oclacitinib and Dermatitis--Atopic

Oclacitinib was approved in the United States 10 years ago for the management of atopic dermatitis (AD) and allergic skin disease in dogs. Many studies and case reports have been published in the past 10 years on the efficacy and safety of this medication, both at labeled doses to treat allergic dogs and off label to treat other diseases and given to other species. Concerns and confusion have occurred for both clinicians and owners regarding the long-term safety of this drug. The purpose of this review is to present the current knowledge on the efficacy, speed of action, effects on the immune system, and clinical safety of oclacitinib, based on evidence and published literature. We also aim to summarize the lessons learned in the past 10 years and to propose directions for the future.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Pyrimidines

New molecularly targeted therapeutics are changing dermatologic therapy. Janus kinase-signal transducer and activator of transcription (JAK-STAT) is an intracellular signaling pathway upon which many different proinflammatory signaling pathways converge. Numerous inflammatory dermatoses are driven by soluble inflammatory mediators, which rely on JAK-STAT signaling, and inhibition of this pathway using JAK inhibitors might be a useful therapeutic strategy for these diseases. Growing evidence suggests that JAK inhibitors are efficacious in atopic dermatitis, alopecia areata, psoriasis, and vitiligo. Additional evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions. JAK inhibitors can be administered orally or used topically and represent a promising new class of medications. The use of JAK inhibitors in dermatology is reviewed here.

Topics: Alopecia Areata; Anti-Inflammatory Agents; Azetidines; Clinical Trials as Topic; Dermatitis, Atopic; Dermatologic Agents; Humans; Janus Kinases; Molecular Targeted Therapy; Nitriles; Piperidines; Protein Kinase Inhibitors; Psoriasis; Purines; Pyrazoles; Pyrimidines; Pyrroles; Signal Transduction; Skin Diseases; Sulfonamides; Vitiligo

Canine atopic dermatitis is a common skin disease seen in veterinary clinical practice. Several factors appear to contribute to the cutaneous inflammation and pruritus. The therapeutic strategy should focus on control of those factors that can be identified and for which interventional measures are feasible; these include ectoparasites, bacterial/fungal infection and dietary hypersensitivity. Ectoparasites, particularly fleas, are not the cause of atopic dermatitis, but they are a confounding factor, which can exacerbate pruritus, and preventative measures are therefore indicated. Bacterial and yeast infections are frequently associated with atopic dermatitis and initial systemic and/or topical therapy should be considered, followed by regular topical treatment for preventing relapse. Concurrent dietary hypersensitivity should be investigated by undertaking an elimination/provocation trial, followed by feeding of a hypoallergenic diet where appropriate. Depending on the severity of the clinical signs of atopic dermatitis and the willingness and expectations of owners, symptomatic treatment and/or specific interventional therapy for environmental allergy (allergen avoidance, allergen-specific immunotherapy) may be implemented. Symptomatic treatment includes use of glucocorticoids (systemically or topically), ciclosporin and oclacitinib. Other treatment modalities of lower or less proven efficacy include antihistamines, dextromethorphan, fatty acids, feline interferon-omega, misoprostol, pentoxifylline, specific serotonin re-uptake inhibitors and tricyclic antidepressant drugs. The therapeutic approach should be reviewed at regular intervals and tailored to the individual's needs. A successful long-term outcome can usually be achieved by combining the various treatment approaches in a way that maximises their benefits and minimises their drawbacks.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Glucocorticoids; Pyrimidines; Sulfonamides

A rebound of pruritus occasionally occurs after oclacitinib dose reduction in dogs with atopic dermatitis (AD).. To determine whether an initial 4-day course of prednisolone decreases the probability of a pruritus rebound after reducing the frequency of oclacitinib administration.. Forty dogs with mild-to-moderate AD lesions and moderate-to-severe pruritus.. Dogs were randomised to receive oclacitinib at 0.4-0.6 mg/kg twice daily for 14 days then once daily, alone or with prednisolone at 0.5 mg/kg, orally, twice daily for the first 4 days. Clinicians graded the Canine Atopic Dermatitis Extent and Severity Index (CADESI)4 and 2D-investigator global assessment (IGA) before and after 28 days; owners assessed the pruritis Visual Analog Scale (PVAS)10 and Owner Global Assessment of Treatment Efficacy (OGATE) on Day (D)0, D4, D14, D21 and D28. We considered a rebound any increase greater than one PVAS10 grade at D21 compared to D14.. On D21, there were significantly fewer rebounds in the dogs receiving prednisolone (three of 20, 15%) compared to those given oclacitinib alone (nine of 20, 45%; Fisher's test, p = 0.041). Compared to oclacitinib monotherapy, the concurrent administration of prednisolone for the first 4 days led to significantly lower PVAS10 on D4 and D28, CADESI4 and 2D-IGA on D28, and OGATE on D21 and D28 (Wilcoxon-Mann-Whitney U-tests). Adverse effects of therapy were minor, intermittent and self-resolving.. The initial addition of 4 days of prednisolone significantly decreased the probability of a rebound of pruritus 1 week after oclacitinib dose reduction. This short concomitant glucocorticoid administration led to a higher skin lesion improvement and improved perception of treatment efficacy with minimal adverse effects.. Un rebond du prurit se produit occasionnellement après une réduction de la dose d'oclacitinib chez les chiens atteints de dermatite atopique (DA).. Déterminer si une cure initiale de quatre jours de prednisolone diminue la probabilité d'un rebond de prurit après réduction de la fréquence d'administration d'oclacitinib.. Quarante chiens présentant des lésions de DA légères à modérées et un prurit modéré à sévère. MATÉRIELS ET MÉTHODES: Des chiens ont été randomisés pour recevoir de l'oclacitinib à raison de 0,4 à 0,6 mg/kg deux fois par jour pendant 14 jours puis une fois par jour, seul ou avec de la prednisolone à 0,5 mg/kg, par voie orale, deux fois par jour pendant les quatre premiers jours. Les cliniciens ont évalué l'indice d'étendue et de gravité de la dermatite atopique canine (CADESI)4 et l'évaluation globale de l'investigateur 2D (IGA) avant et après 28 jours ; les propriétaires ont évalué l'échelle visuelle analogique du prurit (PVAS)10 et l'évaluation globale de l'efficacité du traitement par le propriétaire (OGATE) aux jours (J)0, J4, J14, J21 et J28. Nous avons considéré comme un rebond toute augmentation supérieure à un grade PVAS10 à J21 par rapport à J14. RÉSULTATS: A J21, il y a eu significativement moins de rebonds chez les chiens ayant reçu de la prednisolone (trois sur 20, 15%) par rapport à ceux ayant reçu de l'oclacitinib seul (neuf sur 20, 45%) (test de Fisher, p = 0,041). Par rapport à l'oclacitinib en monothérapie, l'administration concomitante de prednisolone pendant les quatre premiers jours a entraîné une baisse significative de PVAS10 à J4 et J28, CADESI4 et 2D-IGA à J28, et OGATE à J21 et J28 (tests U de Wilcoxon-Mann-Whitney). Les effets indésirables du traitement étaient mineurs, intermittents et résolutifs.. L'ajout initial de quatre jours de prednisolone a significativement diminué la probabilité d'un rebond du prurit une semaine après la réduction de la dose d'oclacitinib. Cette courte administration concomitante de glucocorticoïdes a entraîné une amélioration plus importante des lésions cutanées et une meilleure perception de l'efficacité du traitement avec un minimum d'effets indésirables.. INTRODUCCIÓN: ocasionalmente se produce una recidiva del prurito después de la reducción de la dosis de oclacitinib en perros con dermatitis atópica (AD).. Determinar si un curso inicial de cuatro días de prednisolona disminuye la probabilidad de una recidiva del prurito después de reducir la frecuencia de administración de oclacitinib.. Cuarenta perros con lesiones de AD de leves a moderadas y prurito de moderado a severo. MATERIALES Y MÉTODOS: los perros se distribuyeron al azar para recibir oclacitinib a 0,4-0,6 mg/kg dos veces al día durante 14 días, luego una vez al día, solo o con prednisolona a 0,5 mg/kg, por vía oral, dos veces al día durante los primeros cuatro días. Los veterinarios calificaron el índice de extensión y severidad de la dermatitis atópica canina (CADESI)4 y la evaluación global 2D del investigador (IGA) antes y después de 28 días; los propietarios evaluaron la escala análoga visual de prurito (PVAS)10 y la evaluación global del propietario de la eficacia del tratamiento (OGATE) en el día (D)0, D4, D14, D21 y D28. Consideramos una recidiva cualquier aumento superior a un grado PVAS10 en D21 en comparación con D14.. En el D21, hubo significativamente menos recidivas en los perros que recibieron prednisolona (tres de 20, 15 %) en comparación con los que recibieron oclacitinib solo (nueve de 20, 45 %) (prueba de Fisher, p = 0,041). En comparación con la monoterapia con oclacitinib, la administración concomitante de prednisolona durante los primeros cuatro días condujo a una PVAS10 significativamente más baja en D4 y D28, CADESI4 y 2D-IGA en D28, y OGATE en D21 y D28 (prueba U de Wilcoxon-Mann-Whitney). Los efectos adversos de la terapia fueron menores, intermitentes y de resolución automática. CONCLUSIONES Y RELEVANCIA CLÍNICA: La adición inicial de cuatro días de prednisolona disminuyó significativamente la probabilidad de una recidiva de prurito una semana después de la reducción de la dosis de oclacitinib. Esta breve administración concomitante de glucocorticoides condujo a una mejoría de las lesiones cutáneas y también mejoró la percepción de la eficacia del tratamiento con efectos adversos mínimos.. Gelegentlich kommt es bei Hunden mit atopischer Dermatitis (AD) nach der Reduktion von Oclacitinib zu einem Rebound des Pruritus.. Das Ziel war es festzustellen, ob eine vier tägige Initialbehandlung mit Prednisolon die Wahrscheinlichkeit eines Rebounds des Pruritus bei Reduzierung der Frequenz der Oclacitinib Verabreichung vermindern würde.. Vierzig Hunde mit mild bis moderaten AD-Läsionen und moderat bis hochgradigem Pruritus.. Die Hunde wurden zufällig in Gruppen eingeteilt, um Oclacitinib bei einer Dosierung von 0,4-0,6 mg/kg zunächst zweimal täglich 14 Tage lang, dann einmal täglich zu erhalten; allein oder mit Prednisolon bei einer Dosis von 0,5 mg/kg, per os, zweimal täglich für die ersten vier Tage. KlinikerInnen bewerteten mittels Canine Atopic Dermatitis Extent und Severity Index (CADESI)4 und 2D-Investigator Global Assessment (IGA) vor und nach 28 Tagen; die BesitzerInnen beurteilten den Juckreiz mittels Visual Analog Scale (PVAS)10 und Owner Global Assessment of Treatment Efficacy (OGATE) am Tag (D)0, D4, D14, D21 und D28. Als Rebound wurde jede Zunahme bewertet, die größer war als ein PVAS10 Grad am D21 im Vergleich zu D14.. Am D21 bestanden signifikant weniger Rebounds bei den Hunden, die Prednisolon (drei von 20; 15%) erhielten im Vergleich zu jenen, die Oclacitinib alleine (neun von 20; 45%) (Fisher´s Test, p = 0,041) bekamen. Im Vergleich zu Oclacitinib Monotherapie führt die gleichzeitige Verabreichung von Prednisolon für die ersten vier Tage zu signifikant niedrigeren PVAS10 Werten am D4 und D28, CADESI4 und 2D-IGA am D28, und OGATE am D21 und D28 (Wilcoxon-Mann-Whitney U-Tests). Nebenwirkungen waren gering, vorübergehend und verschwanden von selbst.. Die anfängliche Zugabe von Prednisolon für vier Tage reduzierte die Wahrscheinlichkeit eines Pruritus Rebounds eine Woche nach Dosisreduzierung des Oclacitinib signifikant. Diese kurze gleichzeitige Glukokortikoid Verabreichung führte zu einer rascheren Verbesserung der Hautveränderungen und verbesserte die Wahrnehmung der Behandlungseffizienz mit minimalen Nebenwirkungen.. 背景: アトピー性皮膚炎(AD)の犬において、オクラシチニブ減量後に掻痒のリバウンドが生じることがある。 目的: 本研究の目的は、オクラシチニブの投与頻度を減らした後、プレドニゾロンの4日間投与により、掻痒のリバウンドが生じる確率が減少するかどうかを検討することであった。 対象動物: 軽度から中等度のAD病変を有し、中等度から重度の掻痒を有する犬40頭。 材料と方法: 対象犬を、オクラシチニブ0.4~0.6mg/kgを1日2回14日間投与後、オクラシチニブ1日1回単独で、またはプレドニゾロン0.5mg/kgを1日2回、最初の4日間経口投与する方法のどちらかに無作為に分けた。臨床医は28日前後に犬アトピー性皮膚炎の程度および重症度指数(CADESI)4および2D-調査者グローバル評価(IGA)を評価し、飼い主は0日(D0)、D4、D14、D21およびD28に痒みの視覚的アナログスケール(PVAS10)および治療効果に関するグローバル評価(OGATE)を評価した。D14と比較してD21でPVAS10が1段階以上上昇した場合、リバウンドとした。 結果: D21において、プレドニゾロン投与群(20頭中3頭、15%)では、オクラシチニブ単独投与群(20頭中9頭、45%)と比較してリバウンドが有意に少なかった(Fisher's test、p=0.041)。オクラシチニブ単剤療法と比較して、最初の4日間のプレドニゾロン同時投与により、D4およびD28のPVAS10、D28のCADESI4および2D-IGA、D21およびD28のOGATEが有意に低下した(Wilcoxon-Mann-Whitney U-tests)。治療による有害事象は軽微で、断続的であり、自己回復的であった。 結論と臨床的意義: 最初の4日間のプレドニゾロン加療により、オクラシチニブ減量1週間後の痒みのリバウンドの発生率が有意に減少した。この短期間のグルココルチコイド併用投与により、皮膚病変の改善度が高く、有害事象も少なく治療効果の認存も改善された。.. 背景: 患有特应性皮炎 (AD) 的犬在降低奥拉替尼剂量后，偶尔会出现瘙痒反弹。 目的: 确定泼尼松龙初始4天疗程是否可降低奥拉替尼给药频率后瘙痒反弹的概率。 动物: 40只患有轻度至中度 AD 病变和中度至重度瘙痒的犬。 材料和方法: 犬随机接受奥拉替尼0.4-0.6 mg/kg每日两次给药14天，单独给药，或者前4天同时泼尼松龙0.5 mg/kg每日两次经口给药。临床医生在28天之前和之后对犬特应性皮炎程度和严重指数 (CADESI)4 和 2D 研究者整体评估 (IGA) 进行分级；犬主人在第 (D)0、D4、D14、D21和 D28 天评估瘙痒视觉模拟量表 (PVAS)10 和犬主人治疗有效性整体评估 (OGATE)。我们认为与 D14 相比，D21时 PVAS10 等级的任何反弹增加均大于1级。 结果: 在D21，接受泼尼松龙的犬反弹 (3/20，15%) 显著少于接受奥拉替尼单药的犬 (9/20，45%)(Fisher检验，p = 0.041)。与奥拉替尼单药治疗相比，在前4天同时给予泼尼松龙导致 D4 和 D28 时PVAS10、D28时 CADESI4 和 2D-IGA 以及 D21 和 D28 时 OGATE 显著降低(Wilcoxon-Mann-Whitney U检验)。治疗的不良反应为轻微、间歇发生和可自愈。 结论和临床相关性: 初始加用4天泼尼松龙显著降低了奥拉替尼减量后1周瘙痒反弹的概率。这种短期伴随糖皮质激素给药导致更有好的皮肤病变改善，以及更显著地感知治疗疗效，不良反应极小。.. Após a redução da dose de oclacitinb, ocasionalmente ocorre um efeito rebote de prurido nos cães com dermatite atópica (DA).. Determinar se um curso inicial de quatro dias de prednisolona é capaz de reduzir a probabilidade de um efeito rebote de prurido após reduzir a frequência de administração de oclacitinib.. Quarenta cães com lesões leves a moderadas de DA e prurido moderado a intenso. MATERIAIS E MÉTODOS: Os cães foram divididos aleatoriamente para receber oclacitinib na dose de 0,4-0,6 mg/kg duas vezes ao dia por 14 dias e depois uma vez ao dia, isoladamente ou associado à prednisolona na dose de 0,5 mg/kg, por via oral, duas vezes ao dia nos primeiros quatro dias. Os clínicos utilizaram o Índice de Extensão e Gravidade da Dermatite Atópica Canina (CADESI)4 e a avaliação global do investigador 2D (IGA) antes e após 28 dias; os proprietários utilizaram a Escala Visual Analógica de Prurido (PVAS)10 para avaliar o prurido e a Avaliação Global da Eficácia do Tratamento pelo Proprietário (OGATE) no Dia (D)0, D4, D14, D21 e D28. Consideramos um rebote qualquer aumento maior que um grau no PVAS10 no D21 comparado ao D14.. No D21, houve significativamente menos rebotes nos cães que receberam prednisolona (três de 20, 15%) em comparação com aqueles que receberam oclacitinib isoladamente (nove de 20, 45%) (teste de Fisher, p = 0,041). Em comparação à monoterapia com oclacitinib, a administração concomitante de prednisolona nos primeiros quatro dias levou à redução significativa de PVAS10 em D4 e D28, CADESI4 e 2D-IGA em D28 e OGATE em D21 e D28 (testes U de Wilcoxon-Mann-Whitney). Os efeitos adversos da terapia foram mínimos, intermitentes e auto-limitantes. CONCLUSÕES E RELEVÂNCIA CLÍNICA: A inclusão inicial de quatro dias de prednisolona diminuiu significativamente a probabilidade de rebote do prurido uma semana após a redução da dose de oclacitinib. Esta curta administração concomitante de glicocorticoides levou a uma melhor resposta na redução das lesões cutâneas e melhor percepção da eficácia do tratamento com efeitos adversos mínimos.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Immunoglobulin A; Prednisolone; Pruritus

Canine atopic dermatitis (AD) is associated with increased levels of allergen-specific IgE due to hyper-sensitization to environmental allergens. Intradermal testing (IDT) and allergen-specific IgE serology testing are often used to determine the allergens which elicit an IgE response in animals with a diagnosis of AD. The objective of this study was to determine the effects of oclacitinib on IDT and allergen-specific IgE serology testing using a laboratory model of house-dust mite sensitized Beagle dogs. Twenty-four (24) normal, healthy purpose-bred Beagle dogs were sensitized to house dust mites (HDM, Dermatophagoides farinae) and randomly assigned to placebo-, oclacitinib- (0.4 mg/kg/dose PO), or prednisolone-treated (0.5 mg/kg/dose PO) groups. After 14 days of twice daily dosing, the effects of prednisolone and oclacitinib were compared to placebo using baseline and post-dose IDT and allergen-specific IgE serum measurements. Sensitized dogs had increased circulating HDM-specific IgE for at least two weeks post-sensitization. Prednisolone significantly inhibited the measurable sensitivity of IDT, while oclacitinib did not. Neither prednisolone nor oclacitinib imposed significant effects on allergen-specific IgE serum levels, suggesting oclacitinib may have potential to be used in dogs concurrently undergoing intradermal skin testing and/or allergen-specific IgE serology testing without interference with test results.

Topics: Allergens; Animals; Antigens, Dermatophagoides; Dermatitis, Atopic; Dermatophagoides farinae; Dog Diseases; Dogs; Immunoglobulin E; Prednisolone; Pyroglyphidae

Polyunsaturated fatty acids (PUFA) can be beneficial in the management of canine atopic dermatitis (cAD). A commercial product PCSO-524 containing PUFA has demonstrated anti-inflammatory effects in dogs.. To evaluate the efficacy of PCSO-524, in combination with oclacitinib in dogs with cAD.. Seventeen client-owned dogs with cAD.. A randomised, double-blinded, controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg) twice a day for 14 days, then once a day until Day (D)42. They were randomly divided into two groups: PCSO-524 (n = 9) and sunflower oil (n = 8). Clinical status was assessed by Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) and pruritus Visual Analog Scale (pVAS) at baseline (D0), D14, D28 and D42. Trans epidermal water loss (TEWL) was measured at the same time points.. CADESI scores decreased significantly after treatment and there was a significant difference between the PCSO-524 and the control group at D28 (p = 0.04) and D42 (p = 0.03). The PCSO-524 group also demonstrated a significantly decreased pVAS on D28 and D42 (p < 0.001 and p < 0.001) compared to D0, while significant differences were observed in the control group at D14 and D28 (p < 0.01 and p = 0.04) and not at D42 (p = 0.12). The mean TEWL showed a significant decrease at D28 and D42 in the PCSO-524 group, compared to the control group (p = 0.002 and p < 0.001).. The combination of PCSO-524 and oclacitinib may help to alleviate the rebound effect that occurs when tapering down the dosage of oclacitinib, as compared to using oclacitinib alone for the management of cAD.. 背景: 多不饱和脂肪酸(PUFA)可用于治疗犬特应性皮炎(cAD)。含有PUFA的商业产品PCSO-524已在犬身上显示出抗炎作用。 假设/目的: 评估PCSO-524联合奥拉替尼治疗犬cAD的疗效。 动物: 17只客户饲养的cAD患犬。 材料和方法: 一项随机、双盲、对照试验。所有犬均接受奥拉替尼(0.4-0.6 mg/kg，每天两次，持续14天，然后每天一次，直到第42天(D)。他们被随机分为两组。PCSO-524(n=9)和向日葵油(n=8)。在基线(D0)、D14、D28和D42时，通过犬特应性皮炎程度和严重程度指数、第4次迭代(CADESI-04)和瘙痒视觉模拟量表(pVAS)评估临床状态。在相同的时间点测量经表皮水分流失(TEWL)。 结果: 治疗后CADESI评分显著下降，PCSO-524组与对照组在D28(p=0.04)和D42(p=0.03)时有显著差异，而对照组在D14和D28时观察到显著差异(p<0.01和p=0.04)，而在D42时没有(p=0.12)。与对照组相比，PCSO-524组在D28和D42时的平均TEWL显著降低(p=0.002和p<0.001)。 结论和临床相关性: 与单独使用奥拉替尼治疗cAD相比，PCSO-524和奥拉替尼的联合用药可能有助于缓解减少奥拉替尼剂量时出现的反弹效应。.. Les acides gras polyinsaturés (AGPI) peuvent être bénéfiques dans le traitement de la dermatite atopique canine (DAC). Un produit commercial, le PCSO-524, contenant des AGPI, démontre des effets anti-inflammatoires chez les chiens. HYPOTHÈSE/OBJECTIFS: Évaluer l'efficacité du PCSO-524, en association avec l'oclacitinib, chez les chiens atteints de DAC.. Dix-sept chiens appartenant à des clients et souffrant de DAC. MATÉRIELS ET MÉTHODES: Essai contrôlé, randomisé, en double aveugle. Tous les chiens sont traités avec de l'oclacitinib (0,4-0,6 mg/kg deux fois par jour pendant 14 jours, puis une fois par jour jusqu'au jour (J)42. Ils sont répartis aléatoirement en deux groupes. PCSO-524 (n = 9) et huile de tournesol (n = 8). Le score clinique est évalué par le « Canine Atopic Dermatitis Extent and Severity Index, 4éme édition» (CADESI-04) et par l'échelle visuelle analogique du prurit (pVAS) au début de l'étude (J0), à J14, à J28 et à J42. La perte d'eau transépidermique (TEWL) est mesurée aux mêmes moments. RÉSULTATS: Les scores CADESI diminuent de manière significative après le traitement et il y a une différence significative entre le groupe PCSO-524 et le groupe témoin à J28 (p = 0,04) et J42 (p = 0,03). Le groupe PCSO-524 montre également une diminution significative du pVAS à J28 et J42 (p < 0,001 et p < 0,001) par rapport à J0, alors que des différences significatives sont observées dans le groupe témoin à J14 et J28 (p < 0,01 et p = 0,04), mais pas à J42 (p = 0,12). Le TEWL moyen diminue significativement à J28 et J42 dans le groupe PCSO-524, par rapport au groupe témoin (p = 0,002 et p < 0,001).. L'association de PCSO-524 et d'oclacitinib peut contribuer à atténuer l'effet rebond qui se produit lors de la réduction progressive de la dose d'oclacitinib, par rapport à l'utilisation de l'oclacitinib seul pour la prise en charge de la DAC.. 背景: 多価不飽和脂肪酸(PUFA)は犬アトピー性皮膚炎(cAD)の管理に有益である。PUFAを含む市販製品PCSO-524は、犬において抗炎症効果を示した。 仮説/目的: 本研究の目的は、PCSO-524およびオクラシチニブの併用によるcADに対する有効性を評価することであった。 対象動物: cADを有するオーナー所有犬17頭。 材料と方法: 無作為化二重盲検比較試験を実施した。すべての犬にオクラシチニブ(0.4~0.6mg/kgを1日2回、14日間投与し、その後1日1回、42日目まで投与)を投与した。無作為にPCSO-524(n=9)投与群およびヒマワリ油(n=8)投与群の2群に分けられた。臨床状態は、試験開始0日目、14日目、28日目および42日目において、Canine Atopic Dermatitis Extent and Severity Index, 4th iteration(CADESI-04)および痒みのVisual Analog Scale(pVAS)で評価した。経皮水分蒸散量(TEWL)も同じ時点で測定した。 結果: CADESIスコアは治療後に有意に減少し、28日目(p = 0.04)および42日目(p = 0.03)においてPCSO-524群および対照群間に有意差が認められた。PCSO-524群はまた、試験開始日と比較して28日目および42日目でpVASの有意な減少を示したが(p<0.001とp<0.001)、対照群では14日目および28日目で有意差が観察された(p<0.01とp=0.04)が、42日目では観察されなかった(p=0.12)。平均TEWLは、PCSO-524群で28日目および42日目において、対照群と比較して有意な減少を示した(p = 0.002およびp < 0.001)。 結論と臨床的意義: PCSO-524およびオクラシチニブの併用は、cADの管理にオクラシチニブ単独使用した場合と比較して、オクラシチニブの用量を漸減する際に生じるリバウンド効果を軽減するのに役立つ可能性がある。.. Os ácidos graxos poliinsaturados (PUFA) podem ser benéficos no tratamento da dermatite atópica canina (DAC). Um produto comercial PCSO-524 contendo PUFA demonstrou efeito anti-inflamatório em cães. HIPÓTESE/OBJETIVOS: Avaliar a eficácia do PCSO-524, em combinação com oclacitinib, em cães com DAC.. Dezessete cães de clientes com DAC. MATERIAIS E MÉTODOS: Um estudo randomizado, duplo-cego e controlado. Todos os cães foram tratados com oclacitinib (0,4-0,6 mg/kg duas vezes ao dia por 14 dias, depois uma vez ao dia até o Dia (D)42. Eles foram divididos aleatoriamente em dois grupos. PCSO-524 (n = 9) e óleo de girassol (n = 8). A avaliação clínica foi feita utilizando o Índice de Extensão e Gravidade da Dermatite Atópica Canina, 4ª iteração (CADESI-04) e Escala Visual Analógica de prurido (pVAS) no tempo zero (D0), D14, D28 e D42. Mensurou-se a perda de água transepidérmica (TEWL) nos mesmos pontos de tempo.. Os escores CADESI diminuíram significativamente após o tratamento e houve uma diferença significativa entre o PCSO-524 e o grupo controle em D28 (p = 0,04) e D42 (p = 0,03). O grupo PCSO-524 também demonstrou uma pVAS significativamente diminuída em D28 e D42 (p < 0,001 e p < 0,001) em comparação com D0, enquanto diferenças significativas foram observadas no grupo controle em D14 e D28 (p < 0,01 e p = 0,04) , e não em D42 (p = 0,12). A média TEWL apresentou uma diminuição significativa em D28 e D42 no grupo PCSO-524, em comparação com o grupo controle (p = 0,002 e p < 0,001). CONCLUSÕES E RELEVÂNCIA CLÍNICA: A combinação de PCSO-524 e oclacitinib pode ajudar a aliviar o efeito rebote que ocorre ao diminuir a dosagem de oclacitinib, em comparação com o uso de oclacitinib em monoterapia para o tratamento da DAC.. INTRODUCCIÓN: Los ácidos grasos poliinsaturados (PUFA) pueden ser beneficiosos en el tratamiento de la dermatitis atópica canina (cAD). Un producto comercial PCSO-524 que contiene PUFA ha demostrado efectos antiinflamatorios en perros. HIPÓTESIS/OBJETIVOS: Evaluar la eficacia de PCSO-524, en combinación con oclacitinib en perros con cAD. ANIMALES: Diecisiete perros de propietarios particulares con cAD. MATERIALES Y MÉTODOS: Ensayo controlado, al azar, doble ciego. Todos los perros fueron tratados con oclacitinib (0,4-0,6 mg/kg dos veces al día durante 14 días, luego una vez al día hasta el Día (D)42. Se dividieron al azar en dos grupos. PCSO-524 (n = 9) y aceite de girasol (n = 8). El estado clínico se evaluó mediante el índice de extensión y gravedad de la dermatitis atópica canina, cuarta revisión (CADESI-04) y la escala análoga visual de prurito (pVAS) al inicio (D0), D14, D28 y D42. La pérdida de agua transepidérmica (TEWL) se midió en los mismos puntos de tiempo. RESULTADOS: las puntuaciones de CADESI disminuyeron significativamente después del tratamiento y hubo una diferencia significativa entre PCSO-524 y el grupo de control en D28 (p = 0,04) y D42 (p = 0,03). El grupo PCSO-524 también demostró una pVAS significativamente menor en D28 y D42 (p < 0,001 y p < 0,001) en comparación con D0, mientras que se observaron diferencias significativas en el grupo de control en D14 y D28 (p < 0,01 y p = 0,04), y no en D42 (p = 0,12). La TEWL media mostró una disminución significativa en D28 y D42 en el grupo PCSO-524, en comparación con el grupo control (p = 0,002 y p < 0,001). CONCLUSIONES Y RELEVANCIA CLÍNICA: la combinación de PCSO-524 y oclacitinib puede ayudar a aliviar el efecto rebote que se produce cuando se reduce gradualmente la dosis de oclacitinib, en comparación con el uso de oclacitinib solo para el tratamiento de la cAD.. Mehrfach ungesättigte Fettsäuren (PUFA) können beim Management der caninen atopischen Dermatitis (cAD) hilfreich sein. Ein kommerzielles Produkt PCSO-524, welches PUFA enthält, hat entzündungshemmende Wirkung bei Hunden bewiesen.. Das Ziel war eine Evaluierung der Wirksamkeit von PCSO-524 in Kombination mit Oclacitinib bei Hunden mit cAD.. Siebzehn Hunde mit cAD, welche in Privatbesitz waren.. Es handelt sich um eine randomisierte, doppelblinde kontrollierte Studie. Alle Hunde wurden mit Oclacitinib (0,4-0,6 mg/kg) zweimal täglich 14 Tage lang behandelt, danach einmal täglich bis zum Tag (D) 42. Die Hunde wurden zufällig in zwei Gruppen eingeteilt: PCSO-524 (n = 9) und Sonnenblumenöl (n = 8). Der klinische Status wurde mittels Canine Atopic Dermatitis Extent and Severity Index, 4te Auflage (CADESI-04) und der Pruritus Visual Analog Scale (pVAS) zum Ausgangspunkt (D0), D14, D28 und D42 erfasst. Der transepidermale Wasserverlust (TEWL) wurde zu diesen Zeitpunkten ebenfalls erfasst.. Die CADESI Werte nahmen nach der Behandlung signifikant ab und es bestand ein signifikanter Unterschied zwischen der PCSO-524 und der Kontrollgruppe am D28 (p = 0,04) und D42 (p = 0,03). Die PCSO-524 Gruppe zeigte außerdem eine signifikant reduzierte pVAS am D28 und D42 (p < 0,001 und p < 0,001) im Vergleich zu D0, während in der Kontrollgruppe signifikante Unterschiede am D14 und D28 (p < 0,01 und p = 0,04), aber nicht am D42 (p = 0,12) festgestellt wurden. Der durchschnittliche TEWL zeigte am D28 und D42 (p = 0,002 und p < 0,001) in der PCSO-524 Gruppe im Vergleich zur Kontrollgruppe eine signifikante Reduktion.. Die Kombination von PCSO-524 und Oclacitinib könnte im Vergleich zum alleinigen Einsatz von Oclacitinib dabei helfen, den Rebound Effekt, der bei der Reduzierung der Oclacitinib Dosis eintritt, auszugleichen.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Fatty Acids, Unsaturated; Humans; Pruritus

Oclacitinib maleate (Apoquel®, Zoetis Inc.) is commonly used around the world for the control/treatment of pruritus associated with allergic dermatitis and the control/treatment of atopic dermatitis in dogs at least 12 months of age. A new flavored chewable formulation of oclacitinib has been developed where more than 90% of doses offered to dogs were freely accepted when tested in clinical trials. The objective of this study was to determine whether the new chewable formulation of oclacitinib has a similar onset of anti-pruritic activity as the original oclacitinib film-coated tablets (FCT). Twenty-one laboratory beagle dogs were randomized to treatment and received placebo, 0.4-0.6 mg/kg oclacitinib FCT or 0.4-0.6 mg/kg flavored chewable oclacitinib tablet (n = 7/group). Efficacy was measured by assessing reduction in pruritus 1-3 h post-administration of treatments. Pruritus was induced by injecting canine IL-31, intravenously (2.5 μg/kg), approximately 15 min prior to the pruritus observation window. Results from this study demonstrated both oclacitinib FCT and the flavored chewable oclacitinib tablet significantly reduced IL-31-induced pruritus within 1-3 h post-dosing compared to placebo (p = .0069 and .0113, respectively), suggesting the new formulation of oclacitinib chewable tablets works as quickly to reduce pruritus in dogs as the oclacitinib FCT.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Maleates; Pruritus; Pyrimidines; Sulfonamides

Oclacitinib is an effective systemic therapy for dogs with atopic dermatitis (AD). Few studies have evaluated concurrent topical treatment with oclacitinib in dogs.. To evaluate the efficacy and safety of combination therapy of oclacitinib and 0.0584% hydrocortisone aceponate (HCA) spray in dogs with AD.. Eighteen dogs with AD.. This study was a randomized, double-blinded, placebo-controlled trial. All dogs were treated with oclacitinib (0.4-0.6 mg/kg twice daily for 14 days, then once daily for 14 days) and randomized to receive either HCA spray or placebo spray, applied once daily for seven days then every other day through to Day (D)28. Clinical assessments included the Canine Atopic Dermatitis Extent and Severity Index, 4. The mean CADESI-4 and PVAS scores were significantly reduced on D7 and D14 compared to D0 in both groups (P < 0.05). From D14 to D21, CADESI-4 and PVAS scores were significantly increased in the placebo group (P < 0.005), and not in the HCA-treated group. The mean reduction from baseline of the HCA-treated group was significantly higher than that of the placebo group for the PVAS and CADESI-4 on D21 (59.9% versus 27.6%, P = 0.0216) and D28 (56.0% versus 30.5%, P = 0.0109), respectively. One dog in the HCA-treated group was withdrawn as a consequence of developing diarrhoea.. Topical application of 0.0584% HCA spray may be useful for preventing exacerbation of pruritus and clinical lesions when tapering oclacitinib therapy in dogs with AD.. L’oclacitinib est un traitement systémique efficace pour les chiens atteints de dermatite atopiques (cAD). Peu d’études ont évaluées un traitement topique concomitant à l’administration d’oclacitinib chez le chien.. Evaluer l’efficacité et l’innocuité de traitement combiné d’oclacitinib et d’un spray de 0,0584% d’acéponate d’hydrocortisone (HCA) chez les chiens avec cAD.. Dix-huit chiens avec cAD. MATÉRIELS ET MÉTHODES: Cette étude est randomisée, en double aveugle, contre placebo. Tous les chiens ont été traités avec de l’oclacitinib (0.4-0.6 mg/kg deux fois par jour pendant 14 jours, puis une fois par jour pendant 14 jours) et randomisés pour recevoir soit le spray d’HCA soit le placebo, appliqué une fois par jour pendant sept jours puis un jour sur deux jusqu’à jour (J) 28. Les évaluations cliniques comprennent un CADESI-04 (Canine Atopic Dermatitis Extent and Severity Index, 4. L’application topique d’un spray d’HCA à 0,0584% peut être utile pour prévenir l’aggravation du prurit et des lésions cliniques au cours de la diminution de dose d’oclacitinib chez les chiens avec cAD.. INTRODUCCIÓN: el oclacitinib es una terapia sistémica eficaz para perros con dermatitis atópica canina (cAD). Pocos estudios han evaluado el tratamiento tópico concomitante con oclacitinib en perros. OBJETIVOS: Evaluar la eficacia y seguridad de la terapia combinada de oclacitinib y el aerosol de aceponato de hidrocortisona (HCA) al 0,0584% en perros con cAD. ANIMALES: dieciocho perros con cAD. MÉTODOS Y MATERIALES: este estudio fue aleatorio, doble ciego y controlado con placebo. Todos los perros fueron tratados con oclacitinib (0,4-0,6 mg/kg dos veces al día durante 14 días, luego una vez al día durante 14 días) y fueron asignados al azar para recibir aerosol de HCA o aerosol placebo, aplicado una vez al día durante siete días y luego cada dos días hasta el día (D) 28. Las evaluaciones clínicas incluyeron el índice de gravedad y extensión de la dermatitis atópica canina, cuarta revisión (CADESI-04) y la escala analógica visual de prurito (pVAS) cada siete días, y análisis de sangre y orina cada 14 días. RESULTADOS: las puntuaciones medias de CADESI-04 y pVAS se redujeron significativamente en D7 y D14 en comparación con D0 en ambos grupos (P <0,05). De D14 a D21, las puntuaciones de CADESI-04 y pVAS aumentaron significativamente en el grupo de placebo (P <0,005) y no en el grupo tratado con HCA. La reducción media desde el inicio del grupo tratado con HCA fue significativamente mayor que la del grupo de placebo para pVAS y CADESI-04 en D21 (59,9% versus 27,6%, P = 0,0216) y D28 (56,0% versus 30,5%, P = 0.0109), respectivamente. Un perro en el grupo tratado con HCA fue retirado como consecuencia del desarrollo de diarrea. CONCLUSIÓN: la aplicación tópica de un aerosol de HCA al 0,0584% puede ser útil para prevenir la exacerbación del prurito y las lesiones clínicas cuando se reduce el tratamiento con oclacitinib en perros con cAD.. Oclacitinib ist eine wirksame systemische Therapie für Hunde mit caniner atopischer Dermatitis (cAD). Nur wenige Studien haben eine gleichzeitige topische Behandlung bei Oclacitinib Verabreichung bei Hunden untersucht.. Eine Evaluierung der Wirksamkeit und Sicherheit der Kombinationstherapie von Oclacitinib und 0,0584%igem Hydrocortison Aceponate (HCA) Spray bei Hunden mit cAD.. Achtzehn Hunde mit cAD.. Es handelte sich hierbei um eine randomisierte, doppel-blinde, Plazebo-kontrollierte Studie. Es wurden alle Hunde mit Oclacitinib (0,4-0,6 mg/kg zweimal täglich für 14 Tage, danach einmal täglich für 14 Tage behandelt) und erhielten zufällig entweder HCA oder Plazebo Spray, welcher zunächst sieben Tage lang einmal täglich, dann jeden zweiten Tag bis zum Tag (D) 28 angewendet wurde. Die klinische Beurteilung erfolgte mittels Canine Atopic Dermatitis Extent and Severity Index, 4. Iteration (CADESI-04) und der Pruritus Visual Analog Scale (pVAS) alle sieben Tage, sowie einer Blut- und Urinuntersuchung alle 14 Tage.. Die durchschnittlichen CADESI-04 und pVAS Scores waren am D7 und am D14 im Vergleich zu D0 in beiden Gruppen (P < 0,05) signifikant reduziert. Von D14 bis D21 waren die CADESI-04 und die pVAS Scores in der Plazebogruppe signifikant erhöht (P < 0,005), allerdings nicht in der mit HCA-behandelten Gruppe. Die durchschnittliche Verminderung vom Ausgangspunkt der HCA-behandelten Gruppe lag am D21 (59,9% versus 27,6%, P = 0,0216) bzw am D28 (56,0% versus 30,5%, P = 0,0109) signifikant höher für pVAS und CADESI-04 als jene der Plazebogruppe. Ein Hund aus der HCA-behandelten Gruppe entwickelte Durchfall und wurde aus der Studie genommen.. Die topische Verabreichung von 0,0584%igem HCA Spray könnte sich bei Hunden mit cAD gut auf eine Verschlimmerung des Pruritus und der klinischen Läsionen auswirken, wenn die Behandlungsdosis mit Oclacitinib langsam reduziert wird.. 背景: 对于特应性皮炎(cAD)患犬, 奥拉替尼是一种有效的全身性治疗药物。很少有研究评估犬同时接受奥拉替尼和外部治疗的效果。 目的: 评估奥拉替尼和0.0584%氢化可的松丙酸酯(HCA)喷雾剂联合治疗, cAD犬的有效性和安全性。 动物: 18只cAD犬。 方法和材料: 本研究是一项随机、双盲、安慰剂对照试验。所有犬均接受奥拉替尼治疗 (0.4-0.6 mg/kg, 每日两次, 持续14天, 然后每日一次, 持续14天) , 并随机接受HCA喷雾剂或安慰剂喷雾剂, 每日一次, 持续7天, 然后隔日一次, 直至第28天(D)。临床评估包括第4版犬特应性皮炎严重程度和指数 (CADESI-04)和瘙痒视觉模拟量表(pVAS), 每7天一次, 以及血液和尿液检查, 每14天一次。 结果: 与D0相比, 两组中D7和D14的平均CADESI-04和pVAS评分显著降低(P < 0.05)。从D14至D21, 安慰剂组的CADESI-04和pVAS评分显著增加(P < 0.005), 而HCA治疗组无显著增加。D21(59.9%与27.6%,P = 0.0216) 和D28(56.0%与30.5%,P = 0.0109) 时, HCA治疗组的pVAS和CADESI-04相对于基线的平均下降程度显著高于安慰剂组。HCA治疗组中的1只犬因发生腹泻而退出研究。 结论: 在cAD犬逐渐减少奥拉替尼治疗时, 外部应用0.0584%HCA喷雾剂可能有助于预防瘙痒和临床病变加重。.. 背景: オクラシチニブは、犬アトピー性皮膚炎（cAD）の犬に効果的な全身療法である。犬におけるオクラシチニブとの併用外用療法を評価した研究はほとんどない。 目的: 本研究の目的は、cADの犬におけるオクラシチニブ及び0.0584％アセポン酸ヒドロコルチゾン（HCA）スプレーの併用療法の有効性及び安全性を評価することであった。 被験動物: cADを有する18頭の犬。 材料と方法: 本研究は、無作為化二重盲検プラセボ対照試験であった。すべての犬をオクラシチニブ（0.4〜0.6 mg / kg、1日2回14日間、その後1日1回14日間）で治療し、HCAスプレーまたはプラセボスプレーのいずれかをランダムに投与し、1日1回7日間、その後隔日で28日目まで適用した。臨床評価に、犬アトピー性皮膚炎の程度及び重症度指数、4回反復（CADESI-04）及び視覚的掻痒アナログ尺度（pVAS）を7日ごとに、血液及び尿検査を14日ごとに実施した。 結果: 平均CADESI-04およびpVASスコアは、両グループのD0と比較してD7およびD14で有意に減少した（P <0.05）。 D14からD21まで、CADESI-04およびpVASスコアはプラセボ群で有意に増加し（P <0.005）、HCA治療群では増加しなかった。 HCA治療群のベースラインからの平均減少は、D21（59.9％対27.6％、P = 0.0216）およびD28（56.0％対30.5％、P = 0.0109）でプラセボ群のpVASおよびCADESI-04よりもそれぞれ有意に高かった。 HCA治療群の1頭の犬は、下痢を発症し、結果として離脱した。 結論: 0.0584％HCAスプレーによる外用塗布は、cADの犬のオクラシチニブ療法を漸減する際の掻痒症および臨床病変の悪化防止に役立つ可能性がある。.. O oclacitinib é uma terapia sistêmica eficaz para cães com dermatite atópica canina (DAC). Poucos estudos avaliaram o tratamento tópico concomitante com oclacitinib em cães.. Avaliar a eficácia e segurança da terapia combinada de oclacitinib e spray de aceponato de hidrocortisona a 0,0584% (HCA) em cães com DAC.. Dezoito cães com DAC. MÉTODOS E MATERIAIS: Este estudo foi um ensaio randomizado, duplo-cego e placebo-controle. Todos os cães foram tratados com oclacitinib (0,4-0,6 mg/kg duas vezes ao dia por 14 dias, depois uma vez ao dia por 14 dias) e randomizados para receber spray de HCA ou spray de placebo, aplicado uma vez ao dia por sete dias, em seguida, a cada dois dias até o dia (D) 28. As avaliações clínicas incluíram o Índice de Gravidade e Extensão da Dermatite Atópica Canina, 4ª iteração (CADESI-04) e a Escala Visual Analógica de prurido (pVAS) a cada sete dias, e exames de sangue e urina a cada 14 dias.. Os escores médios do CADESI-04 e pVAS foram significativamente reduzidos no D7 e D14 em comparação ao D0 em ambos os grupos (P <0,05). De D14 a D21, os escores CADESI-04 e pVAS aumentaram significativamente no grupo de placebo (P <0,005), e não no grupo tratado com HCA. A redução média em relação ao escore inicial do grupo tratado com HCA foi significativamente maior do que a do grupo placebo para o pVAS e o CADESI-04 no D21 (59,9% versus 27,6%, P = 0,0216) e no D28 (56,0% versus 30,5%, P = 0,0109), respectivamente. Um cão do grupo tratado com HCA foi retirado do estudo devido ao desenvolvimento de diarreia. CONCLUSÃO: A aplicação tópica de 0,0584% de HCA spray pode ser útil para prevenir a exacerbação do prurido e lesões clínicas ao reduzir a terapia com oclacitinib em cães com DAC.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Double-Blind Method; Hydrocortisone; Pyrimidines; Sulfonamides

Oclacitinib is a Janus-kinase inhibitor that decreases interleukin-31-induced pruritus in cats. At 0.4-0.6 mg/kg/day orally, it decreased pruritus and skin lesions in <50% of allergic cats.. To evaluate efficacy and safety of oclacitinib in feline nonflea nonfood-induced hypersensitivity dermatitis (NFNFIHD).. Forty cats with NFNFIHD.. Cats were randomly assigned to receive oclacitinib (group A, 20 cats, 0.7-1.2 mg/kg) or methylprednisolone (group B, 20 cats, 0.5-1 mg/kg) orally twice daily for 28 days. On day (D)1 and D28, lesions were evaluated using the Scoring Feline Allergic Dermatitis (SCORFAD) scale and owners assessed pruritus using a Visual Analog Scale (VAS) and quality of life (QoL) questionnaire. Results were analysed by General Linear Mixed Model (P < 0.05). Haematochemical analyses were performed on D1 and D28.. In both groups all parameters improved significantly, with no difference at either time point. Group A had a 61% mean SCORFAD and 54% pruritus VAS improvement, compared with 69% and 67% in group B; 70% of cats in group A and 75% in group B achieved a ≥ 50% reduction of pruritus VAS scores; with 60% and 80% of SCORFAD. There were five non-responders in group A and three in group B. The QoL score improved in both groups (25 and 21%). Four of 14 cats had mild increases in kidney function tests (oclacitinib group) and three of 12 cats had elevated alanine transferase (methylprednisolone group).. Oclacitinib appears to be effective for treating pruritus and lesions in cats with NFNFIHD, albeit methylprednisolone seemed to perform better.. L'oclacitinib est un inhibiteur de Janus kinase qui diminue le prurit induit par l'interleukine-31 chez le chat. A 0.4-0.6 mg/kg/jour per os, il diminue le prurit et les lésions cutanées pour <50% des chats allergiques. HYPOTHÈSES/OBJECTIFS: Evaluer l'efficacité et l'innocuité de l'oclacitinib chez les chats atteints de dermatite par hypersensibilité non liée aux puces et non liée à l'alimentation (NFNFIHD).. Quarante chats NFNFIHD. MÉTHODES: Les chats ont été répartis au hasard pour recevoir soit de l'oclacitinb (groupe A, 20 chats, 0.7-1.2 mg/kg) ou de la méthylprednisolone (groupe B, 20 chats, 0.5-1 mg/kg) oralement deux fois par jour pendant 28 jours. Aux jours (D)1 et D28, les lésions ont été évaluées par SCORFAD (Scoring Feline Allergic Dermatitis) et les propriétaires ont évalués le prurit à l'aide d'une échelle visuelle analogue (VAS) et un questionnaire de qualité de vie (QoL). Les résultats ont été analysés par General Linear Mixed Model (P < 0.05). Les analyses hémato-biochimiques ont été réalisées à D1 et D28. RÉSULTATS: Dans les deux groupes, tous les paramètres se sont significativement améliorés sans différence quelque soit le moment. Le groupe A a fait un score de 61% de SCORAD et une amélioration de 54% de VAS en comparaison avec 69% et 67% pour le groupe B; 70% des chats du groupe A et 75% des chats du groupe B ont montré une diminution ≥ 50% des scores de VAS de prurit; avec 60% et 80% de SCORFAD. Il y avait 5 non répondant dans le groupe A et trois dans le groupe B. Le score de QoL s'est amélioré dans les deux groupes (25 et 21%). Quatre des 14 chats avaient une augmentation modérée des valeurs rénales (groupe oclacitinib) et trois des 12 chats avaient une transférase alanine élevée (group méthylprednisolone).. L'oclacitinib semble efficace pour le traitement du prurit et des lésions chez les chats avec NFNFIHD bien que la méthylprednisolone semble être plus efficace.. INTRODUCCIÓN: el oclacitinib es un inhibidor de la Janus-quinasa que disminuye el prurito inducido por interleuquina 31 en los gatos. A una dosis de 0,4 a 0,6 mg/kg/día por vía oral, disminuyó el prurito y las lesiones cutáneas en <50% de gatos alérgicos. HIPÓTESIS/OBJETIVOS: evaluar la eficacia y la seguridad del oclacitinib en dermatitis felina por hipersensibilidad no inducida por pulgas ni alimentos (NFNFIHD). ANIMALES: Cuarenta gatos con NFNFIHD. MÉTODOS: los gatos fueron asignados al azar para recibir oclacitinib (grupo A, 20 gatos, 0,7-1,2 mg/kg) o metilprednisolona (grupo B, 20 gatos, 0,5-1 mg/kg) por vía oral dos veces al día durante 28 días. En el día (D) 1 y D28, las lesiones se evaluaron utilizando la escala de Dermatitis alérgica felina (SCORFAD) y los propietarios evaluaron el prurito utilizando un cuestionario de Escala análoga visual (VAS) y calidad de vida (QoL). Los resultados se analizaron mediante un modelo general lineal mixto (P <0,05). Se realizaron análisis de química sanguínea en D1 y D28. RESULTADOS: en ambos grupos, todos los parámetros mejoraron significativamente, sin diferencia en ninguno de los puntos de tiempo. El grupo A tuvo una mejoría promedio de 61% en el SCORFAD y 54% en el VAS de prurito, en comparación con el 69% y el 67% en el grupo B; el 70% de los gatos en el grupo A y el 75% en el grupo B lograron una reducción de ≥ 50% de los valores VAS de prurito; con 60% y 80% de SCORFAD. Hubo cinco animales que no respondieron en el grupo A y tres en el grupo B. Los valores de la calidad de vida mejoraron en ambos grupos (25 y 21%). Cuatro de 14 gatos tuvieron aumentos leves en los valores clínicos de la de función renal (grupo de oclacitinib) y tres de 12 gatos tuvieron alanina transferasa elevada (grupo de metilprednisolona). CONCLUSIONES E IMPORTANCIA CLÍNICA: el oclacitinib parece ser eficaz para tratar el prurito y las lesiones en gatos con NFNFIHD, aunque la metilprednisolona parece tener mejores resultados.. Oclacitinib ist ein Janus-Kinase Inhibitor, der Interleukin-31-induzierten Juckreiz bei Katzen vermindert. Bei einer Dosis von 0,4-0,6 mg/kg/Tag per os verminderte es den Juckreiz und die Hautveränderungen bei <50% der allergischen Katzen.. Eine Evaluierung der Wirksamkeit und der Sicherheit von Oclacitnib bei Katzen mit Nonflea-Nonfood (Nicht durch Flöhe-nicht durch Futter)-induzierter Hypersensibilitätsdermatitis (NFNFIHD).. Vierzig Katzen mit NFNFIHD.. Die Katzen wurden zufällig eingeteilt, um Oclacitinib (Gruppe A, 20 Katzen; 0,7-1,2 mg/kg) oder Methylprednisolon (Gruppe B, 20 Katzen; 0,5-1 mg/kg) per os zweimal täglich 28 Tage lang zu erhalten. Am Tag (D) 1 und am D28 wurden die Veränderungen mittels Scoring Feline Allergic Dermatitis (SCORFAD) Skala evaluiert und die BesitzerInnen beurteilten den Juckreiz mittels Visual Analog Scale (VAS) und einem Quality of Life (Lebensqualität; QoL) Fragebogen. Die Ergebnisse wurden mit einem General Linear Mixed Model analysiert (P < 0,05). Eine hämatochemische Analyse wurde am Tag1 und Tag28 durchgeführt.. In beiden Gruppen verbesserten sich alle Parameter signifikant, ohne Unterschiede zu den jeweiligen Zeitpunkten. Gruppe A hatte einen 61%igen durchschnittlichen SCORFAD und 54% VAS Verbesserung des Juckreizes im Vergleich zu 69% bzw 67% in Gruppe B; 70% der Katzen in Gruppe A und 75% in Gruppe B erzielten eine ≥ 50%igeRreduktion des VAS Juckreiz Wertes; mit 60% bzw 80% SCORFAD. Es gab fünf Tiere in Gruppe A, die keine Verbesserung zeigten und drei in Gruppe B. Der QoL Wert verbesserte sich in beiden Gruppen (25 und 21%). Vier von 14 Katzen zeigten eine milde Zunahme bei einem Nierenfunktionstest (Oclacitinibgruppe) und drei von 12 Katzen zeigten eine erhöhte Alanintransferase (Methyprednisolongruppe).. Oclacitinib scheint zur Behandlung des Pruritus und der Hautveränderungen bei Katzen mit NFNFIHD wirksam zu sein, wobei allerdings Methylprednisolon eine etwas bessere Wirkung zeigte.. 背景: オクラシチニブは、猫のインターロイキン31誘発性掻痒を軽減するヤヌスキナーゼ阻害剤である。0.4〜0.6 mg / kg /日の経口投与によって、アレルギー猫の50%未満で掻痒および皮膚病変が減少した。 仮説/目的: 本研究の目的は、猫の非ノミ非食物誘発性性過敏性皮膚炎(NFNFIHD)におけるオラシチニブの有効性および安全性を評価することである。 被験動物: NFNFIHDを有する40頭の猫。 方法: 1日2回、28日間オクラシチニブ(A群、20頭の猫、0.7〜1.2mg / kg)またはメチルプレドニゾロン(B群、20頭の猫、0.5〜1mg / kg)を経口投与するように猫をランダムに割り当てた。1日目(D1)およびD28に、Scoring Feline Allergic Dermatitis (SCORFAD)尺度を使用して病変を評価し、オーナーは、Visual Analog Scale (VAS) を使用して掻痒を評価し、質問票によって生活の質(QoL)を評価した。結果は一般線形混合モデル(P <0.05)により解析した。血液生化学解析はD1およびD28に実施した。 結果: 両群において、全パラメータが有意に改善し、どちらの時点においても差を認めなかった。 B群では69%の平均SCORFADおよび67%の掻痒VASの改善と比較し、A群では61%の平均SCORFADおよび54%の掻痒VASの改善を示した。A群猫の70%、B群猫の75%が掻痒VASスコアの50%以上の減少を達成した。また、SCORFADにおいては60%および80%であった。治療に無反応な症例が A群に5頭、B群に3頭いた。両群においてQoLスコアに改善を認めた(25および21%)。 14頭中4頭の猫が腎機能検査において緩徐な上昇を示し(オラシチニブ群)、12頭中3頭の猫がアラニントランスフェラーゼに上昇を示した(メチルプレドニゾロン群)。 結論と臨床的重要性: オクラシチニブは、メチルプレドニゾロンほどではないが、NFNFIHD猫の掻痒および病変部の治療に有効であるように思われる。.. 背景: 奥克拉克替尼是一种Janus激酶抑制剂,可降低白介素-31诱导的猫瘙痒。每日口服0.4-0.6mg/kg,它可以减少<50%的猫过敏性瘙痒和皮肤病变。 假设/目的: 评估奥克拉克替尼治疗猫非跳蚤、非食物过敏性皮炎(NFNFIHD)的疗效和安全性。 动物: 四十只NFNFIHD患猫。 方法: 将猫随机分配接受奥克拉克替尼(A组、20只猫、0.7-1.2mg/kg)或甲基强的松龙(B组、20只猫、0.5-1mg / kg),每日口服两次,疗程28天。在第1天和第28天,使用猫过敏性皮炎(SCORFAD)评分表评估病变,并且让主人填写瘙痒评分表(VAS)和生活质量(QoL)问卷评价瘙痒,结果采用一般线性混合模型进行分析(P <0.05)。同时在第1天和第28天进行血液化学分析。 结果: 两组的各项指标均有明显改善,并且在任一时间点均无差异。A组的平均SCORFAD为61%,VAS改善为54%,而B组分别为69%和67%。70%A组的猫和75%B组的猫瘙痒VAS评分降低≥50%;以及60%和80%的SCORFAD。A组有5只无反应,B组有3只无反应。两组的QoL评分均有所提高(25%和21%)。奥克拉克替尼组中,14只猫中有4只肾功能指标轻度增加;而甲基强的松龙组中,12只猫中有3只丙氨酸转移酶升高。 结论和临床意义: 奥克拉克替尼对治疗NFNFIHD猫的瘙痒和病变似乎有效,但甲基强的松龙表现更好。.. O oclacitinib é um inibidor de janus-kinase que reduz o prurido induzido por interleucina-31 em gatos. Em uma dose de 0,4-0,6 mg/kg por via oral, ele foi capaz de reduzir o prurido e as lesões cutâneas em <50% dos gatos alérgicos. HIPÓTESE/OBJETIVOS: Avaliar a eficácia e a segurança do oclacitinib no tratamento da dermatite por hipersensibilidade não induzida por pulgas ou alimentos (NFNFIHD).. Quarenta gatos com NFNFIHD. MÉTODOS: Os gatos foram randomizados para receber oclacitinib (grupo a, 20 gatos, 0,7-1,2 mg/kg) ou metilprednisolona (grupo B, 20 gatos, 0,5-1,0 mg/kg) por via oral, duas vezes ao dia por 28 dias. No dia (D) 1 e D28, as lesões foram avaliadas utilizando a escala do Escore de Dermatite Alérgica Felina (Scoring Feline Allergic Dermatitis, SCORFAD) e a escala analógica visual de prurido para avalição por proprietários (VAS, visual analogue scale) e o questionário de qualidade de vida (QoL). Os resultados foram analisados pelo Modelo Linear Misto (P < 0.05). Análises hematoquímicas foram realizadas no D1 e D28.. Em ambos os grupos, todos os parâmetros melhoraram significativamente, sem diferenças significativas entre os tempos experimentais. O grupo A apresentou em média 61% de melhora no SCORFAD e 54% no prurido VAS, comparado com 69% e 67% no grupo B; 70% dos gatos do grupo A E 75% do grupo B alcançaram uma redução ≥ 50% nos escores de prurido VAS; com 60% e 80% do SCORFAD. No grupo A houve um total de cinco animais refratários e no grupo B, três. O escore QoL melhorou em ambos os grupos (25 e 21%). Quatro dos 14 gatos apresentaram aumentos discretos nos testes de função renal (grupo oclacitinib) e três de 12 gatos apresentaram aumento na alanina transferase (grupo metilprednisolona). CONCLUSÕES E IMPORTÂNCIA CLÍNICA: O oclacitinib parece ser eficaz no tratamento do prurido e lesões em gatos com NFNFIHD, apesar de aparentemente a metilprednisolona ter apresentado um melhor desempenho.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents; Cats; Dermatitis, Atopic; Dermatologic Agents; Hypersensitivity; Methylprednisolone; Pruritus; Pyrimidines; Random Allocation; Skin; Sulfonamides; Surveys and Questionnaires

Dogs with atopic dermatitis are prone to sensitization to environmental allergens due to increased skin permeability; the effect of treatments on epicutaneous sensitizations is unknown.. To evaluate if oclacitinib (i) prevents new sensitizations and (ii) affects skin barrier function.. Atopic beagle dogs.. Aim 1. Ten dogs were randomly assigned to placebo or oclacitinib while exposed epicutaneously to a novel allergen. Sensitization was assessed using serum allergen-specific IgE and clinically by development of skin reactions at the site of allergen application. Time to develop dermatitis and allergen-specific IgE were compared between groups. Aim 2. Eight dogs were randomly assigned to placebo or oclacitinib for four weeks and challenged with an allergen known to trigger flares. After a four week wash-out, dogs were crossed-over and the protocol repeated. Transepidermal water loss (TEWL) was measured on days 0 and 28 of each arm.. Aim 1. Oclacitinib significantly increased (P = 0.006) time to develop skin reactions compared to placebo. Four (of five) dogs receiving oclacitinib failed to develop skin reactions, whereas all placebo dogs developed dermatitis. There were no significant differences in allergen-specific IgE between groups. Aim 2. TEWL results were difficult to interpret. Significantly higher values were detected from the axilla in placebo compared to oclacitinib-treated dogs (P = 0.047). TEWL values were significantly higher from the inguinal area in oclacitinib (P = 0.039) treated dogs but not placebo at the end of the study.. Clinically, oclacitinib delayed development of dermatitis at the site of allergen application. TEWL results were difficult to interpret and additional studies are required for clarification.

Topics: Animals; Cross-Over Studies; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Female; Immunization; Male; Pilot Projects; Pyrimidines; Skin; Sulfonamides; Water Loss, Insensible

Ciclosporin is approved for the treatment of atopic dermatitis (AD) in dogs and has been shown to be safe and effective. Placebo-controlled studies suggest that oclacitinib is a safe and effective alternative therapy.. To evaluate the efficacy and safety of oclacitinib, in comparison to ciclosporin, for the control of AD in a blinded, randomized clinical trial, incorporating a noninferiority test at day 28.. A total of 226 client-owned dogs with a history of AD from eight sites were enrolled.. Enrolled animals were randomized to receive oral oclacitinib (0.4-0.6 mg/kg twice daily for 14 days, then once daily) or oral ciclosporin (3.2-6.6 mg/kg once daily) for 12 weeks. Owners assessed pruritus using an enhanced visual analog scale (VAS), and veterinarians assessed dermatitis using the Canine Atopic Dermatitis Extent and Severity Index (CADESI)-02.. On days 1, 2, 7, 14, 28, 56 and 84, the percentage reduction from baseline for owner-assessed pruritus changed from 25.6 to 61.0% in the oclacitinib group compared with 6.5 to 61.5% in the ciclosporin group; differences were significant at all time points up to day 28. On day 56, ciclosporin-treated dogs showed a similar decrease in pruritus to oclacitinib-treated dogs. On day 14, the percentage reduction from baseline CADESI-02 was significantly greater in the oclacitinib group (58.7%) than in the ciclosporin group (43.0%). Three times as many adverse events attributed to gastrointestinal signs were reported in the ciclosporin group compared with the oclacitinib group.. In this study of treatment for canine AD, oclacitinib had a faster onset of action and a lower frequency of gastrointestinal side effects compared with ciclosporin.

Topics: Animals; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Female; Male; Pruritus; Pyrimidines; Single-Blind Method; Sulfonamides; Treatment Outcome

Oclacitinib is safe and effective for treating dogs with pruritus associated with allergic and atopic dermatitis, based on randomized clinical trials of up to 4 months duration.. This study assessed long-term safety, efficacy and quality of life of oclacitinib-treated dogs enrolled in a compassionate use programme.. Two hundred and forty-seven client-owned dogs with allergic skin disease that had previously benefited from oclacitinib therapy.. Dogs were enrolled in an open-label study at 26 veterinary clinics. Dogs received 0.4-0.6 mg/kg oclacitinib twice a day for 14 days, then once a day for up to 630 days. Assessments were performed at ~90 day intervals. Owners completed a quality-of-life survey and assessed pruritus using a Visual Analog Scale (VAS) at each clinic visit. Veterinarians assessed dermatitis using a similar VAS. Abnormal health events, concomitant medication and clinical pathology results were summarized.. Visual Analog Scale scores showed improvement from baseline at all time points. The percentage of dogs showing ≥50% reduction from baseline on day 90 was 63.9% for pruritus and 66.4% for dermatitis. Owners saw a positive impact on quality of life in >91% of all dogs. Urinary tract infection/cystitis, vomiting, otitis, pyoderma and diarrhoea were the most frequently reported (>5% of dogs) abnormal clinical signs. Haematology and serum chemistry means remained within the normal reference ranges. Concomitant medications were well tolerated.. Results indicated that oclacitinib was safe and efficacious for long-term use and improved the quality of life for dogs in this study.

Topics: Animals; Compassionate Use Trials; Dermatitis, Allergic Contact; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Drug Administration Schedule; Female; Male; Pruritus; Pyrimidines; Quality of Life; Sulfonamides; Treatment Outcome; Visual Analog Scale

Oral glucocorticoids are widely used to reduce pruritus and dermatitis associated with allergic dermatitis. Data suggest that oclacitinib, a Janus kinase inhibitor, is a safe and effective alternative.. To evaluate the efficacy and safety of oclacitinib compared with prednisolone for the control of pruritus associated with allergic dermatitis in a single-masked, controlled clinical trial with a randomized complete block design.. Client-owned dogs (n = 123) with a presumptive diagnosis of allergic dermatitis and moderate to severe pruritus as assessed by the pet owner were enrolled.. Dogs were randomized to treatment with either oclacitinib (0.4-0.6 mg/kg orally twice daily for 14 days, then once daily) or prednisolone (0.5-1.0 mg/kg once daily for 6 days, then every other day) for 28 days. An enhanced visual analog scale (VAS) was used by owners to assess pruritus and by veterinarians to assess dermatitis, at all time points assessed.. Both treatments produced a rapid onset of efficacy within 4 h. The mean reductions in pruritus and dermatitis scores were not significantly different between the treatments except on day 14, when reductions were more pronounced for oclacitinib than prednisolone (P = 0.0193 for owner pruritus scores; P = 0.0252 for veterinarian dermatitis scores). Adverse events were reported with similar frequency in both groups.. In this study, both oclacitinib and prednisolone provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with substantial improvement in pruritus, reported by owners, and dermatitis, reported by veterinarians.

Topics: Administration, Oral; Animals; Australia; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Drug Administration Schedule; Female; Glucocorticoids; Male; Prednisolone; Pruritus; Pyrimidines; Single-Blind Method; Sulfonamides; Treatment Outcome

Pruritus is the hallmark clinical sign of atopic dermatitis (AD) in dogs. Preliminary study results suggest that oclacitinib, a selective Janus kinase inhibitor, could reduce pruritus and associated inflammatory skin lesions in dogs with AD.. The objective was to evaluate efficacy and safety of oclacitinib (Apoquel®) for the control of AD in a randomized, double-blind, placebo-controlled trial.. Clinicians at 18 specialty clinics enrolled client-owned dogs (n = 299) with a history of chronic AD.. Dogs were randomized to receive either oclacitinib (0.4-0.6 mg/kg twice daily for 14 days and then once daily for up to 112 days) or an excipient-matched placebo. Owners assessed visual analog scale (VAS) scores of pruritus on days 0, 1, 2, 7, 14, 28, 56, 84 and 112. Clinicians assessed Canine AD Extent and Severity Index (CADESI-02) scores on days 0, 14, 28, 56, 84 and 112.. On days 1, 2, 7, 14 and 28, oclacitinib-treated dogs had a 29.5, 42.3, 61.5, 66.7 and 47.4% reduction from baseline in owner-assessed pruritus scores, respectively, compared with a 6.5, 9.1, 6.5, 3.9 and 10.4% reduction in placebo-treated dogs. On days 14 and 28, dermatologists recorded a 48.4% reduction in CADESI-02 scores in oclacitinib-treated dogs compared with a 1.7% reduction and a 3.6% increase in placebo-treated dogs. After day 28, >86% of all placebo-treated dogs had moved to an open-label study, making between-group comparisons biased. Differences were significant at all time points assessed (P < 0.0001).. Oclacitinib provided rapid, effective and safe control of AD, with substantial improvement in VAS and CADESI-02 scores.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Female; Male; Pyrimidines; Sulfonamides

Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction.. We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months.. We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT.. Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-β1 were measured by enzyme-linked immunosorbent assay.. The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-β1 serum concentrations between the five groups.. Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.. Les chiens atopiques sont souvent traités avec une immunothérapie spécifique d'allergène (AIT) et des doses concomitantes de ciclosporine ou d'oclacitinib pour atténuer leurs signes cliniques. Les deux médicaments pourraient affecter l'induction de la tolérance appropriée en inhibant l'induction des lymphocytes T régulateurs (Treg). HYPOTHÈSE/OBJECTIFS: Nous avons évalué le nombre de cellules Treg et les taux sériques d'interleukine (IL)-10 et de TGF-β-1 chez des chiens diagnostiqués avec une dermatite atopique (DA) et traités avec succès par la ciclosporine ou l'oclacitinib pendant neuf mois ou plus.. Nous avons inclus 15 chiens recevant de l'oclacitinib, 14 chiens traités par ciclosporine, 15 chiens sains, 13 chiens atteints de DA modérée à sévère non traitée et 15 chiens atopiques contrôlés par AIT. MATÉRIELS ET MÉTHODES: Les pourcentages de lymphocytes T CD4+CD25+FOXP3+ du sang périphérique ont été déterminés par cytométrie de flux. Les concentrations sériques d'IL-10 et de TGF-β1 ont été mesurées par dosage immuno-enzymatique. RÉSULTATS: Le pourcentage de cellules Treg dans le groupe ciclosporine était significativement plus faible par rapport au groupe sain (p = 0,0003), au groupe AD non traité (p = 0,0056) ou au groupe AIT (p = 0,0186). Il n'y avait pas de différence significative dans les pourcentages de cellules Treg entre le groupe ciclosporine et oclacitinib, ni entre l'oclacitinib et les chiens sains non traités AD ou traités AIT. Aucune différence significative n'a été détectée dans les concentrations sériques d'IL-10 et de TGF-β1 entre les cinq groupes.. Des pourcentages de cellules Treg plus faibles chez les chiens traités à la ciclosporine suggèrent un impact de ce médicament sur cette population cellulaire ; cependant, cela ne signifie pas nécessairement qu'il diminue la tolérance. La fonctionnalité et la production de cytokines peuvent être plus importantes que le nombre de cellules Treg. D'autres études évaluant les résultats du traitement des chiens recevant l'AIT et des médicaments concomitants sont nécessaires pour montrer la pertinence clinique.. INTRODUCCIÓN: los perros atópicos a menudo se tratan con inmunoterapia específica para alérgenos (AIT) y dosis simultáneas de ciclosporina u oclacitinib para aliviar sus signos clínicos. Ambos fármacos podrían afectar la inducción de tolerancia adecuada al inhibir la inducción de células T reguladoras (Treg). HIPÓTESIS/OBJETIVOS: Evaluamos el número de células Treg y los niveles séricos de interleuquina (IL)-10 y factor de crecimiento transformante-beta (TGF-β)1 en perros diagnosticados con dermatitis atópica (AD) y tratados con éxito con ciclosporina u oclacitinib durante nueve o mas meses ANIMALES: Incluimos 15 perros que recibieron oclacitinib, 14 perros tratados con ciclosporina, 15 perros sanos, 13 perros con AD de moderada a grave no tratada y 15 perros atópicos controlados con AIT. MATERIALES Y MÉTODOS: Los porcentajes de células T CD4+CD25+FOXP3+ en sangre periférica se determinaron mediante citometría de flujo. Las concentraciones séricas de IL-10 y TGF-β1 se midieron mediante ensayo inmunoabsorbente ligado a enzimas. RESULTADOS: El porcentaje de células Treg en el grupo de ciclosporina fue significativamente menor en comparación con el grupo sano (p = 0,0003), el grupo AD no tratado (p = 0,0056) o el grupo AIT (p = 0,0186). No hubo diferencias significativas en los porcentajes de células Treg entre el grupo de ciclosporina y oclacitinib, ni entre el oclacitinib y los perros sanos, no tratados con AD o tratados con AIT. No se detectaron diferencias significativas en las concentraciones séricas de IL-10 y TGF-β1 entre los cinco grupos. CONCLUSIONES Y RELEVANCIA CLÍNICA: Los porcentajes más bajos de células Treg en los perros tratados con ciclosporina sugieren un impacto de este fármaco en esta población celular; sin embargo, no significa necesariamente que disminuya la tolerancia. La funcionalidad y la producción de citoquinas pueden ser más importantes que el número de células Treg. Se necesitan más estudios que evalúen el resultado del tratamiento de perros que reciben AIT y medicamentos concurrentes para mostrar relevancia clínica.. Atopische Hunde werden oft mit Allergen-spezifischer Immuntherapie (AIT) gemanagt, wobei gleichzeitig Ciclosporin oder Oclacitinib verabreicht werden, um ihre klinischen Zeichen zu lindern. Beide Medikamente können die Toleranzinduktion durch eine Inhibition der regulatorischen T Zellen (Treg) Induktion beeinflussen.. Wir evaluierten die Treg Zellzahlen und Serum Interleukin (IL)-10 und Transforming Growth Factor-beta (TGF-β) Werte bei Hunden, die mit einer atopischen Dermatitis (AD) diagnostiziert worden waren und entweder mit Ciclosporin oder mit Oclacitinib für neun Monate oder länger erfolgreich behandelt worden waren.. Wir inkludierten 15 Hunde, die Oclacitinib erhielten, 14 Hunde, die mit Ciclosporin behandelt worden waren, 15 gesunde Hunde, 13 Hunde mit unbehandelter moderater-bis-hochgradiger AD und 15 atopische Hunde, die mit AIT kontrolliert waren.. Periphere Blut CD4+CD25+FOXP3+ T-Zell Prozentanteile wurden mittels Flowzytometrie bestimmt. Serumkonzentrationen von IL-10 und TGF-β wurden mittels Enzym-linked Immunosorbent Assay gemessen.. Der Prozentanteil der Treg Zellen in der Ciclosporingruppe war signifikant niedriger im Vergleich zur gesunden Gruppe (p = 0,0003), zur nichtbehandelten AD-Gruppe (p = 0,0056), oder der AIT-Gruppe (p = 0,0186). Es bestand kein signifikanter Unterschied zwischen den prozentualen Anteilen der Treg Zellen zwischen Ciclosporin und der Oclacitinib Gruppe, und auch nicht zwischen der Oclacitinib und der gesunden, nichtbehandelten AD-Gruppe, oder den AIT-behandelten Hunden. Es wurden keine signifikanten Unterschiede zwischen IL-10 und TGF-β1 Serumkonzentrationen zwischen den fünf Gruppen gefunden.. Niedrigere Prozentanteile der Treg Zellen bei den Ciclosporin-behandelten Hunden weisen darauf hin, dass dieses Medikament auf diese Zellpopulation einen Einfluss hat; es bedeutet jedoch nicht unbedingt, dass es die Toleranz vermindert. Die Funktionalität und die Ciclosporin Produktion könnte wichtiger sein als die Anzahl der Treg Zellen. Weitere Studien sind nötig, die den Behandlungserfolg bei Hunden, die AIT und gleichzeitig Medikamente erhalten, evaluieren, um die klinische Relevanz zu zeigen.. 背景: アトピー犬は、しばしばアレルゲン特異的免疫療法(AIT)を行い、同時にシクロスポリンやオクラシチニブを投与して臨床症状を軽減している。両薬剤は、制御性T細胞(Treg)の誘導を阻害することにより、適切な寛容誘導に影響を与える可能性がある。 仮説/目的: 本研究の目的は、 アトピー性皮膚炎(AD)と診断され、シクロスポリンまたはオクラシチニブによる9ヶ月以上の治療に成功した犬において、Treg細胞数、血清インターロイキン(IL)-10およびトランスフォーミング増殖因子-β(TGF-β)1レベルを評価することであった。 供試動物: オクラシチニブ投与犬15頭、シクロスポリン投与犬14頭、健常犬15頭、未治療の中等度から重度のAD犬13頭、AITでコントロールしたアトピー犬15頭を対象とした。 材料と方法: 末梢血CD4+CD25+FOXP3+ T細胞の割合をフローサイトメトリーで測定した。血清中のIL-10およびTGF-β1濃度は、酵素結合免疫吸着法で測定した。 結果: シクロスポリン投与群では、健常群(p=0.0003)、AD未治療群(p=0.0056)、AIT群(p=0.0186)と比較して、Treg細胞の割合が有意に低下した。シクロスポリン群とオクラシチニブ群、オクラシチニブ群と健常群、AD未治療群、AIT治療群との間でもTreg細胞の割合に有意差はなかった。IL-10およびTGF-β1血清濃度には5群間で有意差は検出されなかった。 結論と臨床的関連性: シクロスポリン投与犬におけるTreg細胞の割合の低下は、シクロスポリンがこの細胞集団に影響を与えることを示唆していた。しかし、それは必ずしも耐性を低下させることを意味するものではない。機能性やサイトカイン産生は、Treg細胞数よりも重要である可能性がある。臨床的な関連性を示すためには、AITと併用薬を投与された犬の治療成績を評価する更なる研究が必要である。.. 背景: 特应性犬通常通过过敏原特异性免疫治疗 (AIT) 和同时给予环孢素或奥拉替尼缓解其临床症状。两种药物均可能通过抑制调节性 T 细胞 (Treg) 诱导影响适当的耐受诱导。 假设/目的: 我们在诊断为特应性皮炎 (AD) 并成功接受环孢素或奥拉替尼治疗9个月或以上的犬中评价了 Treg 细胞数量以及血清白细胞介素 (IL)-10 和转化生长因子-β (TGF-β)1水平。 动物: 我们纳入了15只接受奥拉替尼的犬、14只接受环孢素治疗的犬、15只健康犬、13只未治疗的中度至重度 AD 犬和15只接受 AIT 控制的特应性犬。 材料和方法: 使用流式细胞术测定外周血CD4 + CD25 + FOXP3 + T细胞百分比。采用酶联免疫吸附法检测血清 IL-10 和TGF-β1的浓度。 结果: 环孢素组的 Treg 细胞百分比显著低于健康组 (p = 0.0003)、未治疗 AD 组 (p = 0.0056) 或 AIT 组 (p = 0.0186)。环孢素和奥拉替尼组、奥拉替尼和健康、未治疗 AD 或 AIT 治疗犬之间的 Treg 细胞百分比无显著差异。5组间 IL-10 和TGF-β1血清浓度未检测到明显差异。 结论和临床相关性: 环孢素给药犬中较低的 Treg 细胞百分比表明该药物对该细胞群有影响；然而，这并不一定意味着其会降低耐受性。功能和细胞因子的产生可能比 Treg 细胞的数量更重要。需要进一步研究评价接受 AIT 和伴随药物的犬的治疗结果，以显示临床相关性。.. Cães atópicos geralmente são tratados com imunoterapia alérgeno-específica (AIT) e dosagens concomitantes de ciclosporina ou oclacitinib para aliviar seus sinais clínicos. Ambas as drogas podem afetar a indução de tolerância adequada ao inibir a indução de células T reguladoras (Treg). HIPÓTESE/OBJETIVOS: Avaliamos o número de células Treg e os níveis séricos de interleucina (IL)-10 e fator transformador de crescimento beta (TGF-β)1 em cães diagnosticados com dermatite atópica (DA) e tratados com sucesso com ciclosporina ou oclacitinib por nove ou mais meses.. Foram incluídos 15 cães recebendo oclacitinib, 14 cães tratados com ciclosporina, 15 cães saudáveis, 13 cães com DA moderada a grave não tratada e 15 cães atópicos controlados com AIT. MATERIAIS E MÉTODOS: As porcentagens de células T CD4+CD25+FOXP3+ do sangue periférico foram determinadas por citometria de fluxo. As concentrações séricas de IL-10 e TGF-β1 foram medidas por ensaio imunoenzimático.. A porcentagem de células Treg no grupo ciclosporina foi significativamente menor em comparação ao grupo saudável (p = 0,0003), ao grupo DA não tratado (p = 0,0056) ou ao grupo AIT (p = 0,0186). Não houve diferença significativa nas porcentagens de células Treg entre o grupo ciclosporina e oclacitinib, nem o oclacitinib e os cães saudáveis, ou oclacitinib e os cães com DA não tratados ou tratados com AIT. Não foram detectadas diferenças significativas nas concentrações séricas de IL-10 e TGF-β1 entre os cinco grupos. CONCLUSÕES E RELEVÂNCIA CLÍNICA: Percentagens mais baixas de células Treg nos cães tratados com ciclosporina sugerem um impacto deste fármaco nesta população de células; no entanto, isso não significa necessariamente que diminui a tolerância. A funcionalidade e a produção de citocinas podem ser mais importantes do que o número de células Treg. Mais estudos avaliando o resultado do tratamento de cães recebendo AIT e drogas concomitantes são necessários para mostrar a relevância clínica.

Topics: Animals; Cyclosporine; Dermatitis, Atopic; Dog Diseases; Dogs; Immune Tolerance; Interleukin-10; T-Lymphocytes, Regulatory; Transforming Growth Factor beta; Transforming Growth Factor beta1

Mesenchymal stem cells (MSCs) are a promising tool for treating immune disorders. However, the immunomodulatory effects of canine MSCs compared with other commercialized biologics for treating immune disorders have not been well studied. In this study we investigated the characteristics and immunomodulatory effects of canine amnion membrane (cAM)-MSCs. We examined gene expression of immune modulation and T lymphocytes from activated canine peripheral blood mononuclear cell (PBMC) proliferation. As a result, we confirmed that cAM-MSCs upregulated immune modulation genes (TGF-β1, IDO1 and PTGES2) and suppressed the proliferation capacity of T cells. Moreover, we confirmed the therapeutic effect of cAM-MSCs compared with oclacitinib (OCL), the most commonly used Janus kinase (JAK) inhibitor, as a treatment for canine atopic dermatitis (AD) using a mouse AD model. As a result, we confirmed that cAM-MSCs with PBS treatment groups (passage 4, 6 and 8) compared with PBS only (PBS) though scores of dermatologic signs, tissue pathologic changes and inflammatory cytokines were significantly reduced. In particular, cAM-MSCs were more effective than OCL in the recovery of wound dysfunction, regulation of mast cell activity and expression level of immune modulation protein. Interestingly, subcutaneous injection of cAM-MSCs induced weight recovery, but oral administration of oclacitinib induced weight loss as a side effect. In conclusion, this study suggests that cAM-MSCs can be developed as a safe canine treatment for atopic dermatitis without side effects through effective regeneration and immunomodulation.

Topics: Amnion; Animals; Dermatitis, Atopic; Dog Diseases; Dogs; Immunomodulation; Leukocytes, Mononuclear; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Regeneration

Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota.. Staphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin.. Dysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota. Video Abstract.

Topics: Animals; Bacteria; Dermatitis, Atopic; DNA, Mitochondrial; Dogs; Dysbiosis; Humans; Microbiota; Quality of Life

The aim of this study was to assess the efficacy of a new therapeutic regimen of oclacitinib for the control of feline atopic skin syndrome (FASS) and to correlate plasma levels of this drug with clinical effects.. Twenty-eight client-owned cats with a clinical diagnosis of FASS were recruited. Oclacitinib was administered at 1 mg/kg q12h for 2 weeks and then at 1 mg/kg q24h for a further 2 weeks. At the study outset (D0), and 7 (D7) and 28 (D28) days after starting treatment, clinical lesions were assessed using a validated scoring system (SCORing Feline Allergic Dermatitis [SCORFAD]) and pruritus was graded via an adapted visual analogue scale (PVAS). At the same time points, plasma oclacitinib levels and haematological variables were measured.. Oclacitinib emerged as being safe and effective to control clinical signs of FASS. A mean dose of 1 mg/kg, even without extending twice-daily treatment beyond the first 2 weeks, could be a suitable therapeutic regimen. Plasma drug levels did not seem useful to predict clinical response during treatment.

Topics: Animals; Cat Diseases; Cats; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Pyrimidines; Sulfonamides

Canine atopic dermatitis (cAD) is a chronic disease characterised by hypersensitivity to environmental allergens. Oclacitinib maleate selectively inhibits pro-inflammatory mediators associated with cAD. However, the impact of chronic oclacitinib use on immunocompetence requires further investigation.. Herein, we examined the potential immunomodulatory effects of prolonged oclacitinib treatment in dogs.. Thirteen privately owned dogs with cAD, treated with 0.4-0.6 mg/kg oclacitinib for 12 months.. Pruritus level was evaluated using a pruritus Visual Analog Scale (pVAS) and the canine atopic dermatitis extent and severity index, 4. Oclacitinib treatment significantly reduced pVAS and CADESI-04 scores, by 51% and 86.7%, respectively. Flow cytometric analysis revealed increased CD4+ and CD14+ lymphocyte populations. The cytokine profile at 360 days after treatment initiation was similar to that before treatment and was not associated with clinical relapse.. Oclacitinib, when administered at the currently labelled dose for one year, is associated with a significant increase in circulating CD4+ T cells, but does not alter cytokine production from antigen-stimulated T cells. The results reported do not support evidence for immunosuppression mediated by the mechanisms evaluated in this study.. 背景: 犬特应性皮炎(cAD)是一种慢性疾病，特征为对环境过敏原过敏。奥拉替尼选择性抑制与cAD相关的促炎介质。然而，需要进一步研究长期使用奥拉替尼对免疫力的影响。 目的: 为此，我们检查了长期接受奥拉替尼治疗的犬的潜在免疫调节作用。 动物: 13只患有cAD的宠物犬，接受0.4-0.6 mg/kg奥拉替尼治疗12个月。 方法和材料: 使用瘙痒视觉模拟量表(pVAS)评价瘙痒水平，采集样本进行常规实验室分析，并使用流式细胞术分析淋巴细胞亚型。在粉尘螨抗原体外刺激后，分析了CD4. La dermatite atopique canine (DAC) est une maladie chronique caractérisée par une hypersensibilité aux allergènes environnementaux. Le maléate d'oclacitinib inhibe sélectivement les médiateurs pro-inflammatoires associés à la DAC. Cependant, l'impact de l'utilisation chronique d'oclacitinib sur l'immunocompétence nécessite une étude plus approfondie.. Ici, nous avons examiné les effets immunomodulateurs potentiels d'un traitement prolongé par l'oclacitinib chez le chien.. Treize chiens de propriétaires privés atteints de DAC, traités avec 0.4 à 0.6 mg/kg d'oclacitinib pendant 12 mois. MÉTHODES ET MATÉRIELS: Le niveau de prurit a été évalué à l'aide d'une échelle visuelle analogue de prurit (pVAS) et le CADESI IV (Canine Atopic Dermatitis Extent and Severity Index). Des échantillons de sang périphérique ont été prélevés pour des analyses de laboratoire de routine et les sous-types de lymphocytes ont été analysés par cytométrie de flux. La production de cytokines intracellulaires spécifiques de l'antigène à partir des lymphocytes T CD4+ et CD8+ a été analysée après stimulation in vitro par les antigènes de Dermatophagoides farinae. RÉSULTATS: Le traitement par l'oclacitinib a significativement réduit les scores pVAS et CADESI-04, respectivement de 51 % et 86.7 %. L'analyse par cytométrie de flux a révélé une augmentation des populations de lymphocytes CD4+ et CD14+. Le profil des cytokines à 360 jours après le début du traitement était similaire à celui d'avant le traitement et n'était pas associé à une rechute clinique.. L'oclacitinib, lorsqu'il est administré à la dose actuellement marquée pendant un an, est associé à une augmentation significative des cellules T CD4+ circulantes, mais n'altère pas la production de cytokines à partir des cellules T stimulées par l'antigène. Les résultats rapportés ne supportent pas les preuves d'une immunosuppression médiée par les mécanismes évalués dans cette étude.. Die canine atopische Dermatitis (cAD) ist eine chronische Erkrankung, die durch eine Hypersensibilität auf Umweltallergene charakterisiert ist. Oclacitinib maleate verhindert selektiv pro-inflammatorische Mediatoren, die mit cAD im Zusammenhang stehen. Der Einfluss chronischer Verabreichung von Oclacitinib auf die Immunkompetenz muss noch weiter untersucht werden.. In dieser Studie untersuchten wir die möglichen immunmodulatorischen Auswirkungen von verlängerter Behandlung mit Oclacitinib bei Hunden.. Dreizehn Hunde mit cAD in Privatbesitz, die mit 0.4-0.6 mg/kg Oclacitinib 12 Monate lang behandelt worden waren.. Das Juckreizlevel wurde mittels Visual Analog Scale (pVAS) und dem Canine Atopic Dermatitis Extent and Severity Index, 4. Die Behandlung mit Oclacitinib reduzierte die Werte für pVAS und CADESI-04 signifikant um 51% bzw 86.7%. Die Analyse mittels Flowzytometrie zeigte erhöhte CD4. Die Folge einer Oclacitinib Verabreichung für ein Jahr in der zurzeit zugelassenen Dosierung ist eine signifikante Zunahme an zirkulierenden CD4. 背景: 犬アトピー性皮膚炎（cAD）は、環境アレルゲンに対する過敏性を特徴とする慢性疾患である。オクラシチニブマレイン酸塩は、cADに関連する炎症性メディエーターを選択的に阻害する。しかし、オクラシチニブの慢性使用が免疫力に与える影響については、さらなる調査が必要である。 目的: ここでは、犬におけるオクラシチニブの長期投与の潜在的な免疫調節効果を検討した。 被検動物: cADを有するオーナー飼育犬13頭に、0.4～0.6 mg/kgのオクラシチニブを12ヶ月間投与した。 材料と方法: 痒みレベルは、痒みのVisual Analog Scale（pVAS）およびCanine atopic dermatitis extent and severity index, 4. A dermatite atópica canina (DAC) é uma doença crônica caracterizada por hipersensibilidade a alérgenos ambientais. O maleato de oclacitinib inibe seletivamente mediadores pró-inflamatórios associados à DAC. Entretanto, o impacto do uso crônico de oclacitinib na imunocompetência requer mais estudos.. Neste estudo, nós avaliamos os efeitos imunomodulatórios potenciais do uso prolongado de oclacitinib em cães.. Treze cães de proprietários com DAC, tratados com 0.4-0.6 mg/kg de oclacitinib por 12 meses. MÉTODOS E MATERIAIS: O grau de prurido foi avaliado utilizando a escala analógica visual de prurido (pVAS) e o índice de gravidade e extensão da dermatite atópica canina, 4ª iteração (CADESI IV). Amostras de sangue periférico foram coletadas por ensaios laboratoriais de rotina e os subtipos de linfócitos foram analisados utilizando citometria de fluxo. A produção de citocinas antígeno-específicas intracelulares de linfócitos T CD4+ e TCD8+ foi analisada após estimulação in vitro com antígenos de Dermatophagoides farinae.. O tratamento com oclacitinib reduziu significativamente os escores pVAS e CADESI-04 em 51% e 86.7%, respectivamente. A análise por citometria de fluxo revelou aumento nas populações de linfócitos T CD4+ e T CD8+. O perfil de citocinas após 360 dias do início do tratamento foi similar àquele de antes do tratamento e não foi associado à recidiva clínica. CONCLUSÃO: A administração de oclacitinib na dose proposta pelo fabricante durante um ano é associada a um aumento significativo das células T CD4+ circulantes, mas não alterou a produção de citocinas pelas células T estimuladas por antígenos. Estes resultados não suportam evidências de imunossupressão mediada pelos mecanismos avaliados no estudo.. INTRODUCCIÓN: la dermatitis atópica canina (cAD) es una enfermedad crónica caracterizada por hipersensibilidad a los alérgenos ambientales. El maleato de oclacitinib inhibe selectivamente los mediadores proinflamatorios asociados con la cAD. Sin embargo, el impacto del uso crónico de oclacitinib en la inmunocompetencia requiere más investigación. OBJETIVOS: en este documento, examinamos los posibles efectos inmunomoduladores del tratamiento prolongado con oclacitinib en perros. ANIMALES: trece perros de propiedad privada con cAD, tratados con 0.4 a 0.6 mg/kg de oclacitinib durante 12 meses. MÉTODOS Y MATERIALES: el nivel de prurito se evaluó mediante una escala análoga visual de prurito (pVAS) y el índice de extensión y gravedad de la dermatitis atópica canina, cuarta revisión (CADESI IV). Se recolectaron muestras de sangre periférica para ensayos de laboratorio de rutina y se analizaron los subtipos de linfocitos mediante citometría de flujo. Se analizó la producción de citoquinas intracelulares específicas de antígeno a partir de linfocitos T CD4 + y CD8 + después de la estimulación in vitro por antígenos de Dermatophagoides farinae. RESULTADOS: el tratamiento con oclacitinib redujo significativamente los valores de pVAS y CADESI-04, en un 51% y un 86.7%, respectivamente. El análisis de citometría de flujo reveló un aumento de las poblaciones de linfocitos CD4 + y CD14 +. El perfil de citocinas a los 360 días después del inicio del tratamiento fue similar al anterior al tratamiento y no se asoció con una recaída clínica. CONCLUSIÓN: Oclacitinib, cuando se administra a la dosis actualmente etiquetada durante un año, se asocia con un aumento significativo de las células T CD4 + circulantes, pero no altera la producción de citoquinas a partir de las células T estimuladas por antígenos. Los resultados obtenidos no apoyan la evidencia de inmunosupresión mediada por los mecanismos evaluados en este estudio.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Maleates; Pyrimidines; Sulfonamides

Oclacitinib administered at the licensed dose twice daily for two weeks and then once daily as required is recommended for the treatment of atopic dogs. In some cases, the once-daily regimen is insufficient to control the clinical signs.. To provide preliminary safety and efficacy data on the prolonged twice-daily administration of oclacitinib in atopic dogs.. Fifty-three client-owned atopic dogs.. The medical records of dogs with atopic dermatitis treated with oclacitinib twice daily for more than two weeks were reviewed retrospectively. Animal details, treatment dose and duration, concurrent diseases, adjunctive medications and possible adverse events were recorded. Treatment efficacy was assessed retrospectively and, when available, the selected blood parameters before and during the treatment were compared. Statistical analyses of the collected data were performed.. The median treatment duration was 113 days. Excellent-to-good efficacy was observed in 38 dogs (72%), including 24 of 33 dogs that failed to respond to the once-daily regimen. Eight dogs showed a poor response despite the addition of systemic glucocorticoids. Pyoderma, gastrointestinal signs and otitis externa were the most frequent adverse events recorded whilst on treatment. Blood tests performed in 35 dogs showed slightly decreased leucocyte, neutrophil, eosinophil and monocyte counts that remained within the reference ranges in most cases. Three dogs developed hypercholesterolemia.. Prolonged twice-daily administration of oclacitinib generally was well-tolerated and was effective in most of the treated dogs. Regular clinical evaluation and blood tests are advisable for this treatment regimen.. L'oclacitinib administré à la dose autorisée deux fois par jour pendant deux semaines puis une fois par jour selon les besoins est recommandé pour le traitement des chiens atopiques. Dans certains cas, le régime à prise unique quotidienne est insuffisant pour contrôler les signes cliniques.. Fournir des données préliminaires d'innocuité et d'efficacité sur l'administration biquotidienne prolongée d'oclacitinib chez les chiens atopiques.. Cinquante-trois chiens atopiques appartenant à des clients. MATÉRIELS ET MÉTHODES: Les dossiers médicaux des chiens atteints de dermatite atopique traités par oclacitinib deux fois par jour pendant plus de deux semaines ont été revus rétrospectivement. Les détails sur les animaux, la dose et la durée du traitement, les maladies concomitantes, les médicaments d'appoint et les événements indésirables possibles ont été enregistrés. L'efficacité du traitement a été évaluée rétrospectivement et, lorsqu'ils étaient disponibles, les paramètres sanguins sélectionnés avant et pendant le traitement ont été comparés. Des analyses statistiques des données recueillies ont été effectuées. RÉSULTATS: La durée médiane de traitement était de 113 jours. Une efficacité excellente à bonne a été observée chez 38 chiens (72 %), dont 24 des 33 chiens qui n'ont pas répondu au régime à prise unique quotidienne. Huit chiens ont montré une mauvaise réponse malgré l'ajout de corticoïdes systémiques. La pyodermite, les signes gastro-intestinaux et l'otite externe ont été les événements indésirables les plus fréquemment enregistrés pendant le traitement. Des tests sanguins effectués chez 35 chiens ont montré une légère diminution des numérations de leucocytes, de neutrophiles, d'éosinophiles et de monocytes qui sont restées dans les plages de référence dans la plupart des cas. Trois chiens ont développé une hypercholestérolémie.. L'administration prolongée d'oclacitinib deux fois par jour a généralement été bien tolérée et a été efficace chez la plupart des chiens traités. Une évaluation clinique régulière et des tests sanguins sont recommandés pour ce régime de traitement.. INTRODUCCIÓN: se recomienda la administración de oclacitinib a la dosis autorizada dos veces al día durante dos semanas y luego una vez al día, según sea necesario, para el tratamiento de perros atópicos. En algunos casos, el régimen de una vez al día es insuficiente para controlar los signos clínicos. OBJETIVOS: proporcionar datos preliminares de seguridad y eficacia durante la administración prolongada dos veces al día de oclacitinib en perros atópicos. ANIMALES: cincuenta y tres perros atópicos de propietarios particulares. MÉTODOS Y MATERIALES: se revisaron retrospectivamente los historiales médicos de perros con dermatitis atópica tratados con oclacitinib dos veces al día durante más de dos semanas. Se registraron los detalles de los animales, la dosis y la duración del tratamiento, las enfermedades concurrentes, los medicamentos complementarios y los posibles eventos adversos. La eficacia del tratamiento se evaluó retrospectivamente y, cuando estuvieron disponibles, se compararon los parámetros sanguíneos seleccionados antes y durante el tratamiento. Se realizaron análisis estadísticos de los datos recopilados. RESULTADOS: la duración media del tratamiento fue de 113 días. Se observó una eficacia de excelente a buena en 38 perros (72%), incluidos 24 de 33 perros que no respondieron al régimen de una vez al día. Ocho perros mostraron una mala respuesta a pesar de la adición de glucocorticoides sistémicos. Pioderma, signos gastrointestinales y otitis externa fueron los eventos adversos más frecuentes observados durante el tratamiento. Los análisis de sangre realizados en 35 perros mostraron recuentos de leucocitos, neutrófilos, eosinófilos y monocitos ligeramente disminuidos que permanecieron dentro de los rangos de referencia en la mayoría de los casos. Tres perros desarrollaron hipercolesterolemia. CONCLUSIONES Y RELEVANCIA CLÍNICA: la administración prolongada dos veces al día de oclacitinib fue generalmente bien tolerada y eficaz en la mayoría de los perros tratados. Se recomiendan evaluaciones clínicas y análisis de sangre regulares para este régimen de tratamiento.. Oclacitinib wird für die Behandlung von atopischen Hunden bei der zugelassenen Dosis zweimal täglich zwei Wochen lang und danach einmal täglich empfohlen. Bei einigen Fällen ist die einmal tägliche Anwendung zur Kontrolle der klinischen Zeichen zu wenig.. Eine Vorlage der vorläufigen Sicherheits- und Wirksamkeitsdaten der verlängerten zweimal täglichen Verabreichung von Oclacitinib bei atopischen Hunden.. Dreiundfünfzig atopische Hunde in Privatbesitz.. Die medizinischen Daten von Hunden mit atopischer Dermatitis, die zweimal täglich mehr als zwei Wochen lang behandelt worden waren, wurden retrospektiv reviewed. Details der Tiere, Behandlungsdosis und -dauer, Vorerkrankungen, zusätzliche Medikationen und mögliche Nebenwirkungen wurden festgehalten. Die Wirksamkeit der Behandlung wurde retrospektiv erfasst und wenn verfügbar, wurden die ausgewählten Blutparameter vor und nach der Behandlung verglichen. Mit den gesammelten Daten wurde eine statistische Analyse durchgeführt.. Die mediane Behandlungsdauer betrug 113 Tage. Ausgezeichnete-bis-gute Wirksamkeit wurde bei 38 Hunden (72%), inklusive 24 der 33 Hunde, die auf die einmal tägliche Verabreichung nicht ausreichend reagiert hatten, beobachtet. Acht Hunde zeigten eine ungenügende Besserung trotz der zusätzlichen Gabe von systemischen Glucocorticoiden. Pyoderma, gastrointestinale Zeichen und Otitis externa waren die am häufigsten beschriebenen Nebenwirkungen während der Behandlung. Blutuntersuchungen, die bei 35 Hunden durchgeführt wurden, zeigten geringgradig erhöhte Leukozyten, Neutrophile, Eosinophile und Monozytenzahlen, die bei den meisten Fällen innerhalb der Referenzwerte blieben. Drei Hunde entwickelten eine Hypercholesterolämie.. Eine verlängerte zweimal tägliche Verabreichung von Oclacitinib wurde generell gut toleriert und war bei den meisten der behandelten Hunde wirksam. Eine regelmäßige klinische Evaluierung und Bluttests sind bei diesem Behandlungsschema empfohlen.. 背景: アトピー犬の治療には、オクラシチニブの1日2回投与で2週間、その後必要に応じて1日1回の投与が推奨されている。しかし、1日1回の投与では臨床症状を抑えることができない場合がある。 目的: 本研究の目的は、アトピー犬におけるオクラシチニブの1日2回の長期投与に関する安全性および有効性の予備的データを提供することであった。 供試動物: オーナー所有アトピー犬 53 頭。 材料と方法: オクラシチニブを 1 日 2 回、2 週間以上投与したアトピー性皮膚炎の犬のカルテを回顧的に検討した。動物の詳細、治療量および期間、併発疾患、補助薬、起こりうる有害事象を記録した。治療効果を回顧的に評価し、可能であれば、治療前および治療中の選択された血液パラメータを比較した。収集されたデータの統計解析を実施した。 結果: 治療期間の中央値は113日であった。1日1回投与で無効となった33頭中24頭を含む38頭(72%)で有効性が確認され、良好であった。また，全身性グルココルチコイド製剤を追加したにもかかわらず，効果が不十分であった犬は8頭であった。有害事象は，膿皮症，消化器症状および外耳炎が主なものであり，1日1回投与では，膿皮症，消化器症状および外耳炎は認められなかった.血液検査では、35頭の犬で白血球、好中球、好酸球、単球の数がわずかに減少したが、ほとんどの症例で基準範囲内にとどまった。また、3頭の犬に高コレステロール血症が認められた。 結論と臨床的意義: オクラシチニブの1日2回の長期投与は概して忍容性が高く、ほとんどの治療犬で有効であった。この治療法では、定期的な臨床評価および血液検査が望まれる。.. 背景: 建议以获批剂量给予奥拉替尼，每日两次，持续两周，然后根据需要每日一次，用于治疗特应性犬。在某些情况下，每日一次给药方案不足以控制临床症状。 目的: 提供特应性犬长期每日两次给予奥拉替尼的初步安全性和有效性数据。 动物: 53只私家特应性患犬。 方法和材料-回顾性审查接受奥拉替尼每日两次治疗，超过两周的特应性皮炎犬的病历。记录动物详情、给药剂量和持续时间、并发疾病、辅助药物和可能的副反应。回顾性评估治疗疗效，如果可能的话，比较治疗前和治疗期间选定的血液指标。对收集的数据进行统计分析。 结果: 中位治疗持续时间为113天。在38只犬(72%)中观察到极佳至良好的有效性，包括每日一次方案治疗无效的24/33只犬。尽管加用了全身性糖皮质激素，但8只犬的反应较差。脓皮病、胃肠道症状和外耳炎是治疗期间记录的最常见副反应。在35只犬中进行的血液检查显示白细胞、中性粒细胞、嗜酸性粒细胞和单核细胞计数轻微降低，在大多数情况下保持在参考范围内。3只犬出现高胆固醇血症。 结论和临床相关性: 奥拉替尼长期每日两次给药通常耐受良好，在大多数给药犬中有效。建议对该治疗方案进行定期临床评价和血液检查。.. O oclacitinib administrado na dose autorizada duas vezes ao dia durante duas semanas e, em seguida, uma vez ao dia conforme necessidade, é recomendado no tratamento de cães atópicos. Em alguns casos, o regime de uma vez ao dia é insuficiente para controlar os sinais clínicos.. Fornecer dados preliminares sobre segurança e eficácia da administração prolongada de oclacitinib duas vezes ao dia em cães atópicos.. Cinquenta e três cães atópicos pertencentes a clientes. MÉTODOS E MATERIAIS: Os prontuários de cães com dermatite atópica tratados com oclacitinib duas vezes ao dia por mais de duas semanas foram revisados retrospectivamente. Detalhes dos animais, dose e duração do tratamento, doenças concomitantes, medicamentos adjuvantes e possíveis eventos adversos foram registrados. A eficácia do tratamento foi avaliada retrospectivamente e, quando disponíveis, parâmetros sanguíneos selecionados antes e durante o tratamento foram comparados. Foram realizadas análises estatísticas dos dados coletados.. A duração média do tratamento foi de 113 dias. Eficácia boa a excelente foi observada em 38 cães (72%), incluindo 24 de 33 cães que não responderam ao regime de uma vez ao dia. Oito cães mostraram uma resposta pobre, apesar da adição de glicocorticóides sistêmicos. Piodermite, sinais gastrointestinais e otite externa foram os eventos adversos mais frequentes registrados durante o tratamento. Os exames de sangue realizados em 35 cães demonstraram contagens de leucócitos, neutrófilos, eosinófilos e monócitos discretamente diminuídas, que permaneceram dentro dos intervalos de referência na maioria dos casos. Três cães desenvolveram hipercolesterolemia. CONCLUSÕES E RELEVÂNCIA CLÍNICA: A administração prolongada de oclacitinib duas vezes ao dia foi geralmente bem tolerada e eficaz na maioria dos cães tratados. Avaliação clínica regular e exames de sangue são recomendados para este regime de tratamento.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Pyrimidines; Retrospective Studies; Sulfonamides

The oral acceptance of oclacitinib maleate (Apoquel®) chewable tablets administered twice daily for 7 days at the labeled dose range of 0.4-0.6 mg/kg was evaluated in 121 dogs treated at ten general practice veterinary clinics in the United States.. Dogs that were enrolled in the study were client-owned, ranged from 1 to 14 years of age, weighed 3.7 to 60.7 kg, and required twice daily treatment with Apoquel for allergic or atopic dermatitis for 7 days. One hundred and twenty-one (121) dogs with 1673 total dose administrations successfully completed the study and were included in the data summary. Out of a total number of 1673 administrations, 1533 (91.6%) were accepted voluntarily within 5 min, 134 (8%) were consumed with assistance (with food treats or by pilling) outside of the 5 min offering time and 6 (0.4%) doses were not consumed. The per dose percent acceptance rate for the 14 offered doses showed minimal variation ranging from 89.9 to 93.3%.. Client-owned dogs from the general veterinary patient population that required treatment with oclacitinib found the chewable tablets to be very palatable and no aversion occurred with repeated dosing. Oclacitinib chewable tablets were well tolerated and are a palatable alternative to the film-coated tablet.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Maleates; Pyrimidines; Sulfonamides; Tablets; United States

Canine allergic dermatitis is a common diagnosis in veterinary practices which can lead to secondary infections requiring treatment with antimicrobials. A previous study suggested that dogs treated with oclacitinib in an Australian referral hospital required fewer courses of antimicrobial therapy compared to dogs receiving other anti-pruritic treatments. This study aimed to quantify the effect of oclacitinib treatment on the use of antimicrobials and other therapies in general practice veterinary clinics across Australia. A retrospective case-controlled review of patient records was designed to investigate the number of courses of antimicrobials and other therapies in dogs that received oclacitinib (Apoquel®), compared with those who received an anti-pruritic treatment that was not oclacitinib.. The target population included canine patients with a presumptive diagnosis of allergic dermatitis presenting between 2008 and 2018 to general practices contributing to the VetCompass Australia database. Patient records of interest were identified using search terms relating to allergic dermatitis, resulting in over 700,000 observations. Multivariable logistic regression models were developed to determine whether cases were prescribed fewer antimicrobial courses than controls, after adjusting for the presence of concurrent skin infections or infectious agents in ears. Our results indicate that fewer antimicrobial courses were prescribed in the cases compared to the controls. After adjusting for the concurrent skin infections, there was a significant reduction in the use of cefovecin [OR:0.62(0.39-0.98), P = 0.043], chlorhexidine [OR:0.57(0.42-0.77), P < 0.001], neomycin [OR:0.4(0.28-0.56), P < 0.001] and amoxycillin clavulanic acid (AMC) [OR: 0.55(0.39-0.78), P = 0.001] in cases compared to controls.. This study demonstrates a potential sparing effect of oclacitinib on the prescription of antimicrobials for the treatment of allergic skin diseases in dogs. This information may assist in the planning of treatment for canine allergic dermatitis, with consideration for antimicrobial stewardship.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Australia; Case-Control Studies; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Hypersensitivity; Pyrimidines; Retrospective Studies; Sulfonamides

Toxoplasma gondii is a ubiquitous protozoan, for which felids are the definitive host. Immunocompromised individuals are susceptible to recrudescent toxoplasmosis. This case describes a 6-year-old, feline immunodeficiency virus-positive domestic short hair cat with feline atopic skin syndrome that developed fatal toxoplasmosis after treatment with oclacitinib for five months.. Toxoplasma gondii est un protozoaire ubiquitaire dont les félidés sont l'hôte définitif. Les personnes immunodéprimées sont sensibles à la toxoplasmose recrudescente. Ce cas décrit un chat domestique à poils courts de 6 ans, positif pour le virus de l'immunodéficience féline, atteint du syndrome atopique cutané félin, qui a développé une toxoplasmose mortelle après un traitement à l'oclacitinib pendant cinq mois.. Toxoplasma gondii es un protozoo ubicuo, cuyo huésped definitivo son los felinos. Las personas inmunocomprometidas son susceptibles a la toxoplasmosis recrudescente. Este caso describe un gato doméstico de pelo corto positivo para el virus de la inmunodeficiencia felina de 6 años de edad con síndrome de piel atópica felina, que desarrolló toxoplasmosis fatal después del tratamiento con oclacitinib durante cinco meses.. Toxoplasma gondii ist ein ubiquitäres Protozoon, für welches Felidae den definitiven Wirt darstellen. Immunkompromitierte Individuen sind empfänglich für eine sich verschlimmernde Toxoplasmose. Dieser Fall beschreibt eine 6 Jahre alte Hauskatze, die auf das Feline Immunodefizienz Virus positiv getestet war und am felinen atopischen Hautsyndrom litt, welche nach einer 5 monatigen Behandlung mit Oclacitinib eine fatale Toxoplasmose entwickelte.. Toxoplasma gondiiは，ネコ科動物を宿主とする至る所にある原虫である。免疫不全を起こしていると再発性トキソプラズマ症に罹患しやすい。本症例は、猫アトピー性皮膚症候群の猫免疫不全ウイルス陽性ドメスティック・ショート・ヘアー(6歳)が、オクラシチニブによる5カ月間の治療後に致死的なトキソプラズマ症を発症したものである。.. 弓形虫是一种普遍存在的原虫，猫科动物是其终末宿主。免疫功能低下者易患复发性弓形虫病。该病例描述了1只患有猫特应性皮肤综合征的6岁家养短毛猫，猫免疫缺陷病毒阳性，在接受奥拉替尼治疗5个月后发生致死性弓形虫病。.. Toxoplasma gondii é um protozoário ubíquo para o qual os felídeos são o hospedeiro definitivo. Indivíduos imunocomprometidos são suscetíveis a toxoplasmose recrudescente. Este relato descreve um caso de um felino doméstico de pelo curto de seis anos de idade, positivo para o vírus da imunodeficiência felina, com síndrome atópica felina, que desenvolveu toxoplasmose fatal após tratamento com oclacitinib por cinco meses.

Topics: Animals; Cat Diseases; Cats; Dermatitis, Atopic; Immunodeficiency Virus, Feline; Pyrimidines; Sulfonamides; Toxoplasma; Toxoplasmosis, Animal

Murine ulcerative dermatitis (UD) is a common, multifactorial skin disease of C57BL/6 and C57BL/6-background strains of mice. Many treatment options have been previously reported but have been variably successful and may interfere with specific research studies. Janus kinase (JAK) inhibitors, such as oclacitinib, have been used to treat allergic dermatitis in humans, dogs, and other species. Additionally, topical oclacitinib was shown to improve an induced model of dermatitis in mice. We hypothesized that topical application of oclacitinib in conjunction with hind limb nail trimming would improve UD lesion scores more than our institutional standard treatment regime using meloxicam, topical antibiotic ointment, and nail trimming or nail trimming alone. To test this, mice with naturally occurring UD were recruited to the study and assigned to one of three treatment groups (n = 14/group): nail trim only; nail trim plus meloxicam and topical triple antibiotic ointment; or nail trim plus topical oclacitinib. UD was assessed on days 1, 7, and 14 for all treatment groups, and scored based on a previously published scoring system that quantitatively scored UD lesions based on pruritus, character of the lesion, size of lesion, and location of lesion. Here we found that mean UD scores decreased from day 1 to day 7 and from day 1 to day 14 for all treatment groups. However, there was no significant difference in mean UD score between the treatment groups at any timepoint. These data show that topical oclacitinib and nail trimming together improved UD lesion scores comparably to our institutional standard treatment and nail trimming alone. However, further studies may be warranted to investigate other potential applications of oclacitinib to treat UD.

Topics: Animals; Anti-Bacterial Agents; Dermatitis, Atopic; Dogs; Humans; Janus Kinases; Meloxicam; Mice; Mice, Inbred C57BL; Ointments; Skin Ulcer

Ear tip ulcerative dermatitis (ETUD) is an uncommon clinical reaction pattern in canine dermatology. The lesions are suggestive of vascular damage which may be caused by inflammatory or noninflammatory diseases, and often are idiopathic. Therapeutic options for ETUD include topical glucocorticoids or tacrolimus, pentoxifylline, vitamin E, doxycycline, tetracycline and niacinamide, sulfonamides, glucocorticoids, ciclosporin and surgical correction.. The aims of this retrospective case series were to describe the clinical features and report response to treatment with oclacitinib in dogs with idiopathic, chronic ETUD.. Twenty-five privately owned dogs with unilateral or bilateral ETUD.. Cases of ETUD which were poorly responsive to conventional therapy and subsequently treated with oclacitinib, are summarised. All cases were tested for leishmaniosis by serological examination [indirect fluorescent antibody test (IFAT) or enzyme-linked immunosorbent assay (ELISA)]. Histopathological examination was performed in two cases.. Serological results were negative for leishmaniosis in all dogs. Histopathological changes consistent with proliferative thrombovascular necrosis of the pinnae were documented in two cases. Oclacitinib, used at the standard dose range recommended for the treatment of canine atopic dermatitis, effectively resolved ETUD in 22 of 25 dogs within one to three months. Several of the dogs required prolonged use of twice daily dosing.. Oclacitinib should be included among the therapeutic options for ETUD, once infectious diseases have been ruled out.. L'ETUD (Ear Tip Ulcerative Dermatitis) est un patron réactionnel clinique rare en dermatologie canine. Les lésions sont suggestives d'un dommage vasculaire qui peut être causé par des maladies inflammatoires ou non inflammatoires, souvent idiopathiques. Les options thérapeutiques pour ETUD comprennent les corticoïdes topiques, le tacrolimus, la pentoxifylline, la vitamine E, la doxycycline, la tétracycline et niacinamide, les sulfonamides, les corticoïdes, la ciclosporine et la chirurgie. HYPOTHÈSES/OBJECTIFS: Les buts de cette série rétrospective de cas étaient de décrire les données cliniques et rapporter les réponses aux traitements avec l’oclacitinib chez les chiens avec ETUD chronique idiopathique.. Vingt-cinq chiens de propriétaire avec ETUD unilatérale ou bilatérale. MATÉRIELS ET MÉTHODES: Les cas d’ETUD qui répondaient mal au traitement conventionnel et ainsi traités avec de l’oclacitinib, ont été résumés. Tous les cas ont été testés pour leishmaniose par examen sérologique [indirect fluorescent antibody test (IFAT) ou enzyme-linked immunosorbent assay (ELISA)]. L’examen histopathologique a été réalisé pour deux cas. RÉSULTATS: Les résultats sérologiques étaient négatifs pour la leishmaniose pour tous les chiens. Les changements histopathologiques consistaient en une nécrose thrombovasculaire proliférative des pavillons, documentés dans deux cas. L’oclacitinib, utilisé à la dose standard recommandée pour le traitement de la dermatite atopique canine, a été efficace pour 22 des 25 chiens en un à trois mois. Plusieurs des chiens ont nécessité un traitement prolongé d’une dose deux fois par jour.. L’oclacitinib devrait être incluse dans les options thérapeutiques de l’ETUD, lorsque les infections ont été éliminées.. INTRODUCCIÓN: la dermatitis ulcerativa de la punta del oído (ETUD) es un patrón de reacción clínica poco común en la dermatología canina. Las lesiones sugieren daño vascular que puede ser causado por enfermedades inflamatorias o no inflamatorias y, a menudo, son idiopáticas. Las opciones terapéuticas para ETUD incluyen glucocorticoides tópicos o tacrolimus, pentoxifilina, vitamina E, doxiciclina, tetraciclina y niacinamida, sulfonamidas, glucocorticoides, ciclosporina y corrección quirúrgica. HIPÓTESIS/OBJETIVOS: los objetivos de esta serie de casos retrospectivos fueron describir las características clínicas e informar de la respuesta al tratamiento con oclacitinib en perros con ETUD crónica idiopática. ANIMALES: veinticinco perros de propietarios particulares con ETUD unilateral o bilateral. MÉTODOS Y MATERIALES: se resumen los casos de ETUD que respondieron mal a la terapia convencional y posteriormente se trataron con oclacitinib. Todos los casos se analizaron para detectar leishmaniosis mediante examen serológico [prueba de anticuerpos fluorescentes indirecta (IFAT) o ensayo inmunoabsorbente ligado a enzimas (ELISA)]. Se realizó examen histopatológico en dos casos. RESULTADOS: los resultados serológicos fueron negativos para leishmaniosis en todos los perros. En dos casos se documentaron cambios histopatológicos compatibles con necrosis trombovascular proliferativa del pabellón auricular. Oclacitinib, utilizado en el rango de dosis estándar recomendado para el tratamiento de la dermatitis atópica canina, resolvió eficazmente la ETUD en 22 de 25 perros en uno a tres meses. Varios de los perros requirieron el uso prolongado de dosis dos veces al día. CONCLUSIÓN Y RELEVANCIA CLÍNICA: El oclacitinib debe incluirse entre las opciones terapéuticas para la ETUD, una vez descartadas enfermedades infecciosas.. Bei der ulzerativen Ohrranddermatitis (ETUD) handelt es sich um ein seltenes klinisches Reaktionsmuster in der Dermatologie des Hundes. Die Läsionen weisen auf Blutgefäßschädigungen hin, die durch entzündliche oder nicht entzündliche Erkrankungen verursacht werden können, oft aber auch idiopathisch auftreten.. Die Ziele dieser retrospektiven Fallserie waren die Beschreibung der klinischen Merkmale und ein Bericht über das Ansprechen auf eine Behandlung mit Oclacitinib bei Hunden mit idiopathischer, chronischer ETUD.. Fünfundzwanzig Hunde in Privatbesitz mit uni- oder bilateraler ETUD.. Fälle von ETUD, die auf eine konventionelle Therapie nur schlecht ansprachen und in der Folge mit Oclacitinib behandelt wurden, sind zusammengefasst. Alle Fälle wurden mittels serologischer Untersuchung [Indirekter Immuno Fluoreszenz Antikörpertest (IFAT) oder Enzym-Linked Immunosorbent Assay (ELISA)] auf Leishmaniose getestet. In zwei Fällen wurde eine histopathologische Untersuchung durchgeführt.. Die serologischen Ergebnisse waren bei allen Hunden negativ für Leishmaniose. In zwei Fällen wurden histopathologische Veränderungen passend zu einer proliferativen thrombovaskulären Nekrose der Pinnae dokumentiert. Bei 22 von 25 Hunden konnte mittels Oclacitinib, welches in der empfohlenen Standarddosis zur Behandlung einer atopischen Dermatitis des Hundes eingesetzt wurde, innerhalb von einem bis drei Monaten die ETUD erfolgreich behandelt werden. Einige der Hunde benötigten langfristig eine zweimal tägliche Dosierung.. Wenn infektiöse Erkrankungen ausgeschlossen wurden, sollte Oclacitinib in die therapeutischen Optionen für ETUD inkludiert werden.. 背景: 耳介先端部潰瘍性皮膚炎（ETUD）は、犬の皮膚科では珍しい臨床反応パターンである。炎症性疾患や非炎症性疾患による血管障害を示唆する病変であり、特発性のものも多い。ETUDの治療法としては、グルココルチコイドやタクロリムスの外用、ペントキシフィリン、ビタミンE、ドキシサイクリン、テトラサイクリン、ナイアシンアミド、スルホンアミド、グルココルチコイド、シクロスポリン、外科的矯正などがある。 仮説／目的: この回顧的な症例シリーズの目的は、特発性の慢性ETUDを持つ犬の臨床的特徴を説明し、オクラシチニブによる治療に対する反応を報告することであった。 被験動物: 片側または両側のETUDを有する25頭のオーナー所有犬。 材料と方法: 従来の治療に反応が悪く、その後オクラシチニブで治療したETUDの症例をまとめている。全例、血清学的検査［間接蛍光抗体法（IFAT）または酵素結合免疫吸着法（ELISA）］によりリーシュマニア症の検査を行った。また，2例では病理組織学的検査を行った。 結果: 血清検査の結果、すべての犬でリーシュマニア症は陰性であった。耳介の増殖性血栓性血管性壊死と一致する病理組織学的変化が2例で記録された。オクラシチニブは、犬アトピー性皮膚炎治療に推奨される標準的な用量範囲で使用され、25頭中22頭のETUDを1～3か月以内に効果的に解決した。数頭の犬は、1日2回の投与を長期に渡って行う必要があった。 結論と臨床的妥当性: オクラシチニブは、感染症が除外された後、ETUDの治療オプションに含まれるべきである。.. 背景: 耳尖溃疡性皮炎(ETUD)是犬皮肤病学中不常见的临床反应模式。病变提示血管损伤，可能由炎性或非炎性疾病引起，通常为特发性。ETUD的治疗选择包括外用糖皮质激素或他克莫司、己酮可可碱、维生素E、多西环素、四环素和烟酰胺、磺胺类药物、糖皮质激素、环孢素和手术矫正。 假设/目的: 本回顾性病例系列的目的是描述特发性、慢性ETUD犬的临床特征，并报告对奥拉替尼治疗的反应。 动物: 25只患有单侧或双侧ETUD的私家犬。 方法和材料: 总结了对常规治疗反应不佳且随后接受奥拉替尼治疗的ETUD病例。所有病例均经血清学检查[间接荧光抗体试验(IFAT)或酶联免疫吸附试验(ELISA)]检测利什曼病。2例进行了组织病理学检查。 结果: 所有犬的利什曼病血清学结果均为阴性。2例组织病理学变化记录为耳廓增生性血栓血管坏死。奥拉替尼使用按照治疗犬特应性皮炎的标准推荐剂量范围，在1-3个月内，22/25只ETUD患犬得到有效缓解。一些犬需要长期使用，且每日两次给药。 结论和临床相关性: 一旦排除感染性疾病，应将奥拉替尼纳入ETUD的治疗备选方案。.. A dermatite ulcerativa da borda da orelha (DUBO) é um padrão reacional incomum na dermatologia canina. As lesões são sugestivas de dano vascular, que pode ser causado por doenças inflamatórias ou não inflamatórias, e frequentemente são idiopáticas. As opções terapêuticas para a DUBO incluem glicocorticoides tópicos ou tacrolimus, pentoxifilina, vitamina E, doxiciclina, tetraciclina e niacinamida, sulfonamidas, glicocorticoides e correção cirúrgica. HIPÓTESE/OBJETIVOS: O objetivo dessa série de casos retrospectivos foi descrever as características clínicas e relatar a resposta de cães com DUBO crônica idiopática ao tratamento com oclacitinib.. Vinte e cinco cães de propriedade privada com DUBO unilateral ou bilateral. MÉTODOS E MATERIAIS: Os casos de DUBO que apresentaram resposta insatisfatória à terapia convencional e foram subsequentemente tratados com oclacitinib foram descritos neste trabalho. Todos os casos foram testados para leishmaniose por exame sorológico [método de indirect fluorescent antibody test (IFAT) ou de enzyme-linked immunosorbent assay (ELISA)]. Dois casos foram enviados para exame histopatológico.. Os testes sorológicos foram negativos para leishmaniose em todos os cães. Achados histopatológicos compatíveis com necrose trombovascular proliferativa do pavilhão auricular foram observados em dois casos. O oclacitinib, utilizado na dose recomendada para o tratamento de dermatite atópica canina, resolveu efetivamente a DUBO em 22 dos 25 casos em um período de um a três meses. Muitos cães necessitaram de tratamento prolongado com a dose de duas vezes ao dia. CONCLUSÃO E RELEVÂNCIA CLÍNICA: O oclacitinib deve ser incluso nas opções terapêuticas para DUBO quando as causas infecciosas forem excluídas.

Topics: Animals; Dermatitis, Atopic; Dog Diseases; Dogs; Pyrimidines; Retrospective Studies; Skin Ulcer; Sulfonamides

Oclacitinib is a Janus kinase (JK)1 inhibitor that has been shown to be effective and safe for the treatment of allergic dermatitis in dogs. Its use in cats has been limited by the absence of pharmacokinetic data.. To determine the pharmacokinetic parameters of oclacitinib in cats after oral and intravenous administration.. Six adult domestic short hair cats.. A two period, two treatment design was used in which cats received oclacitinib maleate i.v. and p.o., at a dose of 0.5 mg/kg and 1 mg/kg, respectively. There was a one-week interval of washout between the two treatments. Cats received each treatment only once. The plasma concentration of oclacitinib was determined by high-performance liquid chromatography at 0 min, 5 min, 15 min, 30 min, 1 h, 4 h, 6 h, 10 h and 24 h after intravenous.v administration, at 0 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 10 h and 24 h after p.o. administration.. The pharmacokinetic parameters of oclacitinib in the cat are similar to those described for the dog, although absorption and elimination are somewhat faster and variability between individuals is somewhat greater. Larger doses and/or shorter dosing intervals would be recommended in cats to achieve similar blood concentrations to those in dogs.. L'oclacitinib est un inhibiteur de Janus Kinase (JK)1 qui a montré son efficacité et son innocuité dans le traitement de la dermatite allergique canine. Son utilisation chez le chat est limitée par l'absence de données pharmacocinétiques.. Déterminer les paramètres pharmacocinétiques de l'oclacitinib chez le chat après administration orale et intraveineuse.. Les paramètres pharmacocinétiques de l'oclacitinib chez le chat sont semblables à ceux décrits chez le chien bien que l'absorption et l’élimination soient quelque peu plus rapides et la variabilité entre les individus est quelque peu plus importante. Les doses plus importantes et/ou les intervalles de dosage pourraient être recommandés chez le chat pour atteindre les concentrations sanguines semblables à celles du chien.. Oclacitinib ist ein Janus Kinase (JK)1 Inhibitor, der sich als wirksam und sicher bei der Behandlung der allergischen Dermatitis von Hunden gezeigt hat. Seine Verwendung bei Katzen ist aufgrund der fehlenden pharmakokinetischen Daten limitiert. ZIEL: Eine Bestimmung der pharmakokinetischen Parameter von Oclacitinib bei Katzen nach einer intravenösen Administration oder einer Administration per os.. Sechs erwachsene domestizierte Kurzhaarkatzen.. Ein Design mit zwei Perioden und zwei Behandlungen wurde angewendet, in welchem die Katzen Oclacitinib Maleate i.v. und p.o. bei einer Dosierung von 0,5 mg/kg bzw 1 mg/kg erhielten. Es bestand ein Washout Intervall von einer Woche zwischen den beiden Behandlungen. Die Katzen erhielten jede Behandlung nur einmal. Die Plasmakonzentration von Oclacitinib wurde mittels Hochperformance Liquidchromatografie zum Zeitpunkt 0 min, 15 min, 30 min, 1 h, 4 h, 6 h, 10 h und 24 h nach der intravenösen Administration sowie zum Zeitpunkt 0 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 10 h und 24 h nach der Administration p.o. bestimmt.. Die pharmakokinetischen Parameter von Oclacitinib bei der Katze sind ähnlich wie die für den Hund beschriebenen, obwohl die Absorption und Eliminierung etwas schneller sind und die Variabilität zwischen den Individuen etwas größer. Große Dosen und/oder kürzere Dosierungsintervalle sollten bei den Katzen empfohlen werden, um ähnliche Blutkonzentrationen wie jene der Hunde zu erreichen.. 背景: 奥拉替尼已被证明是一种两面神激酶(JK)1抑制剂,在治疗犬过敏性皮炎上安全有效。由于缺乏药代动力学数据,给猫的使用受到了限制。 目的: 测定口服和静脉给药后奥拉替尼在猫体内的药代动力学参数。 动物: 六只成年短毛家猫。 方法和材料: 采用两期、两种治疗设计,猫分别接受马来酸奥克拉替尼静脉注射和口服。剂量分别为0.5 mg/kg和1 mg/kg。两次治疗之间有一周的间隔期。一种治疗每只猫只接受一次。采用高效液相色谱法测定静脉注射后0分钟、5分钟、15分钟、30分钟、1小时、4小时、6小时、10小时和24小时,以及口服给药后0分钟、15分钟、30分钟、1小时、2小时、4小时、6小时、10小时和24小时的奥拉替尼血浆浓度。 结果: 在口服给药后,奥拉替尼被迅速和几乎完全吸收,显示绝对生物利用度为87%,35分钟达到最大峰值。药物的消除也非常快速,显示半衰期2.3小时,间隙计算为4.45ml/min/kg(静脉注射治疗之后)。 结论和临床意义: 奥拉替尼在猫体内的药代动力学参数与犬相似,尽管吸收和消除更快,个体间的差异更大。建议在猫使用更大剂量和/或给药间隔更短,以达到与犬相似的血药浓度。.. O oclacitinib é um inibidor da Janus quinase (JK) 1 que demonstrou ser eficaz e seguro para o tratamento da dermatite alérgica em cães. Seu uso em gatos é limitado pela ausência de dados farmacocinéticos.. Determinar os parâmetros farmacocinéticos do oclacitinib em gatos após administração oral e intravenosa.. Seis gatos domésticos de pelo curto. MÉTODOS E MATERIAIS: Utilizou-se um delineamento experimental de dois períodos, dois tratamentos, no qual os gatos receberam maleato de oclacitinib IV e VO, na dose de 0,5 mg / kg e 1 mg / kg, respectivamente. Um intervalo de uma semana entre os dois tratamentos foi instituído para eliminação dos fármacos. Os gatos receberam cada tratamento apenas uma vez. A concentração plasmática de oclacitinib foi determinada por cromatografia líquida de alta eficiência aos 0 min, 5 min, 15 min, 30 min, 1 h, 4 h, 6 h, 10 h e 24 h após administração IV, aos 0 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, 10 h e 24 h depois de administração por VO.

Topics: Administration, Intravenous; Administration, Oral; Animals; Biological Availability; Cats; Dermatitis, Atopic; Dermatologic Agents; Male; Pyrimidines; Sulfonamides

Hyperkeratotic erythema multiforme (HKEM) is a clinically distinct dermatosis and poorly characterized syndrome, comprised of hyperkeratotic plaques with variable symmetry and apoptosis similar to "classic" erosive canine EM. Hyperkeratotic EM has a protracted clinical course and, although treatments with glucocorticoids, azathioprine and/or ciclosporin have been tried, rates of remission are low.. To describe successful treatment of HKEM in two dogs using oclacitinib.. A 7-year-old, spayed Havanese dog (Case 1) and a 1-year-old, intact cryptorchid Dachshund dog (Case 2).. Case characterization and clinical diagnoses were based on lesion character, surgical biopsy, cytological evaluation, culture, direct immunofluorescence (DIF) and expected responses to treatments.. Both cases exhibited multifocal, often symmetrical hyperkeratotic plaques with adherent scale. Histological findings revealed prominent epidermal hyperplasia, parakeratotic hyperkeratosis, lymphocytic dermatitis and transepidermal apoptosis with lymphocytic satellitosis. DIF revealed fine, patchy IgG, IgM and IgA basement membrane deposits (Case 2). Both dogs exhibited rapid improvement with oral oclacitinib (0.6-0.9 mg/kg twice daily) with a complete remission of clinical signs observed in 12 and seven weeks in cases 1 and 2, respectively.. Oclacitinib could be considered as a fast-acting and effective treatment option for HKEM in dogs.. L’érythème polymorphe hyperkératosique (HKEM) est une dermatose cliniquement distincte et un syndrome peu caractérisé, comprenant des plaques hyperkératosiques de symétrie variable et de l'apoptose semblable à l’EM canine érosive « classique ». L’EM hyperkératosique a une évolution clinique au long cours et bien que des traitements avec corticoïdes, azathioprine et/ou ciclosporine aient été essayés, les taux de rémission sont faibles.. Décrire un traitement efficace de l’HKEM chez deux chiens à l'aide d'oclacitinib.. Un chien bichon havanais de 7 ans (Cas 1) et un teckel cryptorchide entier de 1 an (Cas 2). MÉTHODES: La caractérisation du cas et le diagnostic clinique ont été basés sur les lésions, les biopsies, la cytologie, la culture, l'immunofluorescence directe (DIF) et les réponses attendues aux traitements. RÉSULTATS: Les deux cas ont montré des plaques hyperkératosiques, souvent symétriques, multifocales avec squames adhérentes. Les données histologiques ont montré une hyperplasie épidermique proéminente, de l'hyperkératose parakératosique, une dermatite lymphocytaire et de l'apoptose transépidermique avec satellitose lymphocytaire. Le DIF a révélé des dépôts en patch d'IgG, IgM et IgA sur la membrane basale (Cas 2). Les deux chiens ont montré une amélioration rapide avec de l'oclacitinib oral (0.6-0.9 mg/kg deux fois par jour) avec rémission complète des signes cliniques observés en 12 et sept semaines respectivement dans les cas 1 et 2.. L'oclacitinib pourrait être considéré comme une option thérapeutique rapide et efficace pour l’HKEM chez le chien.. INTRODUCCIÓN: el eritema multiforme hiperqueratótico (HKEM) es una dermatosis clínicamente distinta y un síndrome mal caracterizado, compuesto por placas hiperqueratóticas con simetría variable y apoptosis similar a la EM canina erosiva “clásica”. La EM hiperqueratótica tiene un curso clínico prolongado y, aunque se han intentado tratamientos con glucocorticoides, azatioprina y/o ciclosporina, las tasas de remisión son bajas. OBJETIVOS: describir el tratamiento exitoso de HKEM en dos perros tratados con oclacitinib. ANIMALES: un perro Havanés esterilizado de 7 años de edad (caso 1) y un perro Dachshund criptórquido intacto de 1 año de edad (caso 2). MÉTODOS: la caracterización de casos y los diagnósticos clínicos se basaron en el carácter de la lesión, la biopsia quirúrgica, la evaluación citológica, el cultivo, la inmunofluorescencia directa (DIF) y las respuestas esperadas a los tratamientos. RESULTADOS: ambos casos exhibieron placas hiperqueratóticas multifocales, a menudo simétricas, con escamas adherentes. Los hallazgos histológicos revelaron hiperplasia epidérmica prominente, hiperqueratosis paraqueratótica, dermatitis linfocítica y apoptosis transepidérmica con satelitósis linfocítica. DIF reveló depósitos de membrana basal IgG, IgM e IgA finas y discontinuas (Caso 2). Ambos perros mostraron una mejoría rápida con oclacitinib oral (0,6-0,9 mg/kg dos veces al día) con una remisión completa de los signos clínicos observados en 12 y siete semanas en los casos 1 y 2, respectivamente. CONCLUSIÓN E IMPORTANCIA CLÍNICA: Oclacitinib podría considerarse como una opción de tratamiento de acción rápida y eficaz para HKEM en perros.. Das hyperkeratotische Erythema multiforme (HKEM) ist eine klinisch deutlich abgegrenzte Dermatose, aber ein schlecht beschriebenes Syndrom, welches aus hyperkeratotischen Plaques mit unterschiedlicher Symmetrie und Apoptose, ähnlich dem „klassischen“ erosiven EM des Hundes, besteht. Das hyperkeratotische EM zeigt einen langwierigen klinischen Verlauf und, obwohl Behandlungen mit Glukokortikoiden, Azathioprin und/oder Ciclosporin versucht worden sind, sind die Remissionsraten niedrig.. Die Beschreibung einer erfolgreichen Behandlung von HKEM bei zwei Hunden mittels Oclacitinib.. Eine 7 Jahre alte kastrierte Havaneserhündin (Fall 1) und ein 1 Jahre alter intakter kryptorchider Dackelrüde (Fall 2).. Die Fallbeschreibung sowie die Beschreibung der klinischen Diagnosen basierte auf dem Aussehen der Läsionen, der chirurgischen Biopsie, der zytologischen Evaluierung, der Kultur, der direkten Immunfluoreszenz (DIF) und der erwarteten Behandlungserfolge.. Beide Fälle zeigten multifokale, oft symmetrische hyperkeratotische Plaques mit anhaftenden Schuppen. Die histologischen Befunde zeigten eine prominente epidermale Hyperplasie, eine parakeratotische Hyperkeratose, eine lymphozytäre Dermatitis und eine transepidermale Apoptose mit lymphozytärer Satellitenbildung. Die DIF zeigte feine, fleckige Ablagerungen von IgG, IgM und IgA in der Basalmembran (Fall 2). Beide Hunde zeigten eine schnelle Verbesserung mit Oclacitinib per os (0,6-0,9 mg/kg zweimal täglich), wobei eine völlige Remission der klinischen Zeichen innerhalb von 12 bzw sieben Wochen in den Fällen 1 bzw 2 gesehen wurden.. Oclacitinib könnte als schnell-wirkende und wirksame Behandlungsoption für HKEM bei Hunden in Frage kommen.. 背景: 過角化性多形紅斑(HKEM)は、臨床的に異なる皮膚疾患であり、対称性で可変的な過角化性性局面および「古典的な」犬のびらん性EMに類似したアポトーシスで構成される、特徴が不十分な症候群である。過角化性EMは長期にわたる臨床経過をたどり、グルココルチコイド、アザチオプリン、および/またはシクロスポリンによる治療が試みられているが、寛解率は低い。 目的: 本研究の目的は、オクラシチニブ使用による2頭の犬のHKEMの成功した治療について説明することであった。 供試動物: 7歳、避妊雌、ハバニーズ(症例1)と1歳、停留精巣の雄、ダックスフンド(症例2)。 方法: 症例の特徴付けおよび臨床診断は、病変の特徴、外科的生検、細胞学的評価、培養、直接免疫蛍光法(DIF)、および治療に対する期待される反応に基づいた。 結果: どちらの症例も、付着性の鱗屑を伴う多巣性で、しばしば対称性の過角化性局面を示した。組織学的所見は、顕著な表皮過形成、不全角化性角化症、リンパ球性皮膚炎、およびリンパ球性サテライトーシスを伴う経皮アポトーシスを明らかにした。 DIFにより、細かいパッチ状のIgG、IgM、IgAの基底膜の沈着が明らかになった(症例2)。どちらの症例も経口オクラシチニブ(0.6-0.9 mg / kg 1日2回)で急速な改善を示し、症例1および2ではそれぞれ12週間および7週間で臨床症状の完全寛解が観察された。 結論と臨床的重要性: オクラシチニブは、犬のHKEMに即効性があり効果的な治療オプションと考えることができる。.. 背景: 过度角化性多形红斑 (HKEM) 是一种临床上独特的皮肤病,这种综合征的特征较少,包括可能对称发生的过度角化性斑块,以及类似于“典型”糜烂性犬EM的细胞凋亡。过度角化性 EM 的临床病程持久,尽管已尝试使用糖皮质激素、硫唑嘌呤和/或环孢素治疗,但缓解率较低。 目的: 报告使用奥拉替尼成功治疗的两只HKEM患犬。 动物: 一只 7 岁、切除卵巢的哈瓦犬(病例 1)和一只 1 岁、未去势隐睾腊肠犬(病例 2)。 方法: 病例特征和临床诊断基于病变特征、外科活检、细胞学评价、培养、直接免疫荧光 (DIF) 和预期的治疗反应。 结果: 两个病例均表现出多灶性、通常对称的过度角化性斑块,伴粘附性鳞屑。组织学的调查结果揭示了突出的表皮增生,角化不全性过度角化病,淋巴细胞性皮炎,以及伴随淋巴细胞性卫星现象的跨表皮细胞凋亡。DIF 显示点、片状 IgG、IgM 和 IgA 基底膜沉积(病例 2)。口服给予奥拉替尼(0.6-0.9 mg/kg,每日两次)后,两只犬均表现出快速改善,在病例 1 和 2 中,分别在 12 周和 7 周内观察到临床体征完全缓解。 结论和临床意义: 奥拉替尼可被认为是犬 HKEM 的一种速效和有效的治疗选择。.. O eritema multiforme hiperqueratótico (HKEM) é uma dermatose clinicamente distinta e uma síndrome pouco caracterizada, composta por placas hiperqueratóticas com simetria e apoptose variáveis ​​semelhantes ao EM canino erosivo “clássico”. O EM hiperqueratótico apresenta um quadro clínico prolongado e, apesar de tratamentos com glicocorticóides, azatioprina e/ou ciclosporina tenham sido tentados, as taxas de remissão são baixas.. Descrever o tratamento bem-sucedido do HKEM em dois cães usando oclacitinib.. Um cão Havanese de 7 anos, castrado (Caso 1), e um cachorro Dachshund com criptorquidia intacto de 1 ano (Caso 2). MÉTODOS: A descrição do caso e o diagnóstico clínico foram baseados nas características da lesão, biópsia cirúrgica, avaliação citológica, cultura, imunofluorescência direta (IFD) e respostas esperadas aos tratamentos.. Ambos os casos apresentaram placas hiperqueratóticas multifocais, muitas vezes simétricas, com escama aderida. Os achados histológicos revelaram hiperplasia epidérmica proeminente, hiperqueratose paraqueratótica, dermatite linfocítica e apoptose transepidérmica com satelitose linfocítica. A IFD revelou depósitos finos e irregulares de IgG, IgM e IgA na membrana basal (Caso 2). Ambos os cães apresentaram melhora rápida com oclacitinib oral (0,6-0,9 mg / kg duas vezes ao dia) com remissão completa dos sinais clínicos observados em 12 e sete semanas nos casos 1 e 2, respectivamente. CONCLUSÃO E IMPORTÂNCIA CLÍNICA: Oclacitinib pode ser considerado uma opção de tratamento de ação rápida e eficaz para HKEM em cães.

Topics: Animals; Dermatitis, Atopic; Dog Diseases; Dogs; Erythema Multiforme; Female; Pyrimidines; Skin Diseases; Sulfonamides; Treatment Outcome

Ischaemic dermatopathy represents a heterogenous and poorly-characterized canine syndrome that is often refractory to conventional immunosuppression. Janus-kinase inhibitors (JAKinibs) are used for the treatment of various human autoimmune diseases, including dermatomyositis. Oclacitinib is a generally well-tolerated, veterinary-approved, nonselective JAKinib that has therapeutic potential as an immunosuppressant.. To describe four cases of treatment refractory juvenile-onset ischaemic dermatopathy that rapidly and durably responded to oclacitinib administration.. Four mixed-breed dogs, three 9-month-old male littermates and one 6-month-old female, were presented for generalized patchy alopecia, scarring and ulcerative dermatitis. Microscopic skin lesions were consistent with a severe ischaemic dermatopathy.. A complete remission of skin lesions could not be achieved in any dog with glucocorticoids alone, nor when these were combined with adjuvant immunosuppressants. Oclacitinib treatment was then initiated at the dosage of 0.4-0.7 mg/kg twice daily, along with a tapering regimen of oral prednisolone.. A full clinical remission was achieved within four weeks of starting this combination therapy, with prednisolone being stopped within eight weeks thereof. Remission was maintained in two dogs with lower doses or dosing frequencies of oclacitinib, whereas the two others required persistent twice daily administration of this JAKinib.. Oclacitinib was a useful immunosuppressive adjuvant to oral glucocorticoids for the treatment of refractory or severe cases of ischaemic dermatopathy in these four dogs. Such observation warrants further studies of the safety, efficacy and mechanism of action of oclacitinib as an immunosuppressant.. La dermatopathie ischémique représente un syndrome canin hétérogène faiblement caractérisé souvent réfractaire aux immunosuppresseurs classiques. Les inhibiteurs de Janus-kinase (JAKinibs) sont utilisés pour le traitement de maladies auto-immunes de l'homme y compris la dermatomyosite. L'oclacitinib est généralement bien supporté, disponible en médecine vétérinaire, inhibiteur de JAK non sélectif qui peut avoir des propriétés immunosuppressives potentielles. HYPOTHÈSES/OBJECTIFS: Décrire quatre cas réfractaires aux traitements de dermatopathie ischémique juvénile qui répondent rapidement et durablement à l'oclacitinib.. Quatre chiens croisés, trois mâles de 9 mois et une femelle de 6 mois, ont été présentés pour dermatite généralisée ulcérative et cicatricielle et alopécique en patch. Les lésions cutanées microscopiques étaient compatibles avec une dermatite ischémique sévère. MATÉRIEL ET MÉTHODE: Une rémission complète des lésions cutanées n'a pas pu être obtenue avec des corticoïdes seuls ni avec en association à un immunosuppresseur adjuvant. Le traitement à l'oclacitinib a été initié à la dose de 0,4-0,7 mg/kg deux fois par jour associé à un traitement dégressif de prednisolone oral. RÉSULTATS: Une rémission clinique complète a été atteinte en quatre semaines avec la prednisolone stoppée au bout de huit semaines. La rémission a été maintenue pour deux chiens avec de faibles doses d'oclacitinib tandis que les deux autres ont nécessité une administration de l'inhibiteur de JAK deux fois par jour.. L'oclacitinib semble être un immunosuppresseur adjuvant utile aux corticoïdes oraux pour le traitement des cas sévères de dermatopathie ischémique pour ces quatre chiens. D'autres études sont nécessaires pour compléter ces observations pour l'innocuité, l'efficacité et le mécanisme d'action de l'oclacitinib en tant qu'immunosuppresseur.. INTRODUCCIÓN: la dermatopatía isquémica representa un síndrome canino heterogéneo y mal caracterizado que a menudo es refractario a la inmunosupresión convencional. Los inhibidores de Janus-kinase (JAKinibs) se utilizan para el tratamiento de diversas enfermedades autoinmunes humanas, incluida la dermatomiositis. Oclacitinib es un JAKinib no selectivo, bien tolerado, aprobado para uso veterinario, que tiene un potencial terapéutico como inmunosupresor. HIPÓTESIS/OBJETIVOS: Describir cuatro casos de presumible dermatopatía isquémica juvenil refractarios a tratamiento que respondieron de forma rápida y duradera a la administración de oclacitinib. ANIMALES: se presentaron cuatro perros de raza mestiza, tres de ellos de la misma camada de 9 meses de edad y una hembra de 6 meses de edad con una alopecia multifocal generalizada, cicatrización y dermatitis ulcerativa. Las lesiones microscópicas de la piel fueron compatibles con una dermatopatía isquémica intensa. MÉTODOS Y MATERIALES: no se pudo lograr una remisión completa de las lesiones cutáneas en ningún perro solo con glucocorticoides, ni cuando se combinaron con inmunosupresores adyuvantes. Se inicio entonces el tratamiento con oclacitinib a una dosis de 0,4-0,7 mg/kg dos veces al día, junto con un régimen de reducción gradual de prednisolona oral. RESULTADOS: se logró una remisión clínica completa dentro de las cuatro semanas posteriores al inicio de esta terapia de combinación, deteniéndose la prednisolona dentro de las ocho semanas posteriores. La remisión se mantuvo en dos perros con dosis más bajas o menores frecuencias de dosificación de oclacitinib, mientras que los otros dos requirieron la administración persistente dos veces al día de este JAKinib. CONCLUSIONES E IMPORTANCIA CLÍNICA: el oclacitinib parece ser un adyuvante inmunosupresor útil con los glucocorticoides orales para el tratamiento de casos refractarios o graves de dermatopatía isquémica en estos cuatro perros. Esta observación indica la necesidad de estudios adicionales sobre seguridad, eficacia y mecanismo de acción del oclacitinib como inmunosupresor.. Eine ischämische Dermatopathie repräsentiert ein heterogenes und schlecht charakterisiertes Syndrom beim Hund, welches oft refraktär auf konventionelle Immunsuppression reagiert. Für die Behandlung verschiedener humaner Autoimmunerkrankungen wie auch für die Dermatomyositis werden Janus-Kinase Inhibitoren (JAKinibs) eingesetzt. Oclacitinib ist ein generell gut verträglicher, veterinärmedizinisch zugelassener, nichtselektiver JAKinib, welcher therapeutisches Potential als ein Immunsuppressivum aufweist.. Die Beschreibung von vier Fällen einer refraktären vermeintlichen, beim Jugendlichen auftretenden, ischämischen Dermatopathie, die rasch und dauerhaft auf eine Oclacitinib Verabreichung reagierte.. Vier Mischlingshunde, drei 9 Monate alte männliche Geschwister und eine 6 Monate alte Hündin wurden mit einer generalisierten fleckigen Alopezie, Narbenbildung und einer ulzerativen Dermatitis vorgestellt. Die mikroskopischen Hautveränderungen waren vereinbar mit einer hochgradigen ischämischen Dermatopathie.. Eine völlige Remission der Hautveränderungen konnte bei keinem der Hunde ausschließlich mit Glukokortikoiden erzielt werden, dies gelang nur, wenn diese mit zusätzlichen Immunsuppressiva kombiniert wurden. Daraufhin wurde Oclacitinib bei einer Dosierung von 0,4-0,7 mg/kg zweimal täglich eingesetzt, gleichzeitig wurde Prednisolon per os ausgeschlichen.. Eine völlige klinische Remission wurde innerhalb von vier Wochen nach Beginn der Kombinationstherapie erzielt, wobei Prednisolon innerhalb von acht Wochen gestoppt wurde. Eine Remission konnte bei zwei Hunden mit einer niedrigeren Dosierung oder einer Verringerung der Verabreichungsfrequenz von Oclacitinib erzielt werden, während die beiden anderen Hunde eine andauernde zweimal tägliche Verabreichung dieses JAKinib benötigten.. Oclacitinib schien ein nützliches Immunsuppressivum als Adjuvant zu oralen Glukokortikoiden für die Behandlung von hartnäckigen oder schweren Fällen von ischämischer Dermatopathie zu sein. Eine derartige Beobachtung rechtfertigt weitere Studien über die Sicherheit, Wirksamkeit und den Wirkungsmechanismus von Oclacitinib als Immunsuppressivum.. 背景: 虚血性皮膚症は、従来の免疫抑制にはしばしば抵抗性で、異質性で特徴が乏しい犬の症候群である。ヤヌスキナーゼ阻害剤(JAKinib)は、皮膚筋炎を含む様々な人の自己免疫疾患の治療に使用されている。オクラシチニブは、免疫抑制剤としての治療可能性を有した、一般的に忍容性が高く、獣医学的に承認された、非選択的なJAKinibである. 仮説/目的: 本研究の目的は、オクラシチニブ投与に迅速かつ持続的に反応した、治療難治性と推定される若年発症虚血性皮膚症の4症例を記述することである. 被験動物: 汎発性に斑状脱毛、瘢痕および潰瘍性皮膚炎を認めた4頭のMIX犬(9ヶ月齢の同腹仔の雄3頭および6ヶ月齢の雌1頭)。顕微鏡的皮膚病変は重度の虚血性皮膚症と一致していた. 材料と方法: どの犬でも、グルココルチコイド単独あるいはアジュバント免疫抑制薬との組み合わせでは、皮膚病変の完全寛解は達成できなかった。次いで、オクラシチニブ治療を経口プレドニゾロンの漸減投与計画と共に、1日2回、0.4〜0.7 mg/kgの用量で開始した. 結果: この併用療法を開始してから4週間以内に完全な臨床的寛解を達成し、プレドニゾロンは8週間以内に中止した。オクラシチニブの用量または投与頻度の減少させた2頭の犬で寛解を維持したが、他の2頭はこのJAKinibの1日2回の持続投与を必要とした. 結論と臨床的重要性: オクラシチニブは、本研究の犬4頭における難治性または重度の虚血性皮膚症治療に対し、経口グルココルチコイドの有用な免疫抑制アジュバントであるように思われた。そのような結果は、免疫抑制剤としてのオラシチニブの安全性、有効性および作用機序のさらなる研究を保証するものである.. 背景: 缺血性皮肤病是一种异质且缺乏特征的犬综合征,通常用传统的免疫抑制难以治愈。Janus-激酶抑制剂(JAKinibs)用于治疗多种人类自身免疫疾病,包括皮肌炎。奥克拉克替尼是一种耐受性良好、兽医认可的非选择性JAKinib,可以作为免疫抑制剂治疗. 假设/目的: 描述四个推定性幼年发病的缺血性皮肤病的顽固病例,奥克拉克替尼治疗效果快速且持久. 动物: 四只呈现全身性脱毛斑、瘢痕和溃疡性皮炎的混血犬,其中三只为9月龄同窝公犬,以及一只6月龄母犬。镜检发现其皮肤病变为严重的缺血性皮肤病. 方法和材料: 任何犬单独使用糖皮质激素,或与免疫抑制剂联合使用,都不能完全缓解皮肤病变。随后,开始给予奥克拉克替尼,剂量0.4-0.7mg/kg,每日两次,伴随逐渐减量的泼尼松龙口服. 结果: 在开始这种联合治疗的四周内,临床症状完全缓解,其中泼尼松龙在八周内停用。两只犬用低剂量或低频率的奥克拉克替尼维持,而另两只犬则需要持续每日两次给予这种JAKinib. 结论和临床价值: 奥克拉克替尼对口服糖皮质激素来说,显然是一种有效的辅助免疫抑制剂,用于治疗这四只犬的顽固或严重缺血性皮肤病。根据这一观察结果,奥克拉克替尼作为免疫抑制剂的安全性、有效性和作用机制,需进一步研究.. A dermatopatia isquêmica representa uma síndrome canina heterógena e pouco caracterizada que é refratária à imunossupressão convencional. Os inibidores da Janus-quinase (JAKinibs) são utilizados para o tratamento de diversas doenças autoimunes em humanos, incluindo a dermatomiosite. O oclacitinib é um JAKinib não seletivo geralmente bem tolerado, de uso veterinário que possui um potencial terapêutico como imunossupressor. HIPÓTESE/OBJETIVOS: Descrever quatro casos presuntivos de dermatopatia isquêmica juvenil refratária ao tratamento convencional que responderam rapidamente e duradouramente à administração de oclacitinib.. Quatro cães mestiços, três machos de nove meses de idade, irmãos da mesma ninhada, e uma fêmea de seis meses de idade, foram apresentados com alopecia multifocal, fibrose e dermatite ulcerativa. As lesões cutâneas microscópicas foram compatíveis com dermatopatia isquêmica grave. MÉTODOS E MATERIAIS: Não foi possível se obter remissão completa das lesões cutâneas em nenhum dos cães somente com corticoterapia, nem mesmo em associação com imunossupressores adjuvantes. O tratamento com oclacitinib foi iniciado em uma dose de 0,4-0,7 mg/kg duas vezes ao dia, juntamente com o protocolo de redução gradativa da prednisolona.. Resolução clínica completa foi alcançada dentro de quatro semanas após o início da terapia combinada, com a interrupção da prednisolona em oito semanas. A remissão foi mantida em dois cães com baixas doses ou menor frequência de administração de oclacitinib, enquanto os outros dois cães necessitaram de administração contínua de deste JAKinib duas vezes ao dia. CONCLUSÕES: O oclacitinib parece ser um imunossupressor útil como adjuvante aos glicocorticoides orais no tratamento de casos de casos graves de dermatopatia isquêmica refratária nesses quatro cães. Tal observação justifica novos estudos sobre segurança, eficácia e mecanismos de ação do oclacitinib como imunossupressor.

Topics: Animals; Autoimmune Diseases; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Female; Glucocorticoids; Male; Pyrimidines; Skin Diseases; Sulfonamides; Treatment Outcome

To evaluate the adjunctive effect of supplementation with Enterococcus faecium SF68 (FortiFlora; Purina Pro Plan Veterinary Diets) on oclacitinib (Apoquel, Zoetis) dose reduction, while maintaining or reducing the Pruritus Visual Analog Score and Canine Atopic Dermatitis Extent and Severity Index values in client-owned adult dogs with environmental atopic dermatitis.. Supplementation with SF68 was associated with no difference in oclacitinib dose reduction versus placebo in 21 client-owned dogs with atopic dermatitis. Clinical disease scores were not different between groups at study completion.. Further larger-scale studies are warranted to investigate optimal strain(s), dosing and duration of probiotic supplementation as an adjunctive strategy in management of canine atopic dermatitis.

Topics: Animals; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Enterococcus faecium; Pilot Projects; Pyrimidines; Sulfonamides

Topics: Animals; Antibodies, Monoclonal; Cyclosporine; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Glucocorticoids; Pyrimidines; Sulfonamides

Oclacitinib is a selective Janus kinase inhibitor for the treatment of canine allergic pruritus and atopic dermatitis in dogs. Glucocorticoids and ciclosporin increase urinary tract infection (UTI) frequency in dogs with inflammatory skin disease.. Prospective study to evaluate the frequency of UTI and subclinical bacteriuria in dogs with allergic dermatitis receiving oclacitinib.. Client-owned dogs ≥2 years of age with a history of allergic dermatitis without apparent history of urinary tract disease or predisposition to UTI were included. Prior to enrolment, urinalysis and quantitative urine culture were performed after a washout period of at least 14 days from systemic antimicrobial drugs and 28 days for ciclosporin and systemic glucocorticoids. Dogs received oclacitinib at labelled dosing for an intended period of 180-230 days with a follow-up urinalysis and urine culture performed regardless of urinary tract signs. Systemic antimicrobial and immune-modulating drugs were not administered during the study.. None of the 55 dogs in this study developed UTI while receiving oclacitinib based on follow-up urinalysis and urine culture performed during a range of 58-280 days (mean 195 days). Two dogs developed self-limiting abnormal urinary tract signs without urine culture or urinalysis findings consistent with UTI.. These findings indicate that bacteriuria is not an expected adverse effect in dogs treated with oclacitinib without a prior history of UTI or predisposing condition during this treatment period. Therefore, routine urine culture is not indicated for such dogs in the absence of abnormal urinalysis or clinical signs of urinary tract disease.

Topics: Animals; Asymptomatic Infections; Bacteriuria; Dermatitis, Atopic; Dermatologic Agents; Dog Diseases; Dogs; Female; Male; Prospective Studies; Pyrimidines; Sulfonamides; Urinary Tract Infections

Oclacitinib is a Janus kinase inhibitor that decreases pruritus and lesions in allergic dogs. In cats, it is able to inhibit interleukin-31-induced pruritus; no information is available on its clinical effectiveness.. To evaluate the efficacy, ease of administration and tolerability of oclacitinib in feline nonflea-, nonfood-induced hypersensitivity dermatitis.. Cats >12 months of age and >3 kg body weight with a diagnosis of nonflea-, nonfood-induced hypersensitivity dermatitis were treated with oclacitinib, 0.4-0.6 mg/kg orally (p.o.) twice daily for 2 weeks, then once daily for an additional 14 days. Clinical lesions were evaluated with the Scoring Feline Allergic Dermatitis (SCORFAD) system and pruritus was evaluated with a 10-cm-long visual analog scale (VAS) before and at the end of the study. Owners assessed global efficacy, ease of administration and tolerability with a four-point scale.. Twelve cats were treated with a mean initial oclacitinib dose of 0.47 mg/kg p.o. twice daily. There was good improvement in SCORFAD and VAS pruritus scores in five of 12 cases, while the other cats were unchanged, deteriorated or dropped out due to treatment failure. Owners scored global efficacy as good/excellent in four of 12 cases and ease of administration and tolerability as good/excellent in 10 of 12.. Oclacitinib at 0.4-0.6 mg/kg p.o. may be an effective and safe drug for some cats with nonflea-, nonfood-induced hypersensitivity dermatitis. Further studies are needed to identify the most effective dose range for this species.

Topics: Animals; Cat Diseases; Cats; Dermatitis, Atopic; Dermatologic Agents; Female; Male; Pilot Projects; Prospective Studies; Pyrimidines; Sulfonamides; Treatment Outcome

Janus kinase (JAK) inhibitors have recently been developed for allergic diseases. We focused on the 2 different JAK inhibitors, tofacitinib (selective for JAK3) and oclacitinib (selective for JAK1 and 2), to clarify the mechanism of anti-inflammatory and anti-itching potency of these drugs. In the process of detecting anti-itching potency, we observed that tofacitinib treated mice showed aggression behaviour. The objective of the study reported here was to investigate the aggressive behaviour induced by tofacitinib by using a mouse model of allergic dermatitis and the resident-intruder test. For the allergic dermatitis model, female BALB/c mice were sensitised and challenged topically with toluene-2,4-diisocyanate (TDI). Vehicle, tofacitinib or oclacitinib, was administered orally 30 min before TDI challenge. Scratching, aggression and standing behaviours were monitored in the 60 min period immediately following challenge of TDI. Another group of male BALB/c mice treated with vehicle, tofacitinib or oclacitinib was evaluated in the resident-intruder test and brains were obtained to determine blood brain barrier penetration. In the allergic dermatitis model, a significant increase in aggression and standing behaviour was only obvious in the tofacitinib treatment group. There was no effect in non-sensitised mice, but similar aggression was also induced by tofacitinib in male resident-intruder test. Penetration of blood-brain barrier was observed both in tofacitinib and oclacitinib treated mice. These results suggest that aggression was induced by tofacitinib under some kind of stressful environment. This study indicates a possible role of the JAK-STAT pathway in modulation of aggression behaviour.

Topics: Administration, Oral; Aggression; Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Behavior, Animal; Brain; Dermatitis, Atopic; Disease Models, Animal; Female; Janus Kinases; Male; Mice, Inbred BALB C; Piperidines; Protein Kinase Inhibitors; Pruritus; Pyrimidines; Pyrroles; Stress, Psychological; Sulfonamides; Toluene 2,4-Diisocyanate