Targeted therapy for allergic dermatitis: just what the doctor ordered

Managing allergic dermatitis can be frustrating for veterinarians and owners alike. Diagnosis isn’t straightforward, as clinical signs for various types of allergic dermatitis (e.g., flea allergy, atopic dermatitis, food allergy) can overlap. Diagnosis of atopic dermatitis is generally based on consistent history, clinical signs and exclusion of other differentials.¹ However, reaching a definitive diagnosis isn’t always practical due to the associated cost and the steps involved in ruling out all other possible causes. Often, veterinarians must treat atopic and allergic dermatitis without the benefit of a confirmed diagnosis.

Selecting the best treatment for a specific patient presents its own challenges, as some therapies are ineffective and client compliance can be an issue. Fortunately, newer targeted treatments offer fast response times and good efficacy.

TRADITIONAL THERAPIES FOR ALLERGIC DERMATITIS

Glucocorticoids have been a mainstay for managing allergic dermatitis for a long time, but they have limitations. Although they effectively relieve itching and inflammation, the

side effects—primarily increased drinking, urination and appetite, as well as behavioral changes in some dogs—are intolerable for some pet owners.^2,3

Some veterinarians reach for antihistamines because they are inexpensive and associated with minimal side effects. However, antihistamine monotherapy is frequently ineffective. Simply blocking histamine is often inadequate because it is primarily the key cytokine mediators that are causing the pet’s itch and inflammation. According to the International Committee on Allergic Diseases of Animals, antihistamines offer little or no benefit in treating flares of canine atopic dermatitis.⁴ Also, antihistamines tend to cause drowsiness, which some pet owners find objectionable.

Inadequate treatments can prolong patient suffering and can contribute to owner dissatisfaction, disappointment and loss of confidence in the treatment process. Fortunately, veterinarians have newer options available, like targeted therapy.

WHAT IS TARGETED THERAPY, AND HOW IS IT DIFFERENT?

Newer targeted therapies work by inhibiting specific steps in the pathway that produces itching and inflammation in dogs with atopic and/or allergic dermatitis.

Cytokines are chemical signaling molecules that act as inflammatory mediators. Cytokines with a pivotal role in canine allergic dermatitis include interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-13 (IL-13) and interleukin-31 (IL-31).⁵ These cytokines contribute significantly to itching and inflammation in allergic dogs. For example, when IL-31 binds to sensory neuron receptors in the skin, it triggers JAK enzyme–mediated pathways that stimulate the itch signal.⁶

One targeted therapy, CYTOPOINT® (Zoetis), is an injectable, caninized monoclonal antibody that targets IL-31 specifically, stopping itching by inhibiting the binding of this cytokine to its receptors in dogs with allergic dermatitis and atopic dermatitis.^7,8

Oclacitinib tablet (APOQUEL®—Zoetis) is a targeted therapy that works fast and provides good efficacy in dogs with atopic dermatitis and allergic dermatitis. APOQUEL is a JAK enzyme inhibitor that selectively targets JAK-1–dependent pruritogenic, proallergic and pro-inflammatory cytokines.⁵ APOQUEL stops itching and inflammation at the source by suppressing transmission of chemical signals that lead to clinical signs in dogs with atopic and allergic dermatitis.

WHY CHOOSE APOQUEL?

Following oral dosing, APOQUEL starts to relieve allergic itch within 4 hours,⁹ significantly controls itch within 24 hours¹⁰ and, with continued use, relieves inflammation and improves skin lesions.^9,11

APOQUEL is safe and effective for short-term flare-ups or long-term therapy.^10,12 It can be used concurrently with NSAIDs, vaccines, allergen immunotherapy, antibiotics, parasiticides and antifungals.¹² The use of APOQUEL has not been evaluated in combination with glucocorticoids, cyclosporine or other systemic immunosuppressive agents. APOQUEL does not interfere with results of serum allergy testing or intradermal testing.¹³ APOQUEL is also easy for pet owners to use. It can be given with or without food,14 making dosing easier. And once-daily therapy (following initial twice-daily dosing up to 14 days)¹⁴ means better owner compliance.

In a short-term clinical study the most common adverse events were vomiting and diarrhea.¹⁰

EFFICACY STUDIES

APOQUEL’s efficacy for the treatment of atopic dermatitis was assessed in a multicenter, randomized, placebo-controlled trial involving 18 dermatology referral practices in the United States.¹¹

Dogs with atopic dermatitis received APOQUEL or placebo and were followed for 112 days. Treatment success was based on owner assessments of improvements in itching and veterinary dermatologists’ assessments of improvements in skin lesions. Dogs receiving APOQUEL improved significantly compared with dogs receiving placebo.¹¹

Although APOQUEL’s efficacy for atopic dermatitis has been well documented, dogs with other forms of allergic dermatitis also respond well. In a 30-day multicenter study,¹⁰ 436 dogs with atopic dermatitis, flea allergy dermatitis, food allergy, contact allergy or unspecified allergic dermatitis were given APOQUEL or a placebo and assessed for improvement in pruritus. After 7 days of treatment, 84.6% of dogs receiving APOQUEL had improved, compared with 42.5% of dogs given a placebo. Based on owner assessment, dogs receiving APOQUEL had lower mean pruritus scores on each of the seven evaluation days compared with dogs receiving a placebo. For dogs that continued receiving APOQUEL throughout the 30-day study, veterinarian-assessed dermatitis scores continued to improve until the end of the trial.¹⁰

THE BOTTOM LINE

Allergic itch isn’t just a nuisance. Itching is an urgent medical condition that needs fast and effective therapy. Itching can make pets and their owners miserable, which contributes to poor quality of life and adversely affects the human-animal bond. The good news is that targeted therapies, like APOQUEL, are making a difference and changing the lives of allergic dogs and their owners.

IMPORTANT SAFETY INFORMATION:

Do not use APOQUEL in dogs less than 12 months of age or those with serious infections. APOQUEL may increase the chances of developing serious infections, and may cause existing parasitic skin infestations or pre-existing cancers to get worse. APOQUEL has not been tested in dogs receiving some medications including some commonly used to treat skin conditions such as corticosteroids and cyclosporines. Do not use in breeding, pregnant, or lactating dogs. Most common side effects are vomiting and diarrhea. APOQUEL has been used safely with many common medications including parasiticides, antibiotics and vaccines. See Brief Summary of Prescribing Information in the PDF below.

REFERENCES

1. Gedon NKY, Mueller RS. Atopic dermatitis in cats and dogs: a difficult disease for animals and owners. Clin Transl Allergy. 2018;8:41.

2. Sousa CA. Glucocorticoids in veterinary dermatology. In: Bonagura JD, Twedt DC, eds. Kirk's Current Veterinary Therapy. 14th ed. St Louis, MO: Saunders Elsevier; 2009:400-404.

3. Notari L, Burman O, Mills D. Behavioural changes in dogs treated with corticosteroids. Physiol Behav. 2015;151:609-616.

4. Olivry T, DeBoer DJ, Favrot C, et al. Treatment of canine atopic dermatitis: 2015 updated guidelines jfrom the International Committee on Allergic Diseases of Animals (ICADA). BMC Vet Res. 2015;11:210.

5. Gonzales AJ, Bowman JW, Fici G, et al. Oclacitinib (APOQUEL®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy. J Vet Pharmacol Ther. 2014;37(4):317-324. doi:10.1111/jkm.12101

6. Gonzales AJ, Humphrey WR, Messamore JE, et al. Interleukin-31: its role in canine pruritus and naturally occurring canine atopic dermatitis. Vet Dermatol. 2013;24(1):48-e12.

7. Data on file. Study Report No. C166R-US-17-180, 2018, Zoetis Inc.

8. Souza CP, Rosychuk RAW, Contreras ET, et al. A retrospective analysis of the use of lokivetmab in the management of allergic pruritus in a referral population of 135 dogs in the western USA. Vet Dermatol. 2018;29(6):489-e164. doi:10.1111/vde.12682

9. Gadeyne C, Little P, King VL, et al. Efficacy of oclacitinib (APOQUEL®) compared with prednisolone for the control of pruritus and clinical signs associated with allergic dermatitis in client-owned dogs in Australia. Vet Dermatol. 2014;25(6):512-e86. doi:10.1111/vde.12166

10. Cosgrove SB, Wren JA, Cleaver DM, et al. Efficacy and safety of oclacitinib for the control of pruritus and associated skin lesions in dogs with canine allergic dermatitis. Vet Dermatol. 2013;24(5):479-e114. doi:10.1111/vde.12047

11. Cosgrove SB, Wren JA, Cleaver DM, et al. A blinded, randomized, placebo-controlled trial of the efficacy and safety of the Janus kinase inhibitor oclacitinib (APOQUEL®) in client-owned dogs with atopic dermatitis. Vet Dermatol. 2013;24(6):587-e142. doi:10.1111/vde.12088

12. Cosgrove SB, Cleaver DM, King VL, et al. Long-term compassionate use of oclacitinib in dogs with atopic and allergic skin disease: safety, efficacy and quality of life. Vet Dermatol. 2015;26(3):171-179. doi:10.1111/vde.12194

13. Aleo MM, Galvan EA, Fleck TJ, et al. Effects of oclacitinib and prednisolone on skin test sensitivity [abstract]. Vet Dermatol. 2013;24(3):297.

14. Apoquel (oclacitinib tablet) prescribing information. Zoetis. Published February 2013. Accessed June 16, 2020. zoetisus.com/products/dogs/apoquel/downloads/final_apoquel_

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