Oclacitinib是一种新型Janus激酶(JAK)抑制剂,可有效抑制参与过敏的JAK1依赖性细胞因子,炎症,和瘙痒(IL-2、IL-4、IL-6、IL-13和IL-31)。Oclacitinib(Apoquel®,ZoetisInc,Parsippany,NJ)被批准用于治疗/控制与过敏性皮炎相关的瘙痒和治疗/控制至少12月龄狗的特应性皮炎的临床表现。评价奥拉替尼治疗犬跳蚤过敏性皮炎的疗效,JAK1选择性抑制剂在安慰剂对照中进行了测试,蒙面,单剂量(0.4mg/kg)或重复剂量(0.4mg/kg,每天两次,共2周)研究。通过录像对瘙痒行为进行定量,使用10厘米视觉模拟量表(VAS)评估红斑和皮肤病变。结果显示,与安慰剂相比,奥克拉替尼早在单次口服剂量后1.5小时将瘙痒减少61%,给药后1-5小时平均减少85%(与安慰剂相比)(0.4mg/kg;p<.0001)。在重复剂量研究中,与安慰剂相比,奥克替尼在第14天还显著降低了红斑(p<.0001)和皮肤损伤(p<.0005)的VAS评分。在进行这些研究期间没有发现不良事件。大多数狗在跳蚤侵染后IL-31浓度升高,提示JAK1依赖性细胞因子可能导致跳蚤变态反应性皮炎的临床症状.这些研究结果表明,奥克拉替尼,与变态反应和炎症有关的JAK1依赖性细胞因子抑制剂可以迅速减少与狗跳蚤过敏性皮炎相关的临床症状.
Oclacitinib is a novel Janus kinase (JAK) inhibitor that potently inhibits
JAK1-dependent cytokines involved in allergy, inflammation, and pruritus (IL-2, IL-4, IL-6, IL-13, and IL-31). Oclacitinib (Apoquel®, Zoetis Inc, Parsippany, NJ) is approved for the treatment/control of pruritus associated with allergic dermatitis and treatment/control of clinical manifestations of atopic dermatitis in dogs at least 12 months of age. To evaluate the effectiveness of oclacitinib in dogs with flea allergy dermatitis, the
JAK1 selective inhibitor was tested in a placebo-controlled, masked, single-dose (0.4 mg/kg) or repeat-dose (0.4 mg/kg, twice daily for 2 weeks) study. Pruritic behaviors were quantitated by video recording, and erythema and skin lesions were assessed using a 10-cm visual analog scale (VAS). Results showed that oclacitinib reduced pruritus by 61% as early as 1.5 h after a single oral dose compared to placebo, with an average reduction (compared to placebo) of 85% 1-5 h after dosing (0.4 mg/kg; p < .0001). Oclacitinib also significantly reduced erythema (p < .0001) and skin lesion (p < .0005) VAS scores on Day 14 compared to placebo in a repeat dose study. No adverse events were noted during the conduct of these studies. IL-31 concentrations were elevated in the majority of dogs after flea infestation, suggesting
JAK1-dependent cytokines may drive clinical signs of flea allergy dermatitis. These findings show that oclacitinib, an inhibitor of
JAK1-dependent cytokines involved in allergy and inflammation can rapidly reduce clinical signs associated with flea allergic dermatitis in dogs.