Oclacitinib (APOQUEL®) is a selective Janus kinase 1 inhibitor with efficacy in a canine model of flea allergic dermatitis.

IF 1.5 4区 农林科学 Q3 PHARMACOLOGY & PHARMACY Journal of veterinary pharmacology and therapeutics Pub Date : 2024-06-26 DOI:10.1111/jvp.13462
Andrea J Gonzales, Michelle Aleo, Sean Mahabir, James Messamore, Michael Stegemann
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Abstract

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.

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奥克替尼(APOQUEL®)是一种选择性 Janus 激酶 1 抑制剂,在犬跳蚤过敏性皮炎模型中具有疗效。
奥克替尼是一种新型 Janus 激酶 (JAK) 抑制剂,能有效抑制参与过敏、炎症和瘙痒的 JAK1 依赖性细胞因子(IL-2、IL-4、IL-6、IL-13 和 IL-31)。奥克替尼(Apoquel®,Zoetis Inc,Parsippany,NJ)被批准用于治疗/控制与过敏性皮炎相关的瘙痒症,以及治疗/控制 12 个月以上犬只特应性皮炎的临床表现。为了评估奥克替尼对跳蚤过敏性皮炎犬的疗效,在一项安慰剂对照、掩蔽、单剂量(0.4 毫克/千克)或重复剂量(0.4 毫克/千克,每天两次,连续两周)研究中对这种 JAK1 选择性抑制剂进行了测试。瘙痒行为通过视频记录进行量化,红斑和皮损通过 10 厘米视觉模拟量表(VAS)进行评估。结果显示,与安慰剂相比,奥卡替尼早在单次口服后1.5小时就能减少61%的瘙痒,用药后1-5小时平均减少85%(与安慰剂相比)(0.4 mg/kg; p
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来源期刊
CiteScore
3.10
自引率
15.40%
发文量
69
审稿时长
8-16 weeks
期刊介绍: The Journal of Veterinary Pharmacology and Therapeutics (JVPT) is an international journal devoted to the publication of scientific papers in the basic and clinical aspects of veterinary pharmacology and toxicology, whether the study is in vitro, in vivo, ex vivo or in silico. The Journal is a forum for recent scientific information and developments in the discipline of veterinary pharmacology, including toxicology and therapeutics. Studies that are entirely in vitro will not be considered within the scope of JVPT unless the study has direct relevance to the use of the drug (including toxicants and feed additives) in veterinary species, or that it can be clearly demonstrated that a similar outcome would be expected in vivo. These studies should consider approved or widely used veterinary drugs and/or drugs with broad applicability to veterinary species.
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