Atopica®... Still a Good Choice in the Management of Canine Atopic Dermatitis

Andrew Rosenberg, DVM, DACVD, Animal Dermatology & Allergy Specialists, White Plains, New York, and Riverdale, New Jersey

ArticleSeptember 20174 min read
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Brought to you by Elanco Animal Health 

Canine atopic dermatitis (CAD) is one of the most common reasons owners bring their dogs to a veterinarian. This condition is defined as a genetically predisposed inflammatory and pruritic skin disease with characteristic clinical features typically associated with immunoglobulin E (IgE) antibodies directed against environmental allergens.1 CAD is considered a diagnosis of exclusion.

The initial step in the pathogenesis is a defective epidermal barrier that facilitates penetration of potential allergens and microbes. This is followed by a cutaneous inflammatory response characterized by erythema and pruritus. Additional secondary clinical signs include self-excoriation with subsequent secondary superficial pyoderma, Malassezia dermatitis, and/or otitis externa. Treatment goals should include reducing pruritus and inflammation, addressing the defective epidermal barrier, and modulating the abnormal immune response.

Pruritus Relief

Cyclosporine is a safe and effective medication for the long-term treatment of canine atopic dermatitis. It is also helpful at reducing proliferative tissue and inflammation in ear disease associated with atopic dermatitis. The main mechanism of action is calcineurin inhibition, which results in inhibition of IL-2 as well as T-cell activation. As a result, cyclosporine has anti-inflammatory effects as well as antipruritic effects. Cyclosporine has been used by veterinarians for over 20 years and has been licensed (Atopica® [cyclosporine capsules] USP Modified [Elanco]) for the treatment of CAD for over 10 years. In that time, it has shown wide, reproducible evidence of both its efficacy and its safety. A review of 727 dogs treated with cyclosporine showed that approximately one- to two-thirds of patients had a decrease in pruritus of 50% or higher in 4 to 8 weeks.2 

With cost of treatment a frequent client concern, two properties of cyclosporine merit consideration. First, the dosing frequency can be tapered. Second, cyclosporine is primarily metabolized by CYP3A enzymes, drugs that inhibit CYP3A (e.g., ketoconazole and other azole antifungals) producing dose-sparing effects when used concurrently. This can potentially reduce the dosage of cyclosporine required.3 The side effects of Atopica are well-known and generally resolve spontaneously or following dose modification or cessation of therapy. Gastrointestinal effects are the most common, typically reported in the first month of therapy. Administering capsules frozen can minimize these effects without affecting pharmacokinetics.4,5

While cyclosporine is effective at reducing pruritus in the long-term, it can take 2-4 weeks of therapy before a clinical benefit is seen. Additional therapeutic options for more immediate pruritus relief include glucocorticoids or newer alternatives such as lokivetmab and oclacitinib. The latter two drugs primarily target the pruritic cytokine IL-31 and are fast-acting. It should be noted that the relatively recent availability of these products limits our understanding of their potential side effects.

Antipuritic Agents for Use in CAD

Agent/Recommended Dose

Features

Considerations

Atopica® (cyclosporine, Elanco): 5 mg/kg/day until good response, then taper to lowest effective frequency

Anti-inflammatory

More than 12 years use, multiple publications, established safety profile

In many dogs dose frequency can be tapered

2-4 weeks to work

Gastrointestinal adverse effects when starting

Most side effects resolve spontaneously or following dose modification/cessation

Glucocorticoids: 0.5-1.0 mg/kg/day, tapered to every other day; equivalent dosing if other than prednisone or prednisolone

Fast-acting

Inexpensive

Anti-inflammatory

Long-term side effects

Apoquel® (oclacitinib, Zoetis): 0.4-0.6 mg/kg twice daily 14 days, then once daily

Fast-acting Inhibits a variety of pruritogenic cytokines and pro-inflammatory cytokines

Post-approval safety database limited to 4 years Not for dogs <12 months of age

Cytopoint™ (lokivetmab, Zoetis): 2 mg/kg every 4-8 weeks as a subcutaneous injection

Fast-acting

No specific labeled age requirement

Repeated injections

Further data needed to establish safety profile

Allergen-Specific Immunotherapy (ASIT): Protocols differ; based on individual patient

Only therapy to modify CAD pathogenesis

No long-term adverse effects

May prevent new allergies

May induce remission

Takes months to work

Requires allergen identification

See Important Safety Information below.

Therapies to Address Barrier Function and Infection

Defective epidermal barrier function should be addressed with topical therapies that can hydrate the skin, reduce allergen penetration, and decrease colonization by microorganisms. Bathing can remove irritants, decrease allergen load and pruritus, and both treat and help mitigate secondary infections. Effective shampoo ingredients include emollients, humectants, ceramides, and moisturizers. “Spot-on” products may help repair the epidermal barrier.

Secondary infections should be addressed or poor overall response is likely. Superior antibacterial efficacy makes chlorhexidine products excellent for CAD, with efficacy against StaphylococcusPseudomonas, and Malassezia spp.6 Mild infections can often be managed with topical therapies such as chlorhexidine-based shampoos, sprays, or mousses. In moderate to severe infections, systemic antimicrobial therapies are warranted. Ideally, therapy is based on cytologic evaluation through impression smears and/or cultures when warranted.

Immunotherapy

Allergen-specific immunotherapy (ASIT) is the only treatment that can modify or reverse CAD pathogenesis. Up to 80% of patients have good to excellent response, but clinical benefit can take 4 to 12 months.7 Other therapies are ideally used until ASIT becomes effective and then tapered to the lowest effective dose or discontinued. In some patients, Atopica can be tapered to every other day or less.