甲氨蝶呤（MTX）疗效不完全的RA患者接受MDX-1100治疗的有效性和安全性，MDX-1100是一种全人源性的抗-CXCL10（抗-IP-10）的单克隆抗体。研究结果在线发布在2012年6月的《关节炎与风湿病》（ARTHRITIS & RHEUMATISM）杂志上，作者发现，MDX-1100耐受性良好，经证实对MTX疗效不完全的RA患者有良好的临床疗效，IP-10在RA的免疫发病机制中的发挥潜在作用。

接受稳定剂量的MTX（10-25mg/周）的活动性RA患者被随机分配静脉使用10mg/kg MDX-1100(n=35)或者安慰剂（n=35），频率是每两周一次。主要终点是在第85天时获得美国风湿病学院20%改善标准（获得ACR20缓解）的患者比例，针对患者安全性的随访直至第141天。

研究结果如下，接受MDX-1100治疗组的患者获得ACR20缓解的概率显著高于安慰剂对照组（54% vs 17%；P=0.0024）。治疗组之间的ACR20缓解率自第43天起可观察到统计学显著差异（P<0.05）。第85天时两组之间的ACR50和ACR70缓解率无显著差异。总的来说，有51.4%的MDX-1100治疗患者和30.3%的安慰剂治疗患者出现至少一项不良反应事件（AE）。整个研究中，药物相关的严重AEs未有报道。

研究发现，MDX-1100耐受性良好，经证实对MTX疗效不完全的RA患者有良好的临床疗效。该研究首次证实了一种趋化因子抑制剂对RA的疗效，并为IP-10在RA的免疫发病机制中发挥潜在作用的观点提供了依据。

A phase II, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of MDX-1100, a fully human anti-CXCL10 monoclonal antibody, in combination with methotrexate in patients with rheumatoid arthritis.
OBJECTIVE
CXCL10 (also known as interferon-γ-inducible 10-kd protein [IP-10]) is a chemokine that potentially plays a role in the immunopathogenesis of rheumatoid arthritis (RA). We undertook this phase II study to evaluate the efficacy and safety of MDX-1100, a fully human, anti-CXCL10 (anti-IP-10) monoclonal antibody, in RA patients whose disease responded inadequately to methotrexate (MTX).
METHODS
Patients with active RA receiving stable doses of MTX (10-25 mg weekly) were randomized to receive intravenous doses of 10 mg/kg MDX-1100 (n = 35) or placebo (n = 35) every other week. The primary end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) on day 85, and patients were followed up for safety to day 141.
RESULTS
The ACR20 response rate was significantly higher among MDX-1100-treated patients than among placebo-treated patients (54% versus 17%; P = 0.0024). Statistically significant differences in the ACR20 response rate between treatments were observed starting on day 43 (P < 0.05). The ACR50 and ACR70 response rates on day 85 did not differ between the groups. Overall, 51.4% of MDX-1100-treated patients and 30.3% of placebo-treated patients experienced at least 1 adverse event (AE). No study drug-related serious AEs were reported.
CONCLUSION
MDX-1100 was well tolerated and demonstrated clinical efficacy in RA patients whose disease responded inadequately to MTX. This is the first study to demonstrate clinical efficacy of a chemokine inhibitor in RA and supports the notion of a potential role of IP-10 in the immunopathogenesis of RA.