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Calcineurin Inhibitors (examples: ciclosporin, tacrolimus)
Ciclosporin (Atopicaâ – Novartis), is a calcineurin inhibitor that suppresses the production of inflammatory cytokines by T lymphocytes (Figure 5). Because these cytokines are upstream of the actual itch event and because they are not the only mediators of disease and pruritus, these medications can take several weeks to be fully effective. Studies have shown that the signs of canine AD can
be well controlled with the use of ciclosporin, 5 mg/kg every 24 hours, in approximately 50% to 70% of cases, with increasing percentages during longer-term use. Major advantages include the lack of steroid-related side effects, such as polyuria, polydipsia, weight gain, muscle weakness, and personality changes. The major disadvantage to the use of this drug is the cost, but that can be lessened with every-other-day or half-dose-daily therapy, which is attainable in 40% to 50% of cases.
Figure 5. Ciclosporin is a calcineurin inhibitor that suppresses the production of inflammatory cytokines by T lymphocytes. Because the cytokines are released above the actual itch event and because they are not the only mediators of disease and pruritus, medications can take several weeks to be fully effective.
Gastrointestinal side effects occur in approximately 15% to 40% of cases but are usually self-limiting and can be minimized by slowly building up to the full dose over 10 to 14 days, pre-treating with an antiemetic 2 hours before cyclosporin for the first 10 days, freezing the capsules,
or giving medication with food. Other less common
side effects include papillomatosis, hirsutism, gingival hyperplasia, tremors/neuropathies, secondary pyoderma, and lymphoplasmacytic dermatitis. Occasional hypoalbuminemia, urinary tract infections, and increased liver enzymes may be seen.
Janus Kinase Inhibitors (example: oclacitinib)
Oclacitinib (Apoquelâ– Zoetis) is a Janus kinase (JAK) inhibitor that is labeled for the control
of pruritus associated with allergic dermatitis and control
An Urban Experience
of atopic dermatitis in dogs at least 12 months of age. The mode of action is to bind to and block the activity
of the JAK enzyme attached to the cellular cytokine receptors that utilize the JAK1 enzyme. Most of the cytokines involved in allergic skin disease utilize these types of receptors (Figure 6). Oclacitinib has been shown to control itch and inflammation as well as oral prednisolone does in client-owned dogs with allergic skin disease due to fleas, food, contactants, or atopic dermatitis without many of the side effects associated with the administration of corticosteroids. Dogs administered prednisolone had an increase in adverse effects, most importantly an increase in liver enzymes.
In laboratory studies, oclacitinib is more rapid-acting (within 1 hour) than oral prednisolone or dexamethasone injections in laboratory beagles administered IL-31.
Figure 6. Oclacitinib is a Janus-kinase (JAK) inhibitor that is labeled for control of pruritus associated with allergic dermatitis and control
of atopic dermatitis in dogs at least 12 months of age. It binds to and blocks the activity of the JAK enzyme attached to the cellular cytokine receptors that utilize the enzyme.
Monoclonal Antibodies (example: Cytopointâ)
With new information on the role of interleukin-31 (IL-31) in dogs with atopic dermatitis, a caninized anti-cIL-31 monoclonal antibody has been developed (Cytopointâ– Zoetis). Whereas Apoquelâ works by binding and blocking the JAK enzyme used by a wide variety of cytokines, working after the cytokines bind the receptor, Cytopointâ neutralizes only the IL-31 cytokine before binding to the receptor (Figure 7). When a single injection of 2 mg/kg was administered to client-owned dogs
with atopic dermatitis, 82% of dogs experienced clinical success in reduction of pruritus (2 cm reduction on a 10 cm scale) by day 3. Thirty eight percent achieved 50% or greater reduction in dermatitis scores (as measured by the CADESI-03 severity scale) 14 days after administration of the antibody and 52% by day 42. Side effects were approximately equal between dogs administered the antibody or placebo.
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