An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment
An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment
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DOI：
10.1016/j.jaci.2005.01.040
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发表时间：
2005-04-01
影响因子：
14.2
通讯作者：
Grossbard, EB
中科院分区：
文献类型：
--
作者：
Meltzer, EO;Berkowitz, RB;Grossbard, EB
背景：R112 抑制 Syk 激酶，Syk 激酶是通过 Fc 传递信号的转导器，是肥大细胞受体的一个元件，可阻断肥大细胞对过敏刺激的反应。 目的：在公园环境中检查鼻内 R112 与安慰剂相比，对患有症状性季节性过敏性鼻炎的志愿者的有效性和安全性。方法：在这项双盲、安慰剂对照研究中，319 名患有季节性过敏性鼻炎的志愿者于 2004 年春季在 2 个不同地点进行了为期 2 天的随机试验，其中 160 名志愿者接受鼻内 R112，159 名志愿者接受媒介对照。 32 为全身症状综合体 (GSC) 量表。评估的主要结果是 R112 和载体安慰剂之间 GSC（8 小时内曲线下面积）相对于基线减少的差异。结果：在基线时，组合 GSC 类似于 18/32，并且治疗组之间相等。 8 小时后（每 4 小时给药 3 毫克/鼻孔 X 2），与安慰剂相比，R112 显着降低了 GSC（分别为 7 单位和 5.4 单位；P = .0005）。与对照组相比，R112 组中组合形成 GSC 的每种单独症状也显着改善（P < .05）。早在给药后 45 分钟，R112 就表现出较安慰剂明显改善的症状，且作用持续时间超过 4 小时。各组之间的不良反应无法区分，并且在临床上不显着。结论：鼻内 R112 在这项公园研究中是有效的，是一种有前途的季节性过敏性鼻炎新疗法。
Background: R112 inhibits Syk kinase, a transducer of signaling through the Fc is an element of receptor of mast cells, blocking mast cell responses to allergic stimuli.Objective: Examine the efficacy and safety of intranasal R112 in volunteers with symptomatic seasonal allergic rhinitis compared with a placebo in a park setting. Methods: In this double-blind, placebo-controlled study of 319 volunteers with seasonal allergic rhinitis, 160 were randomized to intranasal R112 and 159 to a vehicle control during 2 days at 2 separate locations in spring 2004. Subjects were evaluated for symptoms of allergic rhinitis (ie, sneezes, runny nose/sniffles, itchy nose, stuffy nose) on the basis of a possible maximum score of 32 for the Global Symptom Complex (GSC) scale. The primary outcome evaluated was the difference in the reduction in GSC (area under the curve over a period of 8 hours) from baseline between R112 and vehicle placebo.Results: At baseline, the combined GSC was similar to 18/32 and equal between treatment groups. After 8 hours (dosing 3 mg/nostril every 4 hours X 2), R112 significantly reduced the GSC compared with placebo (7 vs 5.4 units, respectively; P = .0005). Each individual symptom combined to form the GSC was also significantly improved in the R112 group compared with control (P < .05). As early as 45 minutes after dosing, R112 showed a significant improvement in symptoms over placebo, and the duration of action exceeded 4 hours. Adverse effects were indistinguishable between the groups and clinically insignificant.Conclusion: Intranasal R112 was effective in this park study and is a promising new treatment for seasonal allergic rhinitis.