The anti‐inflammatory effect of topical tofacitinib on immediate and late‐phase cutaneous allergic reactions in dogs: a placebo‐controlled pilot study

Background Topical Janus kinase (JAK) inhibition is a promising therapeutic target for several inflammatory skin diseases of humans. Objectives To evaluate the anti‐inflammatory effect of tofacitinib, a JAK 1/3 inhibitor, on immediate and late‐phase skin reactions in dogs. Animals Five healthy laboratory beagle dogs. Methods Topical tofacitinib (total daily dosage: 0.5 mg/cm2) or its gel vehicle were applied on either the left or right lateral thorax of each dog for eight days. Three days before application and after eight days of topical treatment, intradermal injections of histamine and anticanine‐IgE antibodies were performed on both sides; they were evaluated by an investigator blinded to the interventions. Results The tofacitinib gel was well‐tolerated; one dog developed mild erythema at Day 5 that resolved by the next application. Treatment with tofacitinib reduced histamine and anticanine‐IgE global wheal scores (one‐way ANOVA, P ≤ 0.005 for both) compared to baseline; there was no significant difference for the vehicle placebo (histamine; P = 0.163; IgE, P = 0.223). Late‐phase reactions (LPRs) were markedly, but not significantly reduced after tofacitinib treatment (P = 0.071). A blinded histological evaluation of 6 h‐anti‐IgE‐associated LPRs revealed a significant reduction in the total leucocyte superficial dermal cellularity (P = 0.022), as well as eosinophil (P = 0.022) and mast cell (P = 0.022) counts at tofacitinib‐treated sides compared with pretreatment values. Post‐treatment complete blood counts and serum chemistry profiles did not show relevant tofacitinib‐induced changes. Conclusions Our observations suggest that topical tofacitinib exerts an inhibitory effect on activated canine skin‐emigrating immune cells; this drug should be investigated further as a topical immunosuppressive drug in dogs. Résumé Contexte L'inhibition topique des JAK (Janus Kinase) est une cible thérapeutique prometteuse pour plusieurs maladies inflammatoires cutanées de l'homme. Objectifs Evaluer l'effet anti‐inflammatoire du tofacitinib, un inhibiteur de JAK 1/3, sur les réactions cutanées immédiates et retardées chez le chien. Sujets Cinq chiens beagles de laboratoire en bonne santé. Méthodes Le tofacitinib topique (dosage total quotidien : 0.5mg/ cm2) ou son véhicule en gel ont été appliqués pour chaque chien soit sur le thorax latéral gauche soit sur le droit pendant 8 jours. Trois jours avant et 8 jours après le traitement topique, des injections intradermique