Atopic dermatitis & Oclacitinib(Apoquel®)

This posting is NOT a professional article to provide veterinary clinical advice and consultation.

Also, this is not for the promotion of specific veterinary drugs/medicines.

This posting is just for the purpose of studying summarised by a veterinary medicine student.

If there is anything that needs to be corrected, please comment to this posting :)

이 글은 수의대 학생 신분으로 작성한 포스팅으로, 공부 목적으로 배운 것과 리서치 한것을 종합하여 요약한 것입니다.

 

 

 

1. Atopic dermatitis?

Atopic dermatitis is a hypersensitive reaction or over-reaction to the specific allergens causing itchiness(pruritis).  

It is chronic relapsing genetically predisposed inflammatory and pruritic allergic skin disease with characteristic clinical features that are associated with IgE antibodies, most commonly directed against environmental allergens such as plant pollens, house dust mites or mould spores. It appears to be more common in dogs than in cats.

Golden Retrievers, Labrador Retrievers, West Highland White Terriers and other terriers, and Bulldogs are major breeds that are predisposed to allergies.

 

The first step involved in the development of AD is sensitization to environmental allergens mainly penetrating through the skin able to lead to recruitment inflammatory cells and degranulation of mast cells by binding to IgE. On activation, multiple inflammatory mediators, including cytokines and chemokines are secreted.

 

*Clinical signs

Itchiness, scratching, rubbing, chewing areas of the body. 

It involves mostly the face, axillae, ventral neck, ventral abdomen, inguinal area, and feet (mostly interdigital areas).

 

*Treatment options(drugs)

• Antihistamines (amitriptyline hydrochloride, cetirizine hydrochloride, chlorpheniramine maleate, clemastine fumarate, cyproheptadine hydrochloride, diphenhydramine hydrochloride, doxepin hydrochloride, fexofenadine hydrochloride, hydroxyzine hydrochloride, loratadine, trimeprazine + prednisolone) – topical, oral

• Ceramides – topical

• Colloidal oatmeal – topical

• Cyclosporine – oral

• Essential fatty acids – oral, topical

• Glucocorticoids (betamethasone, dexamethasone, hydrocortisone, hydrocortisone aceponate, isoflupredone acetate, methylprednisolone, mometasone furoate, prednisolone, prednisone, triamcinolone acetonide) – topical, oral, injectable (cats only)

• Interferon-gamma, recombinant canine – injectable

• Interferon-omega, recombinant feline – injectable

• Masitinib mesylate – oral

• Neutralized zinc – topical

• Misoprostol – oral

• Pentoxifylline – oral

• Phytosphingosine salicyloyl – topical

• Pimecrolimus – topical

• PO7P (Chinese herbal supplement) – oral

• Pramoxine hydrochloride – topical

• Tacrolimus – topical

• Source: Canine and Feline Dermatology drug handbook(Willy-Blackwell, Sandra N.Koch, Sheila M.F.Torres and Donald C.Plumb)

 

Drug therapy aimed at inhibiting mast cell mediator production and at blocking or counteracting the effects of released mediators. Anti-inflammatory agents (eg. corticosteroids or antihistamines)

 

In terms of corticosteroids(synthetic glucocorticoids), it has anti-inflammatory by inhibiting phospholipase A2 and reducing expression of COX-2(inducible form). It also suppresses mast cell degranulation and cytokine-induced proliferation of mast cells.

Mast cells play an important role in immediate hypersensitivity as a major effector cell through the activation via the high-affinity IgE receptor, Fc epsilon RI.

It has a very rapid onset and needs just several hours to take effects of the drug.

However, side effects are common, so it is important for vets to consider well when prescribing glucocorticoids.

 

In terms of antihistamine, specifically H1 antihistamine, it inhibits itch sensation by prevention of sensory nerve stimulation. H1 post-synaptic receptors stimulate sensory nerves to cause itch

 

2. Oclacitinib(Apoquel®)

- Synthetic Janus Kinase(JAK) inhibitor

- Inhibition of JAK1-dependent cytokine signalling involved in allergy and inflammation (IL-2, IL-4, IL-6, and IL-13) as well as pruritus (IL-31)

- JAK enzymes play a key role in transmitting signals of cytokines. Oclacitinib inhibits JAK family members effectively.

Oclacitinib also inhibits the function of various pruritogenic cytokines and pro-inflammatory cytokines, as well as cytokines involved in allergy.

 

 

 

 

Reference/sources/further reading

1. Veterinary Partner https://veterinarypartner.vin.com/default.aspx?pid=19239&id=4951973

Atopic Dermatitis in Dogs - Veterinary Partner - VIN

2. Textbook - Canine and Feline Dermatology drug handbook(Willy-Blackwell, Sandra N.Koch, Sheila M.F.Torres and Donald C.Plumb)

3. Oclacitinib (APOQUEL) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy- 

J. vet. Pharmacol. Therap. 37, 317--324. doi: 10.1111/jvp.12101. retrieved 8/7/2020

4. 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, DOI: 10.1111/vde.12166, retrieved 8/7/2020

5. APOQUEL® (oclacitinib tablet): Fast-Acting and Safe Itch Relief So Your Dog and You Can Return to Normal, Zoetis information sheet.

6. Domenico Santoro, Therapies in Canine Atopic Dermatitis: An Update, Vet Clin Small Anim 49 (2019) 9–26 https://doi.org/10.1016/j.cvsm.2018.08.002