Anti-inflammatories for dogs: Tofacitinib in allergic reactions
Introduction
Various pathological reactions should be taken into account and an individualised approach applied in attempts to improve and control the signs of allergic skin disorders in dogs.
Currently, only a few treatment options are available and traditional topical corticosteroids still form the main basis of treatment. As for the choice of therapeutic agents for allergic skin disorders, here we focus on the use of Janus kinase (JAK) inhibitors which were developed for rheumatoid arthritis and pruritic inflammatory skin diseases.
Inhibitors
Mammals have four families of JAK enzymes (JAK1, JAK2, JAK3 and tyrosine kinase 2) and seven signal transducers and activators of transcription, which are used by over 50 cytokines and growth factors to mediate intracellular signalling. The proinflammatory cytokines that use the JAK pathway (interferon gamma and interleukin) are involved in diseases that provoke an inflammatory response. The cytokines produced by Th2 cells (IL-31 and TSLP) have a critical role in triggering pruritus.
Topically administered Janus kinase inhibitors, such as Tofacitinib, produce strong antipruritic and anti-inflammatory responses in dogs with allergic dermatitis. Preliminary safety and efficacy studies of tofacitinib use are very promising, and all the evidence suggests that it will soon be approved for use in human and veterinary medicine.
Tofacitinib has broad immunosuppressive activity. It preferably inhibits signalling by heterodimers that contain JAK3 and/or JAK1, with functional selectivity over the receptors that signal through JAK2 pairs.
A placebo-controlled pilot study was conducted to assess the anti-inflammatory effect of topical tofacitinib on immediate- and late-phase allergic skin reactions in dogs. Specifically, the study examined five healthy laboratory Beagles.
For 8 days, each dog was administered topical tofacitinib (daily dose: 0.5 mg/cm2) or the placebo gel on the right or left side of the chest. Histamine and anti-canine IgE antibodies were administered intradermally on both sides of the chest 3 days before and 8 days after the topical treatment.
The drug administered as a gel was well tolerated, with only one dog developing mild erythema on day 5 that resolved with the next application. Tofacitinib treatment reduced overall histamine and anti-canine IgE scores (one-way ANOVA, P = 0.005 for both) compared to baseline; there were no significant differences for the placebo gel (histamine, P = 0.163; IgE, P = 0.223).
There were fewer late-phase reactions (LPR) after tofacitinib treatment, but it was not a statistically significant reduction (P = 0.071). The results also showed a significant reduction from baseline values in total leukocyte superficial dermal cellularity (P = 0.022) and in eosinophil (P = 0.022) and mast cell counts (P = 0.022) on the sides where tofacitinib was applied.
Post-treatment haemograms and blood chemistry profiles did not reveal any relevant changes induced by tofacitinib.
We can conclude that tofacitinib exerts an inhibitory effect on activated immune cells in the skin of dogs and has few side effects.
