Apoquel is a drug created by Zoetis for dogs with atopic and allergic dermatitis. Its main claim to fame is the unique way of stopping inflammation and allergic reactions by altering the immune system. It’s approved by the FDA for use in dogs and is currently the only drug in veterinary medicine with this mode of action. Many dogs are put on this medication to alleviate their dermatitis symptoms, mainly severe itching. Should the drug help, the dog might need to stay on it for a long time. But how safe is that?

From Zoetis being reprimanded by the FDA for minimizing Apoquel’s risks, to numerous studies showing a strong link to cancer, Apoquel clearly has a dark side. Many dog owners discovered that on their own … when it was already too late. If you’re still on the fence about Apoquel for dogs, this article shares FOUR hard truths about the long-term use of Apoquel that every dog owner should know! 

1 — Apoquel Modulates the Immune System

Apoquel for dogs works by interfering with the immune system, which is why it’s classified by the FDA as an immunomodulator. The immune system is the backbone of any healthy organism. Once it’s unstable, we are looking at a grim health prognosis for our dogs. Both allergic and atopic dermatitis are caused by an overactive immune system, which is likely why Zoetis chose this mode of action for Apoquel. That said, the immune system is a complicated network of cells and proteins that all serve multiple functions!

The interactions between JAK enzymes and cytokines play an important role in the immune responses, including allergic reactions. Think of cytokines as crucial messengers between the cells of the entire immune system. JAK (Janus kinase) enzymes decide which messages get transmitted. Oclacitinib, Apoquel’s active ingredient, inhibits the JAK enzymes (namely JAK1 and JAK3) and so suppresses several important JAK-dependent cytokines. 

Those suppressed cytokines are interleukins IL-2, IL-4, IL-6, IL-13, and IL-31. IL-2 regulates special white blood cells responsible for recognizing and eliminating sick cells in the body, including cancerous cells! IL-4 stimulates cells that produce antibodies important for fighting off bacteria and viruses. IL-6 is an inflammatory cytokine — when dysregulated, it can result in multiple diseases, including autoimmune disease, cancer, and neurological conditions. IL-13 plays a role in allergic inflammation, similar to IL-31, which sends a signal for itching. It’s clear that most of these interleukins play a much bigger role than just allergic inflammation, so interfering with them is a dangerous thing. 

Oclacitinib suppresses the immune system in a targeted way, not a broad way. This makes sense, as Apoquel targets very specific proteins in the immune system. It is not a comforting thought, though. Apoquel doesn’t have to broadly suppress the immune system because the targeted suppression already comes with great risk — especially when considering long-term use! It’s crucial that you ask yourself which parts of the immune system are targeted by oclacitinib? And what would happen if your dog’s cytokines suddenly couldn’t attack cancerous cells anymore or fight off bacteria? 

The role of the immune system is to protect the organism from the inside out. If you mess with a dog’s immune system, you mess with their inner biological protection.

2 — Research Consistently Shows a Link Between Apoquel and Cancer 

Apoquel’s package insert contains a lot of information about cancer. Under Warnings, it’s disclosed that Apoquel can worsen the state of pre-existing cancer conditions AND that “new neoplastic conditions (benign and malignant) were observed in dogs treated with Apoquel during clinical studies and have been reported in the post-approval period.” So, right from the very top of the package insert, the link with cancer is made clear. 

Under Adverse reactions, they cite several studies they’ve done during the clinical trials. One study that gave Apoquel to 283 dogs saw two dogs euthanized because of cancer. One of the dogs developed a cancerous mass at the heart base after only 21 days of taking Apoquel, while the other one developed a Grade 3 tumor after 60 days of taking Apoquel. A different study included 239 dogs and looked at the long-term Apoquel use. The dogs were on Apoquel for up to 610 days, 372 days on average. The results of this study are shocking: 

• Six dogs were euthanized because of “suspected” cancer in the chest, abdomen, spleen, sinuses, brain, and the bladder. The cancers were found after 17, 49, 120, 141, 175, and 286 days on Apoquel. 
• Another dog was euthanized due to fluid buildup in the abdomen and lungs after 450 days on Apoquel. 
• Two dogs developed a Grade 2 tumor after 52 and 91 days.
• One dog developed blood cancer after 392 days.
• Two dogs developed cancer in the anal glands after 210 and 320 days. 
• One dog developed oral cancer after 320 days.

It’s incredible that Zoetis looked at these results and still decided to put the drug on the market. It’s worrying to see how many different types of cancer were diagnosed, some of which are considered extremely rare, so it’s interesting how they all appeared in this one study with a relatively small population. Note how most of the cancers appeared after 100 or even 200 days! The longer the dogs were on Apoquel, the more malignancies were observed.

If those are the numbers displayed on the package insert, how bad are the numbers when other research is done? A study published in 2020 (though still with ties to Zoetis) looked at medical records of 660 dogs from four veterinary dermatology specialty clinics. Out of 339 dogs who received Apoquel, 67 dogs (that’s 16.5%) developed malignancies: 

• 13 dogs had mast cell tumors 
• 6 dogs had non-cutaneous lymphoma
• 6 dogs had soft tissue sarcoma (cancer in the soft tissue) 
• 5 dogs had a brain tumor
• 5 dogs had unspecified cancers

Now that Apoquel has been on the market for a decade, these numbers have turned into personal stories. Thousands of dog owners who put their dogs on Apoquel and then lost them to cancer are sharing their stories in Facebook groups especially dedicated to raising awareness about this issue. 

3 — The FDA Reprimanded Zoetis for Minimizing the Risks Associated With Apoquel

In 2018, the FDA’s Center for Veterinary Medicine issued a warning letter to Zoetis regarding their use of the word “safe” when advertising Apoquel on their website. This letter is one of the best representations of Apoquel’s risks and Zoetis’ desire to downplay and conceal them. The letter reads, in part: 

“This website makes false or misleading representations about the risks associated with APOQUEL.[…] They misleadingly minimize the risk associated with the use of APOQUEL by citing a short term study to support the claim that the side effects are minimal and were similar to placebo when a higher frequency of adverse reactions in Apoquel treated dogs was seen in a long term study. […] the website’s representation of APOQUEL as having “minimal side effects,” as being “similar to placebo without many of the side effects associated with the use of steroids,” and as “safe for use with many other drugs, including…allergen-specific immunotherapy” contradicts the important safety information and the risks associated with the use of APOQUEL.”

I highly recommend that you read the full letter right here! 

The FDA classified this offense as misbranding, taking a big issue with how Zoetis was misrepresenting the safety of Apoquel and even using short-term studies to manipulate the public into believing Apoquel was the safest option! The studies Zoetis cited on their website were their own studies, the studies they paid for … and still, they had to misrepresent the results to make their product look safer than it actually is. The FDA saw right through them, and they were correct — there really is a much higher frequency of adverse effects associated with Apoquel use, even outside of cancer.

The most commonly reported dermatological adverse effects are: pyoderma, non-specified dermal lumps, histiocytoma (benign skin tumors), yeast skin infections, and pododermatitis. 

Other adverse effects include (but are not limited to): urinary tract infections (even up to 11%), ear infections (up to 9%), vomiting, diarrhea, lethargy, anorexia, lipomas (benign tumors), polydipsia (excessive thirst), the swelling of lymph nodes, and aggression. 

4 — The Rebound Phenomenon (Withdrawal Issues)

Zoetis’ own studies showed that after 28 days on Apoquel, only 66% of dogs were considered a treatment success for their itching, and 49% were a treatment success for their dermatitis. This efficacy seems relatively low, especially compared to the risks associated with Apoquel’s use. Only two much smaller studies showed a higher efficacy, one with 72% (53 studied dogs) and the other with 82% (10 studied dogs). 

Some dog owners report that after a period of time on Apoquel, their dog’s allergy symptoms start to return. It’s not fully known why the symptoms come back despite being on the drug — perhaps the body builds up tolerance over time? Some veterinarians speculate it could be a sign of an underlying infection, possibly caused by the drug itself. The return of the allergy symptoms prompts the owners to either raise the dose (a risky decision) or quit Apoquel altogether. Since oclacitinib is not a steroid medication, the expectation is that you can safely take your dog off it overnight without worrying about any withdrawal symptoms … right? 

The accounts of many dog owners would say otherwise. What really happens when you want to take your dog off Apoquel? The first problem usually appears as soon as the twice-daily dose gets lowered to once daily, which is recommended by Zoetis after the first 14 days. The itching can rapidly increase and many vets will prescribe additional medication to mediate the dose transition. But when the dose is abruptly lowered to zero, the severe allergic symptoms can come back in as little as 24 hours!

A 2017 study confirmed this on a mice model. After Apoquel was rapidly discontinued, the researchers saw the itching episodes return with severe force! The study cites clinical reports of this happening to dogs, calling it “the rebound phenomenon.” After Apoquel is stopped abruptly, the body activates a high immune and inflammatory response, causing the itching to come back with a stronger force than before, resulting in intense itching episodes. It’s almost as if the immune system goes into full overdrive after being artificially suppressed for so long. 

If you are considering taking your dog off Apoquel, it’s best to taper slowly to give your dog’s (already altered) immune system time to adjust and to begin functioning normally again. Do this under the watchful eye of your holistic veterinarian! 

Final Thoughts on Long-Term Apoquel Use

Discussing the long-term use of Apoquel is like opening a can of worms. There are so many questionable and risk-filled aspects of this drug, not least because the manufacturer has a history of misrepresenting facts in order to sell the product. We have to be skeptical as dog owners and actively research any medicine prescribed to our dogs. Ironically enough, most of the information covered in this article is written on the package insert for Apoquel.

But how many dog owners see that insert? How many dog owners are able to give informed consent to this drug? How many veterinarians have warned their clients, carefully studied the package insert, or changed the frequency of prescribing Apoquel after seeing the adverse effects?

Some vets emphasize the importance of regular check-ups for dogs on Apoquel, stating that they should be screened for abnormalities (such as cancer) at least every six months. There’s no way of knowing how many dog owners could realistically afford that, let alone long-term. With everything we know about Apoquel, the risks are clearly immeasurably high, especially for cancer, which already kills one in two dogs. If you are looking for a safe, long-term allergy management plan for your beloved dog, Apoquel shouldn’t be your first choice. Check out these five alternatives to Apoquel instead!

Sources

Apoquel Prescribing Information. Zoetis, 12/2020. 

Cosgrove, B. Sallie. Wren, A. Jody. Cleaver, M. Dawn, 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.” Wiley, 21/11/2013. 

Gonzales, A. J. Bowman, J. W. Fici, G. J. et. al. “Oclacitinib (APOQUEL®) is a novel Janus kinase inhibitor with activity against cytokines involved in allergy.” Wiley, 05/02/2014. 

Marsella, Rosanna. Doerr, Katherine. Gonzales, Andrea, et. al. “Oclacitinib 10 years later: lessons learned and directions for the future.” AVMA, 25/03/2023. 

Lancellotti, A. Brittany. Angus, C. John. Edginton, D. Heather. Rosenkrantz, S. Wayne. “Age- and breed-matched retrospective cohort study of malignancies and benign skin masses in 660 dogs with allergic dermatitis treated long-term with versus without oclacitinib.” AVMA, 01/09/2021.  

“CVM Untitled Letters.” FDA, 05/01/2023. 

“Apoquel Untitled Letter.” FDA. 

Fukuyama, Tomoki. Ganchingco, Rachel Joy. Bäumer, Wolfgang. “Demonstration of rebound phenomenon following abrupt withdrawal of the JAK1 inhibitor oclacitinib.” 05/01/2017. 

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Luna’s passion for learning about canine psychology and behavior began when she adopted a severely reactive puppy from a local shelter. She is now a big advocate for positive reinforcement and compassionate training. As a writer, she strives to spotlight the topics that fly under the radar and be the voice for all who cannot speak for themselves.