Today's Veterinary Practice

JAN-FEB 2018

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55 JANUARY/FEBRUARY 2018 ‚óŹ TVPJOURNAL.COM CONTINUING EDUCATION Steroid-Sparing Agents Medications that may help avoid adverse effects associated with long-term systemic glucocorticoids are also available for dogs with CAD. Oclacitinib Oclacitinib (Apoquel, zoetis.com ) is the first Janus kinase (JAK) inhibitor approved in the United States and Canada for the treatment of atopic dermatitis in dogs. 37 JAKs are nonreceptor tyrosine kinases activated by various cytokine receptors and regulate the expression of multiple inflammatory genes. JAK inhibition may modulate the immune response to varying degrees, ranging from selective inhibition of cytokine production with anti-inflammatory effects to broader inhibition of cytokine production resulting in immunosuppression. Four JAK families of enzymes (JAK1, JAK2, JAK3, and tyrosine kinase 2) exist in mammals, and different inhibitors target different families. 38 At this time, oclacitinib is considered to be a selective JAK1 inhibitor, and as such it is proposed to be an anti-itch agent without being immunosuppressive. 38 However, safety studies performed in 6- and 12-month- old dogs with high oclacitinib dosages resulted in adverse effects, suggesting that this drug has potential immunosuppressive properties in dogs (US Food and Drug Administration [FDA] data 39 ). A recent study used an integrated modeling approach using isolated canine T cells; the results revealed that oclacitinib appears to have immunosuppressive properties, but only at dosages above those used to treat allergic pruritus in dogs. 40 Oclacitinib (0.4 to 0.6 mg/kg q12h for 14 days, then q24h as needed) is considered a safe, fast-acting, well-tolerated oral drug with good efficacy for inducing remission and long-term control of CAD in dogs at least 12 months old. It has a very rapid onset of action for itch and a slower one for skin inflammation. Its immunosuppressive properties during in vivo administration are unknown, and opportunistic infections (eg, viral papillomas) or infestations (eg, demodicosis) might develop in susceptible individuals. In these cases, oclacitinib should be discontinued until the infection/infestation clears or is treated adequately; other anti-itch/inflammation drugs may be used for control of CAD in these patients. Two recent studies indicated that routine hematologic evaluation, serum chemistry, and urine culture are not indicated for dogs receiving oclacitinib up to 630 days; however, clinicians should decide on monitoring in each case on the basis of clinical signs. 37,41 Cyclosporine Oral cyclosporine is a calcineurin inhibitor that, at low doses, exerts an anti-inflammatory and immunomodulatory effect through inhibition of T-cell activation. 42 Cyclosporine is approved for the long- term control of CAD at the starting oral dose of 5 mg/kg q24h for at least 6 to 8 weeks because clinical benefit has slow onset; the full benefit of this drug is usually observed after 8 weeks of administration. 1,3,43 Oral steroids 43 or oclacitinib 44 can be administered concurrently in the first 3 to 4 weeks to overcome the slow onset of clinical effect; a recent study showed that the administration of oral prednisolone (1 mg/kg q24h for 7 days then q48h for 14 days) with cyclosporine at 5 mg/kg led to a rapid reduction in pruritus and skin lesions. In patients with good response to cyclosporine, the long-term dose and/ or frequency are adjusted as needed for therapeutic effect. Vomiting and diarrhea are seen in 30% of patients but are usually self-limiting within the first 7 to 10 days; administration with food or freezing the cyclosporine capsules may help decrease gastrointestinal upset. 42 As with many immunosuppressive drugs, opportunistic infections (eg, fungal infections) may develop in susceptible individuals receiving cyclosporine. 45 A retrospective study evaluated the frequency of urinary tract infection and recommended routine urine cultures for dogs receiving long-term cyclosporine; however, some dogs in this study may have had subclinical infections before cyclosporine administration. 46 Less commonly reported dermatologic adverse effects include gingival hyperplasia, psoriasiform- lichenoid-like dermatitis, and hyperplastic verrucous lesions. 42 These effects usually regress with dose tapering and/or discontinuation of the cyclosporine. Monitoring of cyclosporine levels during treatment of CAD is difficult because no significant correlation has been found between positive clinical improvement and cyclosporine blood concentration in atopic dogs; clinical response to cyclosporine remains the most reliable method of assessing efficacy in CAD. 47 Microemulsified cyclosporine (Atopica, elanco.com ) is approved for use in dogs with CAD in the United States; the formulation of Atopica is identical to the human formulation, Neoral ( pharma.us.novartis.com ). 42 A human generic ultramicronized emulsified cyclosporine (Equoral, tevatxteam.com ) was shown to be as effective as prednisone in reducing skin lesions and pruritus in atopic dogs, 48 whereas a new

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