Scratching, licking, inflamed skin – if your dog is suffering from atopic dermatitis, you are battling these symptoms on a daily basis. Caused by allergies, there are several clinical treatment options available for this condition. Immunotherapy (allergy shots), antihistamines, and steroids are among those most commonly prescribed. Unfortunately, these options aren't ideal for many dog owners – sometimes, the side effects alone can be worse than the original symptoms.
Enter Cytopoint: a new type of medication on the market that is non-steroid and non-chemical. A natural antibody that is said to be without side effects. But instead of being an indisputable alternative to other medications, Cytopoint has found itself in hot waters, caught between the opinion of a pharmaceutical company and the first-hand experiences of its users.
Using Cytopoint for Dog Allergies
The core ingredient in Cytopoint is lokivetmab – an antibody that suppresses itching in dogs. Lokivetmab is a form of protein that binds to another protein called interleukin 31 (IL-31) and blocks it. It is precisely IL-31 that sends a signal for itching, and when lokivetmab blocks that signal, the itching goes away. With Cytopoint, this signal can only be blocked for three to four weeks before a new dose of the medication is needed. It is administered with an injection under the skin and requires a vet appointment.
The main question with Cytopoint is not whether it's effective in what it's trying to accomplish. Studies have shown that Cytopoint can reduce the itchiness in dogs by more than 50% within the first 28 days. The main question is, what are the side effects? Most drugs come with side effects, and one can hope the companies that manufacture them are as transparent as possible in disclosing them. This is where Cytopoint is different.
The package insert for Cytopoint only states: “Adverse events occurred at a similar frequency between treated and placebo groups in a study of 245 canine patients presented to veterinary hospitals and diagnosed with atopic dermatitis. […] Signs of patient discomfort on administration and adverse events occurred at a similar frequency between treatment groups.” If you read carefully, it's clear that adverse reactions were indeed observed in the clinical trial, but since they also occurred in the placebo group at a similar frequency, they apparently don't need to be disclosed.
Many dog owners who have tried Cytopoint felt blindsided by the side effects they didn't expect. The official information from the pharmaceutical company differs greatly from the users' experiences, and it's reasonable to ask how is that possible? Why were there reactions in the placebo group to begin with? There are several lenses through which we can examine the safety of Cytopoint, but let's start with the infamous clinical trial.
A Close Examination of the Clinical Trial
Cytopoint is manufactured by Zoetis, the world's leading producer of pet medication (including Apoquel, a tablet treatment for atopic dermatitis). A clinical study to determine the safety of Cytopoint was funded by Zoetis and carried out by its employees. 245 client-owned dogs with atopic dermatitis participated in the study, of which 162 were given lokivetmab, and 83 were given the placebo.
As already mentioned, there were no significant differences in terms of Cytopoint side effects between the two groups. This means that both groups showed similar, if not identical, side effects. These side effects are outer ear infection, dermatitis, bacterial skin infection, skin rash, vomiting, anorexia, lethargy, itchiness, diarrhea, hair loss, and fleas. The table below shows the frequency of adverse effects in both groups:
Aside from Cytopoint side effects mentioned above, four dogs in the trial had a severe adverse reaction. One developed immune-mediated hemolytic anemia and thrombocytopenia, another was diagnosed with diabetes, and two dogs with pre-existing conditions were diagnosed with lymphoma.
Why did the dogs react to the placebo in the first place? What was in the placebo? The only information we get from the study is that the placebo looked identical to the drug and had the same excipients. Excipients are actually a crucial part of the equation – they are substances without medicinal properties that act as a safe vehicle for the drug.
As one article states: “[…] in recent years excipients have proved to be anything but inert, not only possessing the ability to react with other ingredients in the formulation, but also to cause adverse and hypersensitivity reactions in patients. These range from a mild rash to a potentially life-threatening reaction.”
It's obvious that adverse reactions did occur in Cytopoint's clinical trial and at a high enough rate that they should have been noted and perhaps even followed up on with more research. Just because the side effects appeared in the placebo group doesn't mean they should get overlooked – if anything, this should have caused greater alarm! Excipients can make up to 90% of the medication, so we have to be aware of what they are and the side effects they can cause.
Excipients in Cytopoint
Excipients in Cytopoint (and presumably in the placebo) are histidine, histidine hydrochloride monohydrate, trehalose dihydrate, disodium edetate, methionine, polysorbate 80, and water for injections. Some of these can cause side effects similar to those observed in the Cytopoint clinical trial.
For example: at higher doses, histidine has shown side effects in impaired cognitive function, anorexia, vision impairment, weakness, nausea, drowsiness, and depression. Methionine can cause vomiting, drowsiness, and irritability. Caution is also advised for patients with liver disease. Polysorbate 80 has been connected with side effects of anaphylaxis, rashes, and hypersensitivity. It has also been linked to kidney and liver toxicity, specifically when used as a vehicle for another drug. Clearly, these substances do affect the system, and their effect should have been acknowledged in the original study's conclusions.
The Safety of Cytopoint in Veterinary Practice
In 2017, a round table report was published about the experience veterinarians had with Cytopoint in their clinical practice. Nineteen veterinarians participated who have given Cytopoint to hundreds of dogs. They have seen a significant improvement in a large percentage (60-70%) of their canine patients' atopic dermatitis after administering Cytopoint. Many of the dogs were itch-free from three to four weeks after the injection.
Several veterinarians have observed adverse reactions and have even noted that those have been very difficult to report to Zoetis, as the representative they spoke to doubted and minimized the reported effects. The most commonly reported side effects were vomiting, diarrhea, and lethargy. Other noted side effects were anorexia, pain on injection, hair loss, increased itch, rash, and swelling.
These side effects are in alignment with the European Medicines Agency's product information on Cytopoint. Classifying them as rare, they note the following reactions: anaphylaxis, facial swelling, rashes, vomiting, diarrhea, and neurological issues (seizures, ataxia). They also note injection site pain, injection site swelling, hemolytic anemia, and thrombocytopenia, classifying them as very rare.
Most veterinarians included in the round table have not seen their clients switch to Cytopoint as a sole treatment for their dog's atopic dermatitis. The possible side effects of long-term IL-31 suppression were also discussed, as IL-31 has been found in several essential places in the body, such as mast cells, spleen, bone marrow, ovary, and testes, to only name a few. No conclusions have been made, but there is a concern that blocking IL-31 for a prolonged time might negatively impact other immune functions in the body.
Dog Owners' Experiences With Cytopoint
We can look at trials and discussions on Cytopoint all day long, but the most potent information comes from people who have seen it work first-hand. If you search the internet for direct experiences dog owners had with this drug, you will find many. Among them, I found two threads that are regularly updated with the most recent encounters.
The first one is moderated and frequently commented on by a veterinarian. It also provides updates for some of the cases. The second one is a forum, so it's less organized and without a veterinarian weighing in, but you do have people's real-time reports of their experience with this medication. These are the stories that show us how Cytopoint works beyond the clinical environment.
Weighing the Pros and Cons of Cytopoint for Dogs
Any medication has benefits and risks. When making a decision that impacts the health of our beloved dogs, we have to weigh the pros and cons to determine whether the benefit of a certain treatment far outweighs the possible risks. With Cytopoint, the apparent benefit is the reduced scratching. However, for someone who has been watching their dog suffer the itchy agony for years, this pro alone may just as well outweigh all the possible cons. In this case, it's important to know about the side effects so they can be discussed with your veterinarian and properly prepared for.
In my view, the biggest con of Cytopoint is the lack of transparency surrounding the side effects. They are neither openly disclosed nor followed up on by more clinical research; they are left up to each individual dog owner to determine and deal with. This is a medication that only works from three to four weeks, so the question is, are dog owners prepared to put their dogs through possible adverse reactions every single month? Another pain point in this area is the pricing of Cytopoint. Roughly estimated, the cost per monthly appointment can be between $80 and $200, depending on the size of your dog. That is without the additional appointments to manage the side effects if they occur.
Finally, Cytopoint is a relatively new drug. It has only been approved in the US since December 2016 and in the EU since April 2017. The long-term effects of this medication simply aren't known yet, and there is a concern about how sustainable and safe it is when consistently used for months and years. It's important to note that Cytopoint attacks the symptoms, not the cause. It does not cure atopic dermatitis – it only suppresses its physical expression. There are a variety of alternatives to consider, and you can read about them in detail right here.
“Cytopoint®.” Zoetis Inc.
“Cytopoint.” European Medicines Agency, 15/09/2021.
“Cytopoint Product Information.” European Medicines Agency.
“Cytopoint: Experiences and Questions Roundtable.” American Academy of Veterinary Dermatology, 05/2017.
Michels, M. Gina. Walsh, F. Kelly. Kryda, A. Kristina. Mahabir, P. Sean. Walters, R. Rodney. Hoevers, D. Jacquelien. Martinon, M. Olivier. “A blinded, randomized, placebo-controlled trial of the safety of lokivetmab (ZTS-00103289), a caninized anti-canine IL-31 monoclonal antibody in client-owned dogs with atopic dermatitis.” Veterinary Dermatology, 19/09/2016.
Haywood, Alison. Glass, D. Beverly. “Pharmaceutical excipients – where do we begin?” Australian Prescriber, 01/08/2011.
Thalacker-Mercer, E. Anna. Gheller, E. Mary. “Benefits and Adverse Effects of Histidine Supplementation.” The Journal of Nutrition, 10/2020.
“Methionine.” PubChem, 18/09/2021.
Schwartzberg, S. Lee. Navari, M. Rudolph. “Safety of Polysorbate 80 in the Oncology Setting.” Advances in Therapy, 23/05/2018.
Elizabeth, Hannah. “How Much Does a Cytopoint Injection for Dogs Cost?” Bestie Paws, 31/08/2021.
Seitz, Sara. “5 Apoquel Alternatives That Are Better For Your Dog.” Ultimate Dog.