0.0584%氢化可的松醋丙酯喷雾剂治疗猫过敏性皮肤病的疗效:一项标 ...

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Efficacy of a 0.0584% hydrocortisone aceponate spray in presumed feline allergic dermatitis: an open label pilot study

0.0584%氢化可的松醋丙酯喷雾剂治疗猫过敏性皮肤病的疗效:一项标签外试点研究

作者：Vanessa Schmidt, Laura M. Buckley, Neil A. McEwan, Christophe A. Re`me and Tim J. Nuttall

 

Abstract

摘要

This study evaluated the efficacy of a 0.0584% hydrocortisone aceponate (HCA) spray (Cortavance ; Virbac SA) in 10 cats with presumed allergic dermatitis. The cats initially received two sprays ⁄ 100 cm2 of skin once daily. Clinical lesions (a Feline Dermatitis Extent and Severity Index; FeDESI), pruritus (10 cm visual analog scale with grade descriptors) and owner assessments of efficacy, tolerance and ease of use (from 1 = very poor to 5 = excellent) were assessed every 14 days. The frequency of treatment was reduced after day 28 in cats with a >50% reduction in FeDESI and pruritus scores. One cat was lost to follow up at day 28 and two at day 42. Intention-to-treat data were analysed. The FeDESI [mean (SD): day 0, 42.2 (15.7) and day 56, 9.9 (11.7); P < 0.0001] and pruritus scores [day 0, 61.2 mm (20.1) and day 56, 14.6 mm (16.1); P < 0.0001] significantly decreased throughout the trial. The owner scores for tolerance [median (range): day 14, 4 (1–5) and day 56, 4 (3–5); P = 0.003] and ease of administration [day 14, 3 (2–5) and day 56, 4 (2–5); P = 0.02] significantly increased during the trial, but there was no significant change in efficacy scores [day 14, 4 (3–5) and day 56, 4 (2–5); P = 0.5]. There were no adverse effects attributable to the HCA spray, no significant changes in weight [mean (SD): day 0, 5.0 kg (1.4) and day 56, 5.0 kg (1.6); P = 0.51] and no significant changes in haematology, biochemistry or urinalysis (n = 4). Six cats required every-other-day treatment and four required daily treatment. In conclusion, HCA spray appeared to be effective and safe in these cats, although it is not licensed for use in this species.

本研究评估了0.0584%氢化可的松醋丙酯(HCA)喷雾剂(皮乐美)在10只推测为过敏性皮肤病猫的疗效。最初，这些猫每100平方厘米2 按压2泵，每天一次皮肤喷雾剂。临床病变(a)猫皮肤病程度及严重程度指数（FeDESI)，每14天评估一次、瘙痒(10 cm视觉模拟量表，并附有等级描述）和宠主疗效评估、耐受性和易用性的评估(从1 =非常差到5 =优秀)。第28天后，治疗频率降低，猫的FeDESI和瘙痒评分降低>50%。第28天和第42天分别失1只和2只。分析意向治疗数据。FeDESI[平均(SD):第0天，42.2(15.7)天和第56天，9.9 (11.7);P < 0.0001]和瘙痒评分[第0天，61.2 mm(20.1)和第56天，14.6 mm (16.1);P < 0.0001]在整个试验过程中显著降低。宠主容忍度评分[中位数(范围):第14,4天(1-5)和第56,4天(3-5);P = 0.003]和给药难易程度[第14、3(2-5)天和第56、4(2-5)天];P = 0.02]在试验期间显著升高，但疗效评分无显著变化[第14,4(3-5)天和第56,4(2-5)天];P = 0.5]。无不良反应可归因于HCA喷雾，体重无显著变化[平均(SD):第0天，5.0 kg(1.4)和第56天，5.0 kg (1.6);P = 0.51]，血液学、生物化学和尿液分析均无显著变化(n = 4)。6只猫需要每隔一天治疗一次，4只猫需要每天治疗一次。总之，HCA喷雾剂在这些猫上似乎是有效和安全的，但此药没有被许可用于猫。

 

Introduction

介绍

Feline allergic dermatitis is a common inflammatory and pruritic skin condition. Frequently recognized manifestations include head and neck dermatitis, eosinophilic granuloma, eosinophilic plaque and military dermatitis, and individual cats may exhibit any combination of these clinical patterns. The diagnosis is based on the history and clinical signs, excluding other causes of these lesions, such as flea allergic dermatitis, mosquito bites, other ectoparasites, cutaneous adverse food reactions, psychogenic dermatitis and hypereosinophilic syndrome.

猫过敏性皮肤病是一种常见的炎症和瘙痒性皮肤疾病。常见的症状包括头颈部皮肤病、嗜酸性肉芽肿、嗜酸性斑块和粟粒性皮炎，个别猫可能表现出这些临床模式的任何组合。诊断依据病史和临床症状，排除引起这些病变的其他病因，如跳蚤过敏性皮肤病、蚊虫叮咬、其他体外寄生虫、皮肤食物不良反应、心因性皮肤病和嗜酸性粒细胞增多综合征。

 

Various treatments have been used to treat feline allergic skin disease. Some cats with positive environmental allergen-specific tests respond well to allergen-specific immunotherapy, although the evidence for efficacy and safety is less good than that for dogs. Many cats nevertheless require anti-inflammatory treatment. Traditionally, oral or parenteral glucocorticoids were most frequently used, but concerns over long-term safety have prompted exploration of alternative treatments. Data on the efficacy of antihistamines and essential fatty acids are limited, and they are not considered potent anti-inflammatory agents. Ciclosporin is highly effective for the treatment of feline atopic dermatitis (AD) and eosinophilic granuloma complex.  It appears to be well tolerated, with most adverse effects limited to mild gastrointestinal upsets.  Immunosuppression, however, could lead to systemic toxoplasmosis, viral infections or neoplasia.  The risk at the doses used to treat feline AD appears to be small,10–12,16 but there is an unmet need for a safe and efficacious anti-inflammatory treatment option for cats with inflammatory and ⁄ or pruritic dermatoses.

各种治疗方法已经被用来治疗猫过敏性皮肤病。一些环境过敏原特异性测试呈阳性的猫对过敏原特异性免疫疗法反应良好，但疗效和安全性的证据不如犬。然而，许多猫需要抗炎治疗。传统上，口服或注射糖皮质激素是最常用的，但对长期安全性的担忧促使人们探索替代治疗方法。关于抗组胺药和必需脂肪酸功效的数据有限，它们不被认为是有效的抗炎剂。环孢素对治疗猫特应性皮肤病(AD)和嗜酸性肉芽肿复合物非常有效。它似乎耐受性良好，大多数不良反应仅限于轻微的胃肠道不适。然而，免疫抑制可能导致全身性弓形虫病、病毒感染或肿瘤。用于治疗猫AD的剂量的风险似乎很小，但对于患有炎症性或瘙痒性皮肤病的猫来说，安全有效的抗炎治疗选择的需求尚未得到满足。

 

The topical diester glucocorticoid hydrocortisone aceponate (HCA; Cortavance ; Virbac SA, Carros, France) is licensed in a 0.0584% spray formulation for up to 70 days treatment of pyotraumatic dermatitis, flea allergic dermatitis and other inflammatory dermatoses in dogs. Nonhalogenated, diester topical glucocorticoids avoid many of the adverse effects seen with traditional topical glucocorticoids by virtue of their metabolism into largely inactive moieties within the skin. This is associated with better local and systemic tolerance, enhanced penetration of the stratum corneum and increased anti-inflammatory potency. Two randomized, placebo-controlled trials (RCTs) demonstrated good efficacy in canine AD, and a further single-blind RCT showed similar efficacy to ciclosporin. Hydrocortisone aceponate appears to be well tolerated; no adverse effects were seen after 70–84 days treatment in the RCTs  or after 8 weeks treatment of healthy dogs, but a significant decrease in dermal thickness was noted after 14 days treatment in another study. Recent practice guidelines recommended the use of this product in managing both acute and chronic canine AD. The aim of this open-label pilot study was to provide preliminary proof-of-concept evidence that HCA could be used to manage presumed feline allergic dermatitis.

外用二酯糖皮质激素氢化可的松醋丙酯(HCA;皮乐美)，0.0584%喷雾制剂可用于治疗犬的脓性创伤性皮肤病、跳蚤过敏性皮肤病和其他炎症性皮肤病，最长可达70天。非卤化、双酯外用糖皮质激素避免了传统外用糖皮质激素的许多副作用，因为它们在皮肤内代谢成大部分不活跃产物。这与更好的外用和全身耐受性，增强角质层渗透和增强抗炎效力有关。两项随机、安慰剂对照试验(RCT)显示出对犬AD的良好疗效，另一项单盲RCT显示出与环孢素相似的疗效。氢化可的松醋丙酯似乎耐受性良好;在随机对照试验中，70-84天的治疗或8周的健康犬治疗后没有发现不良反应，但在另一项研究中，14天的治疗后皮肤厚度显著减少。最近的实践指南建议使用本产品管理急性和慢性犬AD。这项标签外试点研究的目的是提供初步的概念证明证据，证明HCA可用于治疗推测的猫过敏性皮肤病。

 

Materials and methods

材料与方法

Study patients

研究的病患

The study was performed in accordance with ethical guidelines laid down by The University of Liverpool and Virbac SA. Ten cats with perennial inflammatory and pruritic dermatoses [head and neck dermatitis with trunk miliary dermatitis (2), eosinophilic plaque of the ventral abdomen and medial limbs (7), and trunk miliary dermatitis (1)] were diagnosed with presumed allergic dermatitis based on their history, clinical signs, cytology and exclusion of other skin diseases. Hair plucks, skin scrapes and fungal cultures were normal. There was no response to an 8 week flea control trial with on-animal [selamectin spot-on (Stronghold ; Pfizer Animal Health, Sandwich, UK; three treatments, once every 14 days) in six cats, and imidacloprid ⁄ moxidectin spot-on (Advocate ; Bayer Animal Health, Newbury, UK; three treatments, once every 14 days) in four cats] and environmental treatment [one application of a permethrin ⁄ piperonyl butoxide ⁄ pyriproxifen spray (Indorex ; Virbac Animal Health, Bury St Edmunds, UK)], and a food trial with novel home-cooked (n = 1), novel commercial (n = 3) or hydrolysed proteins (n = 6). Three cats completed an 8 week food trial, but the food trials had to be abandoned early in the remaining cats (after 3 weeks in four cats, 4 weeks in two cats and 5 weeks in one cat). None of the cats had a history or clinical signs compatible with a pyschogenic dermatosis. Drug withdrawal periods were as follows: topical or systemic antimicrobials, 7 days; oral glucocorticoids, 28 days; parenteral glucocorticoids, 56 days; antihistamines, 14 days; and ciclosporin, 28 days. None of the cats had been treated with allergen-specific immunotherapy or essential fatty acids. The cats were maintained on their usual diets, and regular flea control [selamectin, n = 5; imidacloprid ⁄ moxidectin, n = 2; or fipronil ⁄ s-methoprene (Frontline Combo ; Merial Animal Health, Harlow, UK) spot-on every 28 days]. No other treatments were permitted.

这项研究是按照利物浦大学和Virbac SA制定的道德准则进行的。10只患有全年性炎症性瘙痒性皮肤病的猫[头颈部皮肤病合并躯干粟粒性皮炎(2)、腹侧及四肢内侧嗜酸性斑块(7)、躯干粟粒性皮炎(1)]，根据病史、临床症状、细胞学检查及排除其他皮肤病诊断为过敏性皮肤病。毛发镜检、皮肤刮片和真菌培养均正常。在8周的跳蚤控制试验中，动物身上使用赛拉菌素，对6只猫进行3次治疗，每14天1次)，并使用吡虫啉/莫西克丁，对四只猫进行三次治疗，每14天一次)和环境治疗[一次使用氯菊酯/胡椒酰丁醇/吡呋昔芬喷雾，并进行了一项食物排查试验，包括新型自制蛋白质(n = 1)、新型商业蛋白质(n = 3)或水解蛋白质(n = 6)。三只猫完成了为期8周的食物试验，但其余猫的食物试验必须提前放弃(四只猫3周，两只猫4周，一只猫5周)。所有猫均无与心因性皮肤病相关的病史或临床症状。停药期如下:外用或全身抗菌药物，7天;口服糖皮质激素，28天;注射糖皮质激素56天;抗组胺药，14天;环孢素，28天。没有一只猫接受过过敏原特异性免疫疗法或必需脂肪酸的治疗。猫维持正常饮食，并定期控制跳蚤[赛拉菌素, n = 5;吡虫啉/莫昔克丁，n = 2;或氟虫腈/ s-甲氧普烯，每28天一次。不允许进行其他治疗。

 

Trial protocol

试验协议

The owners applied the HCA spray once daily to affected skin (two sprays from 10 cm per 100 cm2 of affected skin). Hydrocortisone aceponate was wiped onto head lesions using cotton wool if necessary. Full clinical assessments were performed on days 0, 14, 28, 42 and 56. Clinical lesions were scored using a Feline Dermatitis Extent and Severity Index (FeDESI; Figure 1).26 The owners assessed pruritus using a 10 cm visual analog scale with grade descriptors.  From day 14, the owners independently scored ease of use, tolerance and efficacy from 1 (very poor) to 5 (excellent). The cats were weighed at each visit, and blood and urine samples were collected from four cats on days 0 and 56. It was not possible to collect adequate samples from the remaining cats conscious, and it was decided to not sedate the cats for sampling, unless their condition warranted further investigation. The owners recorded the number of sprays administered, adverse events, concomitant treatments and other information in a daily diary.

主人将HCA喷雾剂每天一次喷在病变皮肤上(每100平方厘米距离10厘米喷两次)。氢化可的松醋丙酯，如有必要，用棉绒擦拭头部病变部位。在第0、14、28、42和56天进行全面的临床评估。使用猫皮肤病程度和严重程度指数(FeDESI;图1)点宠主使用带有等级描述符的10厘米视觉模拟量表评估瘙痒。从第14天开始，宠主独立对易用性、耐受性和疗效进行评分，评分范围从1(极差)到5(优秀)。在每次访问时，猫都被称重，并在第0天和第56天收集了4只猫的血液和尿液样本。不可能从其余清醒的猫上收集到足够的样本，因此决定不给猫注射镇静剂进行采样，除非它们的情况需要进一步调查。宠主在每日中记录喷雾次数、不良事件、联合治疗和其他信息。

 

 

The frequency of treatment at days 28 and 42 was reduced to every other day in cats with a >50% reduction in FeDESI score compared with day 0. If the improvement was maintained, the frequency was further reduced to twice weekly. Owners were instructed to increase the frequency of treatment if the skin lesions or pruritus worsened. The cats were withdrawn if they required treatment with a prohibited medication, if there was poor compliance or if they showed unacceptable discomfort. Owners were free to withdraw their animals at any point.

与第0天相比，FeDESI评分下降>50%的猫在第28天和第42天的治疗频率减少到每隔一天。如果改善得到维持，频率进一步减少到每周两次。如果皮肤病变或瘙痒恶化，主人被告知要增加治疗的频率。如果猫咪需要禁用药物治疗，如果依从性差，或者它们表现出不可接受的不适，就会被撤走。主人可以在任何时候自由地撤走他们的动物。

 

Data analysis

数据分析

Intention-to-treat data were analysed. Descriptive statistics were used to describe the demographic data because there was no control group for comparison. The data were tested for normality before analysis (Kolmogorov–Smirnov test; Instat 3 ; Graphpad Inc., San Diego, CA, USA). One-way repeated-measures ANOVAs with Tukey’s post hoc tests (Prism 4 ; Graphpad Inc.) were used to assess the changes in FeDESI and pruritus scores throughout the trial. The FeDESI and pruritus scores for each cat at each time point were correlated using Pearson’s correlation test (Instat 3 ; Graphpad Inc.). Freidman tests with Dunn’s post hoc tests (Prism 4 ; Graphpad Inc.) were used to analyse the owner assessment scores throughout the trial. The proportion of treated cats that achieved >50% reductions in FeDESI or pruritus compared with baseline and that could be maintained on daily, every-other-day or twice-weekly therapy was reported.

分析意向治疗数据。由于没有对照组进行比较，因此使用描述性统计来描述统计数据。分析前对数据进行正态性检验。采用Tukey事后检验的单向重复测量方差分析用于评估整个试验期间FeDESI和瘙痒评分的变化。使用Pearson相关检验对每只猫在每个时间点的FeDESI和瘙痒评分进行相关性分析。friedman测试和Dunn的事后测试用于分析整个试验期间的宠主评估分数。与基线相比，接受治疗的猫的FeDESI或瘙痒症状减少了50%以上，并且可以维持每日、每隔一天或每周两次的治疗。

 

Results

结果

Demographic data

群体数据

Ten cats were enrolled. Eight were domestic short hairs, one was a domestic long hair and one was a British short hair. Six were neutered females and four were neutered males. At entry, the mean age was 6.4 years (SD 3.2 years) and the mean weight was 5.0 kg (SD 1.4 kg).

10只猫被招募。8只家养短毛猫，1只家养长毛猫，1只英国短毛猫。其中6只为已绝育雌性，4只为已去势雄性。入组时平均年龄6.4岁(SD 3.2岁)，平均体重5.0 kg (SD 1.4 kg)。

 

Intention-to-treat analyses

意向处理分析

Three cats were prematurely withdrawn. Two cats were withdrawn at the owner’s request, one at day 28 (perceived poor efficacy) and one at day 42 (because the owner found it difficult to return for re-examinations). One cat required systemic antibiotic treatment for a cat bite abscess and was withdrawn at day 42. On-treatment data were available for all these cats. Intention-to-treat analyses were performed using the last treatment carried forward technique. There were no other significant protocol deviations.

三只猫过早地退出。两只猫在主人的要求下被撤出，一只在第28天(感觉疗效不佳)，另一只在第42天(因为主人发现很难回来重新检查)。一只猫因猫咬伤脓肿需要全身抗生素治疗，并在第42天停药。所有这些猫的治疗数据都是可用的。意向治疗分析采用最后一次治疗结转技术进行。没有其他明显的方案偏差。

 

FeDESI and pruritus scores

FeDESI和瘙痒症评分

The FeDESI (Figure 2) and pruritus scores (Figure 3) significantly decreased throughout the trial (one-way repeated-measures ANOVA, P < 0.0001 in each case). Tukey’s post hoc tests revealed that the day 0 scores were significantly higher than the scores at days 14, 28, 42 and 56 (P < 0.001 in each case). There were no signifi- cant differences between the scores at any of the other time points. The FeDESI and pruritus scores for each cat at each time point were highly correlated (Pearson’s correlation test, P < 0.0001; Figure 4).

在整个试验过程中，FeDESI(图2)和瘙痒评分(图3)显著下降(单因素重复测量方差分析，P < 0.0001)。Tukey的事后检验显示，第0天的得分显著高于第14、28、42和56天的得分(每种情况下P < 0.001)。在任何其他时间点的得分之间没有显著差异。每只猫在每个时间点的FeDESI和瘙痒评分高度相关(Pearson相关检验，P < 0.0001;图4)。

 

At day 56 five of 10 cats had >50% decreases in both FeDESI and pruritus scores compared with day 0. Two cats had >50% decreases in pruritus only, two cats had >50% decreases in FeDESI only, and the remaining cat had <50% decreases in both FeDESI and pruritus scores.

在第56天，与第0天相比，10只猫中有5只的FeDESI和瘙痒评分下降了>50%。两只猫的瘙痒症状下降了>50%，两只猫的FeDESI评分下降了>50%，其余猫的FeDESI和瘙痒症状评分都下降了<50%。

 

Owners’ global evaluation scores

宠主的整体评价分数

The owners’ scores for tolerance (Friedman test, P = 0.003) and ease of administration (P = 0.02)significantly improved during the trial (Figure 5). There was, however, no significant difference in the owners’ scores for efficacy throughout the trial (P = 0.5). Dunn’s  post hoc tests did not reveal any significant differences between any time points for any of the scores.

试验期间，宠主的耐受性评分(Friedman检验，P = 0.003)和给药容易度评分(P = 0.02)显著提高(图5)。然而，在整个试验期间，宠主的疗效评分没有显著差异(P = 0.5)。邓恩的事后测试没有显示任何时间点之间任何分数的显著差异。

 

 

 

 

Figure 1. Feline Extent and Severity Index (FeDESI). Forty-two body sites were scored 0–5 for erythema, excoriation ⁄ erosion and self-induced alopecia, giving a total score ranging from 0 to 630.

图1。猫的范围和严重性指数(FeDESI)。对42个机体部位进行0 - 5分红斑、抓痕/糜烂和自损性脱毛，总分从0分到630分。

 

Frequency of treatment

治疗频率

By day 56, four cats required daily therapy to maintain remission, and six cats could be maintained on every-other-day treatment. Six of the seven cats that completed the whole trial could be maintained on every-other-day therapy. Switching to twice-weekly treatment led to a relapse in clinical signs in all cases.

到第56天，4只猫需要每天治疗来维持缓解，6只猫可以每隔一天治疗一次。完成整个试验的七只猫中，有六只可以每隔一天接受一次治疗。转为每周两次治疗导致所有病例的临床症状复发。

 

Adverse events

不良事件

No adverse events attributable to the trial therapy were reported in any of the cats, and adverse events were not cited as reasons for premature withdrawal from the trial. One cat developed lymphocytic inflammatory bowel disease in the last week of treatment, but this was not thought to be associated with the HCA spray (as the condition was acute, the cat was not observed to ingest the spray after application, and the condition has been managed through diet and intermittent systemic prednisolone with continued HCA treatment). There was no significant change in weight during the trial [day 0, mean 5.0 kg (SD 1.4); day 56, mean 5.0 kg (SD 1.6); one-way repeated-measures ANOVA, P = 0.8]. All the blood and urine parameters were within normal limits in the four sampled cats, and there were no clinically significant changes between days 0 and 56 (data not shown). Four owners reported that their cats (two cats with head and neck dermatitis and two cats with eosinophilic plaque of the ventral abdomen ⁄ medial hindlimbs) would not tolerate the spray, but accepted the HCA solution applied to lesional skin using cotton wool.

在任何猫中均未报告可归因于试验治疗的不良事件，并且不良事件未被引用为过早退出试验的原因。在治疗的最后一周，一只猫出现了淋巴细胞性炎症性肠病，但这被认为与HCA喷雾剂无关(由于病情是急性的，在使用HCA喷雾剂后，没有观察到猫摄入喷雾剂，病情通过饮食和间歇性全身泼尼松龙治疗得到控制)。试验期间体重无显著变化[第0天，平均5.0 kg (SD 1.4);第56天，平均5.0 kg (SD 1.6);单因素重复测量方差分析，P = 0.8]。4只取样猫的所有血液和尿液参数都在正常范围内，并且在第0天至第56天之间没有明显的临床变化(数据未显示)。四位宠主报告说，他们的猫(两只患有头颈部皮肤病的猫和两只患有腹侧/后肢内侧嗜酸性斑块的猫)不能耐受这种喷雾，但接受了用棉球将HCA溶液涂在病变皮肤上。

 

 

Figure 2. Changes in FeDESI score in cats treated with hydrocortisone aceponate spray (means ± SD).

图2。氢化可的松醋丙酯喷雾剂治疗猫的FeDESI评分变化(平均值±SD)。

 

 

Figure 3. Changes in pruritus score (in millimetres) in cats treated with hydrocortisone aceponate spray (means ± SD).

图3。使用氢化可的松醋丙酯喷雾治疗猫瘙痒评分(毫米)的变化(平均值±标准差)。

 

Figure 4. Correlation between the FeDESI score and pruritus score (in millimetres) for each cat at each time point.

图4。每只猫在每个时间点的FeDESI评分与瘙痒评分(单位为毫米)的相关性。

 

 

 

Figure 5. Owners’ scores (median and range) for ease of administration (a), tolerance (b) and efficacy (c) in the cats treated with hydrocortisone aceponate.

图5。患猫宠主在给药(a)、耐受性(b)和有效性(c)方面的评分(中位数和范围)。

 

 

Discussion

讨论

This study shows that a topical 0.0584% HCA spray appears to be a highly effective treatment for cats with presumed allergic dermatitis. There were highly significant improvements in both clinical lesions and pruritus. Five of 10 cats, furthermore, achieved >50% decreases in both FeDESI and pruritus scores by day 56, the point conventionally used to denote a significant clinical improvement. Four more cats achieved >50% reductions in one of these scores. The FeDESI and pruritus scores were highly correlated, suggesting that the HCA spray did not preferentially ameliorate clinical lesions, and that the improvement was probably relevant to the cats’ quality of life. It can, however, be difficult to assess pruritus in cats. The pruritus scale in this study has proved accurate in dogs, but it has not been validated in cats. It is therefore possible that the correlation was due to owners perceiving the improvement in the lesions as evidence of decreased pruritus. These results compare favourably with ciclosporin, where remission in 50–100% of cats has been reported.

本研究表明，一种外用0.0584%的HCA喷雾剂似乎是一种非常有效的治疗猫过敏性皮肤病的方法。临床病变和瘙痒症状均有显著改善。此外，10只猫中有5只在第56天(通常用于表示显着临床改善的点)的FeDESI和瘙痒评分均下降了>50%。另外四只猫在其中一项得分上降低了50%以上。FeDESI和瘙痒评分高度相关，表明HCA喷雾剂并没有优先改善临床病变，这种改善可能与猫的生活质量有关。然而，评估猫的瘙痒是很困难的。这项研究中的瘙痒量表在犬上被证明是准确的，但在猫上还没有得到验证。因此，这种相关性可能是由于宠主认为病变的改善是瘙痒减少的证据。这些结果与环孢素相比是有利的，据报道，环孢素在50-100%的猫中得到缓解。

 

The owners’ global evaluation scores corroborated the clinical scores. There was significant improvement in ease of administration and tolerance throughout the trial, suggesting that the owners and their cats found treatment easier with experience. In some cases, this was achieved by indirectly applying the HCA solution using cotton wool, although this method makes it difficult to determine the dose applied. There was no significant change in the efficacy score, but the majority of owners rated the efficacy as good or excellent at each time point.

宠主的整体评估得分证实了临床得分。在整个试验过程中，治疗的容易程度和耐受性都有了显著的改善，这表明猫的主人和他们的猫发现治疗变得更容易了。在某些病例中，这是通过使用棉球间接施用HCA溶液实现的，但这种方法难以确定所施用的剂量。疗效评分无明显变化，但大多数宠主在每个时间点都将疗效评为良好或优秀。

 

The response to treatment was rapid, with most of the clinical improvement evident by day 14. Clinical scores tended to improve thereafter in most cats, but there were no significant differences from day 14 to 56. Individual lesion scores showed that eight of 10 cats were effectively in remission by day 28 (data not shown). This response appears to be similar to that in canine AD, where most dogs are improved by 14 days but full remission usually takes 28 days.  The response times to the HCA spray in presumed feline allergic dermatitis also appear to be similar to those following treatment with ciclosporin, where clinical improvement is evident in most cats by 10–28 days but full remission takes 30–90 days. The longer response times appear to be associated with eosinophilic granuloma and indolent ulcers.

治疗反应迅速，大多数临床改善在第14天明显。此后大多数猫的临床评分趋于改善，但从第14天到第56天没有显著差异。个体病变评分显示，10只猫中有8只在第28天有效缓解(数据未显示)。这种反应似乎与犬AD相似，大多数犬在14天内得到改善，但完全缓解通常需要28天。在推测的猫过敏性皮肤病中，使用HCA喷雾的反应时间似乎与使用环孢素治疗的反应时间相似，其中大多数猫的临床改善在10-28天内明显，但完全缓解需要30-90天。较长的反应时间似乎与嗜酸性肉芽肿和无痛性溃疡有关。

 

It was possible to reduce the frequency of treatment with HCA to every other day in most cats. It was not, however, possible to reduce the frequency further to twice weekly. This is in contrast to canine AD, where seven of 21 dogs21 and 10 of 24 dogs22 could be maintained on twice-weekly therapy in two trials. Variation in the frequency of long-term medication may be due to the inherent severity of condition, environment (e.g. allergen or irritant exposure) and ⁄ or genotypic differences in response to drug therapy or compliance. Coat length did not affect treatment outcome in dogs,  although the denser coat in cats may limit penetration of HCA to the skin. This would not be expected early in treatment when most affected skin will be alopecic, but may affect the dose and ⁄ or frequency required to maintain remission once the coat regrows. It is also possible that additional therapy, such as essential fatty acids, antihistamines, allergen avoidance and allergen-specific immunotherapy, would permit less frequent treatment in cats.

对大多数猫来说，用HCA治疗的频率可以减少到每隔一天。然而，不可能将频率进一步减少到每周两次。这与犬AD形成对比，在两次试验中，21只犬中的7只(21)和24只犬中的10只(22)每周接受两次治疗。长期用药频率的变化可能是由于固有的病情严重程度、环境(如过敏原或刺激物暴露)和对药物治疗反应或依从性的基因型差异。犬的被毛长度不影响治疗结果， 但的被毛较密可能会限制HCA对皮肤的渗透。这在治疗早期是不可能的，因为大多数患病皮肤会脱毛，但可能会影响到一旦被毛再生后维持缓解所需的剂量和/或频率。还有一种可能是，额外的治疗，如必需脂肪酸、抗组胺药、避免过敏原和过敏原特异性免疫治疗，可以减少猫的治疗频率。

 

The HCA treatment was well tolerated, with no adverse events attributable to the spray. No significant changes were seen in blood and urine parameters, although only four cats could be sampled. The remaining cats would have required sedation, and it was decided that this would only be performed if the cats’ condition gave cause for concern. Four cats would not tolerate the spray, although HCA could be applied indirectly using cotton wool. The results of this trial indicate that HCA spray has a better benefit:risk profile than other anti-inflammatory agents, such as antihistamines, glucocorticoids and ciclosporin.  This study, however, only followed 10 cats for a maximum of 56 days, and larger and longer term studies of safety are warranted.

HCA治疗耐受性良好，没有可归因于喷雾剂的不良事件。血液和尿液参数没有明显变化，但只有四只猫可以取样。剩下的猫将需要镇静，并且决定只有在猫的疾病引起关注时才会进行镇静。有四只猫不能忍受这种喷雾，但HCA可以用棉球间接喷洒。本试验结果表明，HCA喷雾比其他抗炎剂(如抗组胺药、糖皮质激素和环孢素)具有更好的益处:风险特征。然而，这项研究只对10只猫进行了最多56天的跟踪研究，更大规模、更长期的安全性研究是有必要的。

 

Where possible, this study used reported and validated outcome measures. The CADESI-03 is a relevant and reliable assessment of clinical severity in canine AD, and the system has been used as a basis for assessing skin lesions in cats.  The FeDESI26 used in this study has good intra- and interobserver reliability across a number of presentations, including eosinophilic plaque, symmetrical alopecia, miliary dermatitis, and head and neck dermatitis, although it only provides an indirect assessment of pruritus through excoriation. Direct pruritus scores have not been validated for cats, although the visual analog scale with behavioural descriptors used in this study has been found to be accurate in dogs. Nevertheless, while validated lesion and pruritus scores are useful for evaluating and comparing treatment, it is likely that quality of life is more important to owners and their cats. It has been difficult to assess quality of life reliably, and studies have often reported global evaluation scores. These, however, can be misleading; for example, in an earlier trial of the HCA spray, some owners found that the global score contradictory because they found the spray efficacious but difficult to apply. In this study, therefore, the owners’ evaluation was divided into efficacy, ease of application and tolerance. Very recently, quality-of-life questionnaires have been developed and validated for dogs.  Similar questionnaires validated for cats could prove useful in future studies.

在可能的情况下，本研究使用了报告和验证的结果测量。CADESI-03是犬AD临床严重程度的相关可靠评估，该系统已被用作评估猫皮肤病变的基础。本研究中使用的FeDESI在许多表现中具有良好的观察者内部和观察者之间的可靠性，包括嗜酸性斑块、对称性脱毛、粟粒性皮炎和头颈部皮肤病，但它只能通过抓痕间接评估瘙痒。虽然本研究中使用的带有行为描述符的视觉模拟量表在犬上是准确的，但直接瘙痒评分尚未在猫上得到验证。然而，虽然经过验证的病变和瘙痒评分对于评估和比较治疗是有用的，但对于主人和他们的猫来说，生活质量可能更重要。可靠地评估生活质量一直很困难，研究经常报告整体评估分数。然而，这些可能具有误导性;例如，在HCA喷雾的早期试验中，一些宠主发现整体得分矛盾，因为他们发现喷雾有效但难以使用。因此，在本研究中，宠主的评价分为功效、使用方便度和耐受性。最近，人们为犬开发并验证了生活质量调查问卷。对猫进行的类似问卷调查可能在未来的研究中有用。

 

This study was carried out to good clinical practice standards. Rigorous inclusion and exclusion criteria were established before the trial to ensure, as far as possible, a diagnosis of feline allergic skin disease. The diagnosis, however, can be challenging. In particular, it was difficult to carry out the food trials because most cats refused the trial food before completing the 8 week trial. It is therefore possible that some of the cats had cutaneous adverse food reactions. Selection bias in breed, age, sex, weight and clinical severity was not apparent. Detection bias by the investigator and owners was, however, likely because this was an open label study. Performance bias was considered unlikely because there were no concomitant treatments apart from flea control. Attrition bias was present, with three cats withdrawn, although on-treatment data permitting intention-to-treat analysis were available for all 10 cats. It is possible that this biased towards a favourable response to treatment, although poor efficacy was cited as a reason for withdrawal in only one case.

这项研究是按照良好的临床实践标准进行的。试验前制定了严格的纳入和排除标准，以尽可能确保猫过敏性皮肤病的诊断。然而，诊断可能是具有挑战性的。特别是，由于大多数猫在完成8周的试验之前就拒绝了试验食物，因此很难进行食物试验。因此，有些猫可能有皮肤上的食物不良反应。品种、年龄、性别、体重和临床严重程度的选择偏倚不明显。然而，研究者和宠主可能存在检测偏差，因为这是一项标签外研究。表现偏差被认为不太可能，因为除了跳蚤控制之外没有伴随治疗。尽管对所有10只猫进行了意向治疗分析，但仍存在消耗偏差，有3只猫退出了治疗。这可能偏向于对治疗的有利反应，但只有一个病例的疗效差被引用为停药的原因。

 

In conclusion, this study demonstrated that a 0.0584% HCA spray was efficacious and well tolerated in 10 cats with presumed allergic skin disease. It is not, however, licensed for use in cats. This was, furthermore, a small, open label pilot study, and these findings should be confirmed in larger, longer term, blinded RCTs.

总之，本研究表明，0.0584%的HCA喷雾对10只假定患有过敏性皮肤病的猫有效且耐受性良好。然而，它没有被许可用于猫上。此外，这是一项小型、标签外的先导研究，这些发现应该在更大、更长期、盲法随机对照试验中得到证实。