My clinical experience with Apoquel (oclacitinib), updated 11/1/16

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, 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:

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 2 cases, both collies, where they were able to have half or less their regular dose and do ok.

Apoquel works rapidly, most pets see complete relief within 2 days.  We typically give it twice daily for 7 days if the pet is very uncomfortable, then go to once daily.  If it has not worked after a week, it is very unlikely to work better with continued use in my opinion.  Zoetis reports that 60% of moderate to severe atopic dermatitis cases are controlled long term, likely because severe cases would do better on twice daily dosing.  It is rare that Apoquel controls pruritus in dogs whose allergies were so severe that they require daily steroids.

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.  The only possible interaction I have seen so far is with pets getting more sleepy than normal when Apoquel was given with Benadryl, possibly Temaril P, and these were individual cases. 

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.  Obviously a short transition 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.

Side Effects:

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, a few dogs developed polydipsia, increased appetite, and aggression, similar to what may be seen with steroids.

My Experiences:

I have started over 1000 dogs on Apoquel.  It is fairly 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 cases who had bone marrow suppression (other than zero allergy symptoms), only changes on bloodwork were discovered.  This is why we recommend bloodwork at the 2-3 month point after starting Apoquel.  In the rare cases I have seen, the bone marrow recovered after a few weeks of stopping Apoquel.  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.  Steroids and cyclosporine do not cause bone marrow suppression even at extreme doses, so this is one downside to Apoquel.  

Ear infections seem at an unusually high rate in my opinion, at least compared to what I have seen with steroids or cyclosporine- drugs which tend to prevent ear infections.  Sometimes we also see urinary tract infections while pets are on Apoquel, however, I am suspicious this type of infection is more common in patients who have allergies anyway.

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 prednisone.   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.  

Some dermatologists have used Apoquel in cats (desperate cases) with some success, however this use is not FDA approved, high doses are needed, and more than once daily dosing is needed.  I have not had luck with this drug in the handful of cats I have tried it on.

So far, I have not had Apoquel help with conditions other than allergic dermatitis in dogs.

We don’t know long term side effects of Apoquel in dogs, time will tell.  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 would recommend Apoquel over cyclosporine in a dog with previous cancer.  Comfort and quality of life are absolute considerations when deciding which medications to use.

Monitoring:

Our protocol for Apoquel 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.  Since we have not been monitoring urinalyses routinely, it is possible there are silent UTIs.

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, no withdrawal needed for skin testing, and decent price.  The downsides include:  increased infections, monitoring needed for bone marrow suppression, does not work for many pets, and we do not have long term data.  It is a wonderful option for those dogs who do not tolerate steroids or cyclosporine.  Allergy testing and shots remains the only effective management of allergies that does not involve immune suppression.

Monitor blood work prior to administering this medication (especially in older animals), at 3 months, and then annually thereafter until we have more information about long term use in dogs.  I do not recommend using this medication against the recommendations on the drug insert.

Report all adverse side effects to the company or to the FDA:  Link Here