Cytopoint Injection for Dogs – What You Need to Know

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If your dog suffers from itchy skin, red paws, and constant discomfort from atopic dermatitis or allergic dermatitis, you aren’t alone. Pruritus, which is the blanket term for this kind of itchy reaction, affects 30% of all dogs.

Given how common and insufferable it is, it's no wonder drug companies are constantly advertising the next miracle cure for pruritus. The most recent company to have made this claim is Zoetis, with their newest atopic dermatitis treatment, Cytopoint.

They claim this drug is different (in fact, they claim it isn’t even a drug!). But is Cytopoint really the miracle vets and the drug reps who educate them say it is? Or is it just another dangerous pruritus treatment that masks symptoms while throwing the body out of whack?

Keep reading to find out what our investigation revealed.

What Is Cytopoint?

Cytopoint (lokivetmab) is marketed as a “non-chemical” treatment for allergic dermatitis and atopic dermatitis. It is given in injection form once every four to eight weeks to treat seasonal and chronic pruritus.

It is true that this drug is not technically a chemical. Rather, it is a lab-made anti-canine interleukin-31 monoclonal antibody. In plain English, it is a protein made to act like certain cells in the immune system that neutralize pathogens. But in this case, the “pathogen” the drug neutralizes is interleukin-31, a specialized protein produced by the immune system.

Interleukin-31 (IL-31) is a type of cytokine that helps to activate white blood cells to target pathogens. In dogs with allergic and atopic dermatitis, the amount of IL-31 in the skin is elevated. Cytopoint works to reduce skin inflammation and itching by neutralizing this protein.

What Does IL-31 Do?

This article would be very short if all IL-31 did was cause itchy skin. But this protein is incredibly important to your dog’s immune system. 

Its main purpose is to alert immune cells to the presence of pathogens, such as viruses, fungi, and bacteria, in the skin, intestines, nervous system, and respiratory tract.

IL-31 also plays a vital role in balancing the cells responsible for making red blood cells. It also regulates the creation and destruction of connective tissues. Most importantly, it is necessary for activating a number of important pathways in the body, including those responsible for mediating cancer growth, inflammation, cell differentiation and growth, metabolism, and gene expression.

Cytopoint is marketed as not being a canine immune system suppression drug like Apoquel and other popular atopic dermatitis drugs. While it is true that it is not a blanket immunosuppressive, it does very much suppress a part of the immune system. And, given how many jobs this part has, suppressing it is very likely to cause system-wide problems.

What Happens When You Turn Off IL-31?

Many diseases are associated with the overproduction of IL-31, including dermatitis and irritable bowel syndrome. But neutralizing this protein entirely causes its own slew of issues. 

One paper discussing the potential benefits of IL-31 inhibitor use in humans warns that this protein needs to be better understood before drug options are explored because “there are still unclear points to be addressed when blocking the IL-31 pathway.” The paper goes on to hypothesize that IL-31 antigens and inhibiting drugs could cause upper respiratory tract infection, nasopharyngitis, peripheral edema, and elevated creatine kinase, among other concerns. This paper was published in February of 2023, seven years after Cytopoint was approved by the FDA.

Many veterinarians have hypothesized that IL-31 neutralizers like Cytopoint could cause symptoms similar to immune-mediated hemolytic anemia (IMHA). In this disease, the immune system mistakenly attacks red blood cells, causing fetal anemia. IL-31 is vital to the production of red blood cells, and antibodies like those in Cytopoint could quickly cause life-threatening anemia. 

Cytopoint Side Effects

Given how much IL-31 is responsible for in the body, you might expect Cytopoint to come with a long list of side effects. Somehow, though, Zoetis claims that this miracle drug has no side effects.

That’s right. According to the drug’s website, “A clinical study showed dogs receiving Cytopoint had no more side effects than dogs receiving placebo.”

How this is possible is covered at length here. It is also worth noting that the study in question was done on lab beagles with an unknown sample size.

Followup studies funded by Zoetis using pet dogs found vomiting, diarrhea, and lethargy to be commonly reported side effects in dogs being treated with Cytopoint. Painful injection site reaction, hyperexcitability, and urinary incontinence were less common but still reported. Most of these side effects, as well as facial swelling, seizure, anaphylaxis, and allergic reactions, ARE noted on the European Medicines Agency’s Cytopoint product information.

Interestingly, one research study conducted to look at the long-term safety and efficacy of Cytopoint failed to discuss side effects, adverse reactions, or any other points about the drug's safety. This was true despite the data clearly showing that 31% of the dogs suffered skin infections during treatment, with nearly 50% of those dogs suffering recurrent skin infections. Not surprisingly, this study was funded by Zoetis and authored by Zoetis employees. 

Another study looking at Cytopoint use in pet dogs reported that one treated dog was diagnosed with immune-mediated hemolytic anemia and immune-mediated thrombocytopenia. A second treated dog developed lymphoma during the study.

While Zoetis may not consider these cases to be representative of Cytopoint’s possible side effects, skin infection, anemia, and cancer are all theorized effects of IL-31 antibody use.

Side Effects Reported by Owners

If you think the non-reported side effects found in research trials are disheartening, brace yourself because the owner-reported ill effects of this drug are far worse.

On a single thread discussing Cytopoint safety concerns on Dog Forum, you’ll find dozens of owners whose dogs died shortly after receiving their first Cytopoint shot or during Cytopoint treatment.

One of the most disturbing of these stories describes a healthy 5-year-old pit bull who was put on Cytopoint to clear up his skin issues before undergoing ACL surgery. Within three days of receiving the injection, the dog began suffering breathing problems, extreme lethargy, and loss of appetite. Vets were able to stabilize him without a meaningful diagnosis, but his symptoms came back nine days later, accompanied by extreme anemia. The owner was forced to euthanize the dog 14 days after the initial injection.

Another tragically similar story tells of an 8-year-old rottweiler who developed itchy feet after CCL surgery. Four days after her vet gave her Cytopoint, she developed breathing problems, lethargy, and lost her appetite. After losing 22 pounds in three weeks and developing a limp in her non-surgical leg, the owners took her to the vet, demanding answers. Remarkably, they found a tumor in her non-surgical leg that did not show on scans from nine weeks prior. This tumor had somehow already metastasized and destroyed her lungs. 

Yet another tragic story tells of a 6-year-old Havanese who stopped eating three days after receiving the shot. At the vet five days post-shot, nothing remarkable was found, and she was treated with fluids. Hours later, the dog began screeching in pain while traveling in the car with her owner and then died instantly. The autopsy revealed she had a hole in her stomach and severe inflammation throughout the digestive tract, but no apparent blockage or foreign object was found.

With anecdotal stories like these, you always have to exercise a decent amount of caution. After all, coincidences do happen. But it is worth noting that every single symptom and cause of death in these three cases (as well as many more outlined on the forum) can be explained by the disruption of IL-31’s normal function. 

Cytopoint Is Not a Cure for Atopic Dermatitis

Whether you believe in the risks of Cytopoint for dogs or not, there is one even better reason not to use this product. And that is because Cytopoint, like Piriton, Apoquel, and so many other drugs, does absolutely nothing to address the cause of your dog’s pruritus.

Cytopoint might be effective at relieving your dog’s symptoms, but it does not address the actual problem causing the issue.

And atopic dermatitis has a lot of causes, many of which are signs of a larger systemic problem.

If allergies are the cause of your dog’s itchiness, then there are natural approaches you can take to reduce their exposure and ease their symptoms, including these highly effective allergy drug alternatives. If your dog suffers from hot spots, itchy paws, and/or ear infections, there are plenty of targeted natural remedies that can help with those without throwing the body out of whack or causing dangerous side effects.  

For allergic dermatitis, specifically, it is incredibly important to ensure your dog is flea-free. Fleas are one of the most common causes of itchy skin in dogs. But don’t use chemical products to get rid of them, as this will only cause more immune-compromising imbalances in the body. Instead, opt for effective natural flea treatments.

In almost all cases of atopic and allergic dermatitis, the cause lies in imbalances in the gut. Seventy percent of the immune system resides here in the form of beneficial bacteria, chemical signals, and symbiotic relationships between immune cells and probiotics. If your dog is producing too much cytokine protein in their skin, it’s likely because something is wrong in their gut.

Rebalancing the gut biome and healing the immune system requires feeding the right diet, avoiding medications that disrupt normal immune function (like Cytopoint) and harm beneficial bacteria, and providing healing probiotics and supplements. You can learn more about the gut–allergy connection and how to rebalance your dog's system naturally here.

How to Battle Atopic Dermatitis Naturally

If you want to help your dog find permanent relief from itchy skin, you have to address the cause. But if your dog needs some instant itch relief while you work to accomplish these larger tasks, there are some effective natural options out there.

Each of the remedies outlined below targets cytokine production to naturally reduce IL-31 in your dog’s system. Unlike harsh drugs and synthetic antibodies, these natural solutions work with your dog’s body to bring IL-31 production back into balance. This helps reduce the itch without putting your pup at risk for dangerous complications. 

Quercetin

Quercetin is a natural flavonoid found in many plants and foods, including apples, berries, green tea, and wine. It has long been used for natural allergy relief thanks to its ability to prevent histamine release. More recently, researchers have found that quercetin also helps to regulate the production of cytokines. 

There are many quercetin supplements on the market made specifically for dogs. Look for those that use whole food ingredients to ensure the best absorption rates.

Apigenin 

Apigenin is another flavonoid that helps to regulate cytokine production in the body. Uniquely, this flavonoid appears to target IL-31 specifically. Studies have shown that it is capable of greatly reducing inflammation and preventing the itchiness associated with atopic dermatitis.

Apigen can be found in supplement form for humans. It is not widely used in pets. However, it has been researched for use as a natural anti-cancer in dogs, and many naturopath vets prescribe it for dogs battling cancer. 

Natural sources of apigenin include parsley, celery, and cherries. If using the supplement form, speak to your naturopath vet about the right dose for your dog's needs.  

Don’t Settle for Dangerous Drugs that Mask Symptoms

It's true Cytopoint has a high success rate in reducing atopic dermatitis itch in dogs. But this success comes at a huge cost by depriving your dog's immune system of an important protein that helps fight infection, build red blood cells, fight cancer, and regulate system balance. 

But most importantly, Cytopoint, like so many other pruritus drugs, fails to address the cause of your dog’s itchy skin. 

If you want to help your dog find lasting relief from allergies and atopic dermatitis and live a long, happy life, you need to help them find balance. This is done through feeding a high-quality, biologically appropriate diet, reducing exposure to allergens and fleas, and using natural supplements that support cytokine balance and a healthy gut.

Sources

Gober, M., Amodie, D., Mellencamp, M. A., & Hillier, A. (2023). Long-term use of Cytopoint® in atopic dogs. Research Square (Research Square). 

Gober, M., Hillier, A., Vásquez-Hidalgo, M. A., Amodie, D., & Mellencamp, M. A. (2022). Use of cytopoint in the allergic dog. Frontiers in Veterinary Science, 9. 

Nchang, D., Cho, B. O., Shin, J. Y., Kang, H. J., Kim, J., Oh, H., Kim, Y., & Jang, S. I. (2019). Apigenin inhibits IL-31 cytokine in human mast cell and mouse skin tissues. Molecules, 24(7), 1290. 

Orfali, R. L., & Aoki, V. (2023). Blockage of the IL-31 pathway as a potential target therapy for atopic dermatitis. Pharmaceutics, 15(2), 577. 

Rosenkrantz, W. (2020). CANINE ATOPIC DERMATITIS — WHERE DO THE NEW TREATMENTS FIT IN? World Association for Veterinary Dermatology. Retrieved November 3, 2023.

Santana, F., Pinheiro, N., Mernak, M. I. B., Righetti, R. F., Martins, M. A., Lago, J. H. G., Lopes, F. D. T. Q. D. S., Tibério, I. F., & Prado, C. M. (2016). Evidences of Herbal Medicine-Derived Natural Products Effects in inflammatory lung diseases. Mediators of Inflammation, 2016, 1–14. 

Silva, G., Fachin, A. L., Beleboni, R. O., França, S. C., & Marins, M. (2013). In vitro action of flavonoids in the canine malignant histiocytic cell line DH82. Molecules, 18(12), 15448–15463. 

Zhang, Q., Putheti, P., Zhou, Q., Liu, Q., & Gao, W. (2008). Structures and biological functions of IL-31 and IL-31 receptors. Cytokine & Growth Factor Reviews, 19(5–6), 347–356.

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Sara Seitz worked in the pet industry for over a decade. In addition to being a certified dog trainer, Sara gained experience working as the general manager of a dog daycare and boarding facility, as the creator and manager of a pet sitting company, as a groomer, and as a dog behavior evaluator. She also has a bachelors in animal behavior from CSU. Currently, Sara works as a freelance writer specializing in blog, article and content writing.