My clinical experience with Apoquel® (oclacitinib), updated 1/31/2023

Dr. Melissa Eisenschenk, DVM, DACVD

Apoquel® is the brand name of oclacitinib, an FDA approved immune suppressant drug in the Janus Kinase (JAK) inhibitor class made by Zoetis. This drug inhibits primarily JAK-1 and -3 signaling that would normally occur when a cytokine binds to a receptor on the surface of the cell. This includes blocking the effects of inflammatory cytokines released from activated lymphocytes (IL-2, -4, -6, -13) as well as IL-31, a cytokine directly involved in the sensation of itch. JAK signaling is important to the function of the bone marrow as well. Apoquel works differently than steroids, antihistamines, Cytopoint, or cyclosporine.

Apoquel works rapidly, usually within 24 hours, to diminish itching. It is very rare to have GI upsets with Apoquel like we can see with cyclosporine. The antipruritic effects of the Apoquel wear off quickly, within 12-24 hours, so the medication needs to be given daily in most cases.

Dosing/Administration for dogs:

The dose of Apoquel is 0.4-0.6 mg/kg every 12 hours for up to 14 days, then 0.4-0.6 mg/kg once daily thereafter. Apoquel is not FDA approved to use twice daily longer than 14 days. The dose range is very strict, I do not recommend going above the recommended dose due to immune suppression, below the range and it doesn’t seem to work in most cases. I have seen some mild cases that are managed with lower doses.

Apoquel works rapidly, most dogs see complete relief within just a few days. Infections with yeast, bacteria, or mites may prevent apoquel from working as well as it should. Zoetis reports that 60% of moderate to severe atopic dermatitis cases are controlled long term at once daily dosing, some severe cases may do better on twice daily dosing long term, but this is off label use (not FDA approved). Most moderate to severe skin diseases need combinations of several therapies to keep the patient well controlled.

In humans, it is not recommended to give some of these JAK inhibitor drugs with CYP3A4 inhibitors like ketoconazole. I have not seen bad side effects giving almost any drug with Apoquel, including ketoconazole. I recommend using caution with other drugs that may affect the bone marrow however.

Long term studies of giving Apoquel along with other immunosuppressants like steroids and cyclosporine have not been done. My clinical experience would suggest that steroids at anti-inflammatory doses of 0.5mg/kg twice daily and taper is seems to be safe for the short term. If steroids are needed with Apoquel, evaluate how well the Apoquel is actually working for the patient. Apoquel is effective very quickly, so there is no need to transition slowly from steroids to Apoquel. Tapering steroids may be needed to prevent an Addisonian crisis in a pet who has been on high doses or daily steroids for more than a month.

Apoquel is only FDA approved for dogs who are greater than 12 months of age. The reason for this is that below 1 year of age, demodicosis and pneumonia were seen at an unacceptable level when Apoquel was given at 3 x and 5 x the regular dose. In my clinical experience, Apoquel just does not seem to work well in young puppies for allergies anyway.

Side Effects in Dogs:

Other drugs in the same drug class as Apoquel include drugs for humans for rheumatoid arthritis, psoriasis, and cancer. In humans, the side effects of drugs in the JAK inhibitor class of drugs include: neutropenia, anemia, thrombocytopenia, increased liver values, increased cholesterol, UTI, weight gain, herpes zoster.

Apoquel side effects listed for dogs in the product insert include: vomiting, diarrhea, lethargy, anorexia, SQ or dermal masses (unspecified), decreased leukocytes, decreased globulins, and increased cholesterol and lipase. Low numbers of dogs in the studies developed demodicosis, neoplasia, pneumonia, bloody diarrhea, skin and ear infections, UTIs, and histiocytomas.

Interestingly, in early studies, a few dogs developed polydipsia, increased appetite, and aggression, similar to what may be seen with steroids- I have not seen these issues with a proven link to Apoquel.

My Experiences:

I have started over 1000 dogs on Apoquel. It is rare to see side effects while a pet is on Apoquel. Bone marrow suppression is the most concerning side effect, but we have only seen this in about 1% of pets on Apoquel. No outward signs were seen in these dogs who had bone marrow suppression, only changes on bloodwork were discovered. This is why we recommend bloodwork at the 2-3 month point after starting Apoquel in dogs. After decreasing the dose of Apoquel, the bone marrow recovered rapidly, within a few weeks. Even in cases where the CBC values do not go below normal, it is common for the values to sink towards the low end, the clinical significance of this is not known. Other atopic dermatitis medications (Cytopoint, Atopica) do not cause bone marrow suppression even at extreme doses. Allergy testing and shots remains the only management of allergies that does not involve some type of immune suppression, but may take a long time to work or not work at all. Some dogs with atopic dermatitis do not have allergies.

Ear infections are not controlled with Apoquel as well as they are controlled with steroids or cyclosporine. Sometimes we also see urinary tract infections while pets are on Apoquel, however, I am suspicious urinary tract infections are more common in patients who have atopic dermatitis and not related to the Apoquel.

Similarly to the side effect of weight gain seen in humans on JAK inhibitors, I have seen weight gain in dogs on Apoquel, not to the degree seen with steroids. I have not had owners report an increased appetite. Perhaps they are getting less exercise from not scratching as much. It would be nice to perform a study with normal dogs, who (like humans) may tend to gain weight over time no matter what drugs they are on.

Very rare dogs have become manic on Apoquel- the owners say the dogs have a “funny look on their face” and run around the house and can’t settle down. I have seen 2 of these cases and really can’t explain how Apoquel would cause this- perhaps there were other drugs involved. This condition resolved when the Apoquel was stopped.

Interestingly, I have seen Apoquel improve mobility in dogs with arthritis. I am not sure if this is just because they overall “feel better” when their skin is not inflamed or if some dogs with allergic inflammation of the skin also have inflammation of the joints as well. It is common for me to hear a dog "acts like a puppy again!" after starting Apoquel.

It doesn't appear there are long term side effects of Apoquel use in dogs, at least no studies have shown any concerning issues so far. The product insert warns of "unspecified skin masses" when using Apoquel. Histiocytomas are more common in dogs on Apoquel, they are also more common in dogs with atopic dermatitis and typically resolve on their own, rarely requiring surgical removal. Stopping Apoquel may allow histiocytomas to resolve faster, there are no studies on this. Viral papillomas can be worse in dogs on Apoquel. Viral papillomas are caught from other dogs and usually resolve on their own, but stopping Apoquel may help viral papillomas resolve faster. Always have your vet evaluate any masses on your dog.

The product insert warns that Apoquel may exacerbate neoplastic conditions. There is no good evidence of this as of yet, we will keep monitoring. I often see terrible skin disease in dogs caused by an internal disease like cancer, so keep in mind that many of the internet reports of "I started my dog on Apoquel and he immediately got cancer/died" are, in my experience, likely to be dogs with skin itchiness and infection of that was triggered by an internal disease or cancer, and they were treated with Apoquel to try to help symptoms, before the underlying cause of the skin disease was determined. Comfort and quality of life are always considerations when deciding which medications to use for a pet with a history of cancer or other internal disease.

Monitoring:

Our protocol for Apoquel monitoring in dogs who are on once daily dosing is to check a CBC/Chem6 prior to starting Apoquel, then at 3 months, then once yearly. The CBC is the most important piece of information for monitoring. It is important to make sure the dog does not have liver disease prior to starting the Apoquel. The only exception to this would be liver elevations caused by steroids. Time will tell if urine monitoring is important- I do not monitor urine samples.

Summary:

I like Apoquel. The benefits of Apoquel include: rapid onset of action, low likelihood of GI side effects, rare side effects with long term use. The downsides include: monitoring needed for bone marrow suppression, does not work for some pets, and we do not have much long term data. It is a wonderful option for most dogs with atopic dermatitis.

Monitor blood work (CBC, Chemistry) prior to administering this medication (especially in older animals), at 3 months, and then annually thereafter. Read the drug insert for more information and FDA recommended use.

Report all adverse side effects to the FDA or to the company Zoetis: Monday, Tuesday, Wednesday, and Friday 8:30 AM - 7:00 PM EST, and Thursday 9:30 AM-7:00 PM EST at 1-888-963-8471

If you have questions about Apoquel, please contact your veterinarian or call ZOETIS at 1-888-963-8471 as we cannot give medical advice for patients we have not seen at our clinic.

Apoquel Use in Cats:

Apoquel can be used in cats to manage atopic dermatitis and other immune mediated diseases, however this use is not FDA approved. Higher doses are needed for cats compared with dogs, and more than once daily dosing is often needed. Some cats respond well to this therapy, others do not respond at all. We monitor bloodwork on all cat patients on Apoquel at 2 months, 5 months, and every 6 months. After review of 166 cats started on Apoquel, 66% of cats were well controlled, however, within 2-5 months 7% of those controlled cats had to stop Apoquel due to low immune cell counts (neutropenia). Apoquel did not work for 34% (57 cats), some cats would not take the medication (3), some had vomiting (6), some had diarrhea (4), and some were lethargic (2). Most just did not see improvement in symptoms after a 1 month trial. Due to potential side effects of using this medication off label, I recommend a veterinary dermatologist manage feline cases that need to use Apoquel.