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Atopic Dermatitis in Dogs - Oclacitinib to Control Pruritus

  • December 17, 2015 11:18 AM EST

    This week's Evidence Based Update is a discussion on the use of oclacitinib in dogs with allergic dermatitis, including data from a recently published study on the safety and effects of long-term compassionate use of oclacitinib in dogs.

    Atopic Dermatitis

    The etiology and pathogenesis of atopic dermatitis (AD) is complex and involves a genetic predisposition and immunologic abnormalities along with an impairment of normal skin-barrier function caused by microorganisms, pollen, and abnormal lipid lamellar formation. This pruritic, inflammatory skin condition is associated with the development of IgE antibodies to environmental allergens. AD can be difficult to diagnose because clinical presentation varies depending on the extent of lesions, genetic (breed-associated) factors, presence of microbial infection, stage of disease, and similarities to other skin conditions unrelated to AD. Pruritic skin disease that has the characteristics of AD in the absence of a positive IgE test is called atopic-like dermatitis (ALD).

    The cytokine, interleukin-31 (IL-31) has recently been shown to play a role in pruritic skin conditions in humans. Canine IL-31 (cIL-31) has been detected in freshly isolated canine peripheral blood mononuclear cells. When IL-31 binds to a receptor complex (IL-31 receptor A and oncostatin M receptor beta) signal transduction cascades eg, as the Janus kinase–signal transducer and activator of transcription (JAK–STAT), mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are activated.

    Pruritic allergic skin disease is common in both canine and feline populations, and its presentation is similar in both. Broadly, diagnosis relies on the combination of 3 approaches: (1) ruling out other skin conditions whose signs overlap with AD; (2) thorough review and interpretation of histologic and clinical features; and (3) allergy testing for detection of IgE.

    Newer criteria scales developed by Favrot and colleagues are useful tools for diagnosing canine AD.

    Favrot's Clinical Features of Canine Atopic Dermatitis
    Presence of at least 5 criteria:

    • Age of onset < 3 years
    • Lives indoors
    • Pruritus without lesions at onset
    • Front feet affected
    • Ear pinnae affected
    • Ear margins not affected
    • Dorsolumbar area not affected

    Treating Allergic Dermatitis

    Regardless of the evolving terminology, the practices of managing pruritic skin disease in cats and dogs are similar; the primary goal is to minimize the presence of pruritus and resolve associated skin lesions.

    There is no cure for AD or ALD and management depends on severity and whether pruritis is present seasonally or year round. Most of the data on disease management is in dogs with considerably less in cats, thus more trials are needed in the feline population. Treatment of signs includes the use of antipruritic drugs and control of secondary infections through:

    • Avoidance of allergens (dogs/cats): Can be impractical unless a specific allergen can be identified.

    • Relief from pruritus (dogs/cats): Relieve itching with antipruritic drug monotherapy or in combination with allergen-specific immunotherapy. Antihistamines are helpful but not consistently effective.

    • Bathing and coat hygiene (dogs/cats): Shampoo therapy may alleviate itching. Antimicrobial shampoos to treat / prevent microbial overgrowth or lipid-containing shampoos can be of benefit. Thus far there is little evidence to support the sole use of shampoos and conditioners that contain oatmeal, antihistamines, corticosteroids, or pramoxine to control pruritus, however they can be helpful when used adjunctively with other forms of treatment.

    • Recognition and control of flare factors (dogs/cats): A relapse of clinical signs in animals that are usually well controlled warrants investigation into flare factors (eg, coat hygiene, allergens, microbial overgrowth, diet, fleas) before using systemic antipruritic drugs.

    • Acute flares (dogs/cats): Allergic otitis is often seen in dogs, and topical otic corticosteroids may be adequate. For local pruritis in dogs and cats, a short course of a topical triamcinolone or hydrocortisone aceponate spray is supported. Oral steroids (prednisone, prednisolone, methylprednisone) may be needed for extensive, severe pruritis in dogs and cats until signs resolve.

    • Allergen-specific immunotherapy (dogs/cats): Hyposensitization to positive environmental allergens is often the method chosen by most veterinary dermatologists and allergists, especially in animals that have signs lasting for several months. In cats, intradermal test results are more difficult to read because the reactions are less marked than in dogs. After administration, increased pruritis can result from the higher levels of IgE; this resolves usually when the amount of allergen is reduced. It's important to note that a reduction of IgE does not always translate into clinical improvement. Immunotherapy is a long-term commitment for the owner and the veterinarian. Owners are cautioned to not expect much response for the first 6 months and should commit to at least a year of therapy.

    • Use of antipruritic drugs for chronic AD (dogs/cats): Essential fatty acids alone aren't enough to reduce pruritis. Response with cyclosporine in both dogs and cats is similar to that for glucocorticoids, with fewer adverse effects when given at recommended doses. Tacrolimus ointment has shown benefit for localized lesions. A newer approved drug for canine pruritis, the Janus kinase inhibitor oclacitinib, has been shown to be a rapid, effective and safe option. It specifically inhibits the expression of IL-31 and appears to have a rapid onset of action.

    Oclacitinib (commercially available as Apoquel) is approved for use in dogs to treat pruritus and inflammation associated with allergic dermatitis. Initial clinical trials demonstrated the short-term use safety profile for the drug. Until recently, the effects and safety of long-term use of the drug were unspecified. This week's Evidence Based Update reveals the findings of a recently published study on the effects and safety associated with the long-term use of oclacitinib in dogs including:

    - The effects and safety of oclacitinib with long-term use in dogs
    - Recommended dosing of oclacitinib in dogs
    - Expected side effects / tolerability
    - Recommended monitoring of patients
    - Impact on the quality of life of dogs with allergic skin disease

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