Oclacitinib (Apoquel®, Zoetis) is a Janus kinase inhibitor labeled and used for the treatment of allergic pruritus and atopic dermatitis in dogs, but it has not been evaluated for its clinical effectiveness and safety in cats. The Janus kinases (JAKs) are enzymes that play a crucial role in cytokine signaling; JAK1 and JAK3 are involved in the signaling of numerous cytokines involved in allergy and inflammation, including interleukins (ILs) 2, 4, 6, 13, and 31. Interleukin-31 is a known major mediator of canine pruritus, and oclacitinib blocks the action of IL-31 as well as ILs-2,4,6, and 13. Cytokines involved in hematopoeisis are dependent on signaling associated with JAK2, and oclacitinib has little effect on these when given according to the labeled dosing instructions: twice daily for up to 14 days and once daily thereafter. Previous studies concerning the use of oclacitinib in cats were limited to experimentally induced asthma and one case of a cat with mastocytosis that was successfully treated with the drug.
The present study, a small pilot study of 12 client-owned cats, was designed to evaluate the response to and safety of oclacitinib in cats with nonflea-, nonfood-induced hypersensitivity dermatitis (NFNFIHD). Oclacitinib is not labeled for juvenile animals; as dogs less than 12 months of age incur a high risk of demodicosis and pneumonia when treated with the drug, all study cats were over 12 months of age and greater than 3 kg in body weight. All cats were spayed or neutered; 8 were mixed breed, and 4 represented different popular feline breeds. Cats found to have ectoparasitic infestations or bacterial, fungal, feline immunodeficiency virus, or feline leukemia virus infections were excluded from the study. Five of the study cats were tested for toxoplasmosis IgG and IgM titers, and all were negative. Ten of the 12 cats enrolled in the study had a complete blood count and biochemical panel done prior to the oclacitinib therapy, and these blood tests were within normal limits on all animals tested. During the course of the study, the subjects were not permitted to eat raw meat and were not allowed outdoors.
Oclacitinib was administered twice daily to the study cats at a mean dose of 0.47 mg/kg (range, 0.42-0.56 mg/kg) PO for two weeks, then once daily at the same dose for two more weeks. This dosing range was based on that recommended for the dog and used in experimental studies in cats. Eleven of the 12 owners rated ease of administration of the medication as excellent, and the twelfth owner stated that ease of administration was good. Efficacy of the medication was rated as good to excellent by 4 of the 12 owners, fair by 3, and poor by 5. No adverse effects were recorded.
The reasons why some cats responded to the oclacitinib therapy and demonstrated relief of pruritus and clinical signs associated with allergy and some did not were not clear. No obvious correlation was found between the outcome and lesion type or severity, dose administered, or any other variable. More favorable results with treatment of feline NFNFIHD are obtained with use of cyclosporine or corticosteroids than with those obtained using oclacitinib in this study, which were comparable with positive results reported with the use of essential fatty acids and antihistamines. This was a small study and the use of a larger number of cats in a controlled study, possibly a higher dose of the drug, or a different dosing regimen might yield more encouraging results regarding the responsiveness of cats with NFNFIHD to treatment with oclacitinib. Oclacitinib may be a useful alternative in the treatment of NFNFIHD in cats in which corticosteroids are contraindicated or when oral administration of other drugs is difficult or causes adverse effects.
As the use of oclacitinib, an immunomodulating drug, is completely off-label in felines, it is vitally important to obtain the informed consent of the owner. In addition, assiduous monitoring of response to the medication and any potential adverse effects is essential. Oclacitinib is a new pharmaceutical, so the safety of long-term therapy is unknown. Pre-treatment laboratory evaluation as well as monitoring with complete blood counts and biochemical profiles on a regular basis is prudent. The safety of concurrent use of oclacitinib with other immunosuppressive or immunomodulatory drugs such as corticosteroids or cyclosporine has not been documented, and is not recommended. Both owners and clinicians should also be aware that it is unknown if there is an increased risk of neoplasia or infection with use of oclacitinib. The package insert states that oclacitinib may exacerbate neoplastic conditions. Behavioral changes, especially aggression, have been noted in a small number of canine patients receiving the drug; a larger study of oclacitinib use in cats might elucidate whether or not this is a potential problem in this species. [PJS]