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The anti‐inflammatory effect of topical tofacitinib on immediate and late‐phase cutaneous allergic reactions in dogs: a placebo‐controlled pilot study
Author(s) -
Blubaugh Amanda,
Rissi Daniel,
Elder Deborah,
Denley Tara,
EguiluzHernandez Sitka,
Banovic Frane
Publication year - 2018
Publication title -
veterinary dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.744
H-Index - 60
eISSN - 1365-3164
pISSN - 0959-4493
DOI - 10.1111/vde.12532
Subject(s) - tofacitinib , medicine , erythema , histamine , placebo , janus kinase inhibitor , immunoglobulin e , allergy , pharmacology , gastroenterology , dermatology , immunology , antibody , pathology , rheumatoid arthritis , alternative medicine
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/cm 2 ) 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 ( LPR s) were markedly, but not significantly reduced after tofacitinib treatment ( P = 0.071). A blinded histological evaluation of 6 h‐anti‐IgE‐associated LPR s 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.