oclacitinib and Pruritus

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

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 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

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

Oclacitinib (Apoquel(®) ) inhibits the function of a variety of pro-inflammatory, pro-allergic and pruritogenic cytokines that are dependent on Janus kinase enzyme activity. Oclacitinib selectively inhibits Janus kinase 1.. We aimed to evaluate the safety and efficacy of oclacitinib for the control of pruritus associated with allergic dermatitis in a randomized, double-blinded, placebo-controlled trial.. Client-owned dogs (n = 436) with moderate to severe owner-assessed pruritus and a presumptive diagnosis of allergic dermatitis were enrolled. Dogs were randomized to either oclacitinib at 0.4-0.6 mg/kg orally twice daily or an excipient-matched placebo. An enhanced 10 cm visual analog scale (VAS) was used by the owners to assess the severity of pruritus from day 0 to 7 and by veterinarians to assess the severity of dermatitis on days 0 and 7. Dogs could remain on the study for 28 days.. Pretreatment owner and veterinary VAS scores were similar for the two treatment groups. Oclacitinib produced a rapid onset of efficacy within 24 h. Mean oclacitinib Owner Pruritus VAS scores were significantly better than placebo scores (P < 0.0001) on each assessment day. Pruritus scores decreased from 7.58 to 2.59 cm following oclacitinib treatment. The day 7 mean oclacitinib Veterinarian Dermatitis VAS scores were also significantly better (P < 0.0001) than placebo scores. Diarrhoea and vomiting were reported with similar frequency in both groups.. In this study, oclacitinib provided rapid, effective and safe control of pruritus associated with allergic dermatitis, with owners and veterinarians noting substantial improvements in pruritus and dermatitis VAS scores.

Topics: Animals; Dermatitis; Dermatologic Agents; Dog Diseases; Dogs; Double-Blind Method; Female; Hypersensitivity; Male; Pruritus; Pyrimidines; Sulfonamides

Topics: Animals; Cat Diseases; Cats; Dog Diseases; Dogs; Glucocorticoids; Pruritus; Pyrimidines; Sulfonamides

The janus kinase-inhibitor oclacitinib is licensed for the control of pruritus associated with allergic skin diseases in dogs. Strikingly, it has been clinically reported that abrupt withdrawal of oclacitinib leads to a rebound pruritus in dogs. Therefore, the primary objective of this study was to mimic the rebound phenomenon of oclacitinib using a chronic pruritic mouse model of allergic contact dermatitis. Chronic allergic contact dermatitis was induced by repetitive toluene-2,4-diisocyanate (TDI) challenge in BALB/c mice. Oclacitinib was orally administered twice daily at 45mg/kg for 7 days, with concurrent TDI challenge, and then treatment of oclacitinib was abruptly discontinued. Scratching bouts following TDI challenge were evaluated to day 15. Additionally, dorsal root ganglia (DRG) and affected skin were isolated from mice receiving oclacitinib and from mice 24h after oclacitinib withdrawal and were used to determine pruritogen induced Ca

Topics: Animals; Behavior, Animal; Calcium; CD11c Antigen; Cytokines; Dendritic Cells; Female; Ganglia, Spinal; Immunomodulation; Intracellular Space; Janus Kinase 1; Mice; Mice, Inbred BALB C; Protein Kinase Inhibitors; Pruritus; Pyrimidines; Sensory Receptor Cells; Skin; Sulfonamides; Tumor Necrosis Factor-alpha

Pruritus is a characteristic clinical sign of allergic skin conditions including atopic dermatitis (AD) in the dog. IL-31 is a cytokine found in the serum of some dogs with AD and can induce pruritic behaviours in laboratory beagle dogs.. The objectives were to characterize an IL-31-induced pruritus model by evaluating the efficacy of prednisolone, dexamethasone and oclacitinib, and to compare the speed of anti-pruritic effects of oclacitinib against those of prednisolone and dexamethasone.. Purpose-bred beagle dogs were used in all studies.. Randomized, blinded, placebo-controlled studies were designed to evaluate and compare the anti-pruritic properties of prednisolone, dexamethasone and oclacitinib following a single intravenous injection of recombinant canine IL-31. Video surveillance was used to monitor and score pruritic behaviours in study animals.. Prednisolone [0.5 mg/kg, per os (p.o.)] reduced IL-31-induced pruritus when given 10 h prior to observation. When the time interval between drug treatment and observation was shortened to 1 h, dexamethasone (0.2 mg/kg, intramuscular) but not prednisolone (0.25 or 0.5 mg/kg, p.o.) reduced IL-31-induced pruritus. Oclacitinib (0.4 mg/kg, p.o.) reduced pruritus when given 1, 6, 11 and 16 h prior to the observation period, and the anti-pruritic activity of oclacitinib was greater when compared to prednisolone and dexamethasone at all time points assessed.. The efficacy of prednisolone, dexamethasone and oclacitinib in the IL-31-induced pruritus model gives confidence that this may be a relevant model for acute pruritus associated with allergic dermatitis including AD and can be used to evaluate novel compounds or formulations.

Topics: Animals; Antipruritics; Dexamethasone; Dog Diseases; Dogs; Glucocorticoids; Interleukins; Prednisolone; Pruritus; Pyrimidines; Sulfonamides

The prevalence of allergic skin disorders has increased rapidly, and development of therapeutic agents to alleviate the symptoms are still needed. In this study, we orally or topically administered the Janus kinase (JAK) inhibitors, tofacitinib and oclacitinib, in a mouse model of dermatitis, and compared the efficacy to reduce the itch and inflammatory response. In vitro effects of JAK inhibitors on bone marrow-derived dendritic cells (BMDCs) were analyzed. For the allergic dermatitis model, female BALB/c mice were sensitized and challenged with toluene-2,4-diisocyanate (TDI). Each JAK inhibitor was orally or topically applied 30 minutes before and 4 hours after TDI challenge. After scratching bouts and ear thickness were measured, cytokines were determined in challenged skin and the cells of the draining lymph node were analyzed by means of flow cytometry. In vitro, both JAK inhibitors significantly inhibited cytokine production, migration, and maturation of BMDCs. Mice treated orally with JAK inhibitors showed a significant decrease in scratching behavior; however, ear thickness was not significantly reduced. In contrast, both scratching behavior and ear thickness in the topical treatment group were significantly reduced compared with the vehicle treatment group. However, cytokine production was differentially regulated by the JAK inhibitors, with some cytokines being significantly decreased and some being significantly increased. In conclusion, oral treatment with JAK inhibitors reduced itch behavior dramatically but had only little effect on the inflammatory response, whereas topical treatment improved both itch and inflammatory response. Although the JAK-inhibitory profile differs between both JAK inhibitors in vitro as well as in vivo, the effects have been comparable.

Topics: Administration, Oral; Administration, Topical; Animals; Anti-Inflammatory Agents; Antipruritics; Cytokines; Dermatitis, Allergic Contact; Disease Models, Animal; Female; Inflammation; Janus Kinases; Lymph Nodes; Mice; Mice, Inbred BALB C; Piperidines; Pruritus; Pyrimidines; Pyrroles; Skin; Sulfonamides

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

Preclinical Research The mechanisms mediating canine pruritus are poorly understood with few models due to limited methods for inducing pruritus in dogs. Chloroquine (CQ) is a widely used antimalarial drug that causes pruritus in humans and mice. We have developed a canine model of pruritus where CQ reliably induced pruritus in all dogs tested following intravenous administration. This model is presently being used to test antipruritic activity of drug candidate molecules. This publication has been validated in a blinded cross-over study in eight beagle dogs using the reference standards, oclacitinib and prednisolone, and has been used to test a new compound, norketotifen. All compounds reduced CQ-induced pruritus in the dog. The sensitivity of the model was demonstrated using norketotifen, which at three dose levels, dose-dependently, inhibited scratching events compared with placebo.

Topics: Animals; Antimalarials; Antipruritics; Chloroquine; Cross-Over Studies; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Female; Ketotifen; Male; Prednisolone; Pruritus; Pyrimidines; Sulfonamides