Critical Analysis of Cytopoint in Veterinary Medicine and Specific Concerns for Dobermans
In the realm of veterinary medicine, Cytopoint, and Apoquel (read about Apoquel here) have emerged as prominent solutions for treating the symptoms of atopic dermatitis and other allergic conditions in dogs. Developed to manage itchiness and discomfort, these drugs have been praised for their efficacy. However, growing concern has evolved regarding their side effects, potential dangers, and legal controversies. This article aims to shed light on the issues regarding Cytopoint and caution that these drugs merely treat the symptoms but not the cause so that Doberman owners can make educated decisions on whether to treat their dogs with Cytopoint.
What is Cytopoint?
Cytopoint, also known as Lokivetmab, is produced by Zoetis. The medication is approved to treat clinical manifestations of atopic dermatitis in dogs. It is specifically designed to help reduce the itching and inflammation associated with this condition. Zoetis recommends that Cytopoint be administered subcutaneously once a month by a veterinarian. Hence, Lokivetmab is an injection. It is a biological therapy, technically a monoclonal antibody, specifically targeting and neutralizing canine interleukin-31 (IL-31), a key itch-inducing cytokine in dogs. However, it is essential to mention that IL-31 is a common player in allergic pruritus across species, including humans, and is not specific to dogs. Thus, while Cytopoint may be developed for dogs to account for differences from other species, the neutralization process of IL-31 to treat symptoms is not specific to dogs either. Crossover references regarding interleukin-31 (IL-31) from dogs to humans are abundant in the human and veterinary research literature.
While Cytopoint is said to target Interleukin-31 (IL-31) primarily for its role in causing itch in conditions like atopic dermatitis, it's important to note that this cytokine also plays roles in other bodily systems, including the lungs and intestines. There is evidence suggesting its involvement in the immune responses and inflammation in these areas. However, the effects of neutralizing IL-31 on these systems have not been thoroughly studied. Consequently, there is a lack of comprehensive understanding regarding the potential impacts of IL-31 neutralization on other organs and physiological processes. This gap in knowledge highlights a need for caution, as the short and long-term effects and systemic implications of IL-31 neutralization remain largely undefined. When considering treatments that target IL-31, such as monoclonal antibodies, it's essential to be aware of the current limitations in research and the potential for unforeseen effects beyond the intended therapeutic outcomes.
Side Effects and Dangers
While Zoetis, the manufacturer of Cytopoint, also known as Lokivetmab, generally considers the drug safe, significant adverse reactions exist.
List of adverse reactions as published by the European Medicines Agency (EMA):
Hypersensitivity reactions (anaphylaxis, facial oedema, urticaria) have been reported to occur in rare cases from spontaneous reports. In such cases appropriate treatment should be administered immediately.
Vomiting and/or diarrhoea have been reported to occur in rare cases from spontaneous reports and may occur in connection with hypersensitivity reactions. Treatment should be administered as needed.
Neurological signs (seizure, convulsion or ataxia) have been rarely observed in spontaneous reports
following use of the veterinary medicinal product.
Application site disorders (injection site pain, injection site swelling) have been reported very rarely
in spontaneous reports.
Clinical signs of immune-mediated diseases, such as haemolytic anaemia or thrombocytopenia,
have been reported very rarely in spontaneous reports.
The frequency of adverse reactions is defined using the following convention:
- very common (more than 1 in 10 animals treated displaying adverse reaction(s))
- common (more than 1 but less than 10 animals in 100 animals treated)
- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
- rare (more than 1 but less than 10 animals in 10,000 animals treated)
- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).
A Calculation:
Cytopoint states that 5 million injections had been given up until recently. Let’s do some math assuming that the 5 Million injections equal 5 Million dogs worldwide.
If 5 Million dogs received Cytopoint injections, and 9 dogs out of 10,000 experienced rare side effects, e.g., seizures, convulsions, ataxia, anaphylaxis, facial edema, urticaria, then 4500 dogs did experience one or more of these adverse reactions.
If 5 Million dogs received Cytopoint injections, and 1 dog out of 10,000 had very rare side effects, e.g., hemolytic anemia or thrombocytopenia, 500 dogs experienced one or more of these adverse reactions.
Please remember that no matter how small the number of adverse reaction cases may seem if your dog suffers a side effect, the percentage is 100% for them. Thus, it is of utmost importance that you weigh your benefits, risks, and try to treat the root cause rather than putting a bandaid on them by just treating the symptoms before giving a medication that can have rather serious side effects. While it is true that any medication has side effects, it matters what these side effects are and whether the risk of them occurring outweighs the benefit of the medication.
Long-Term Effects
Moreover, the long-term impacts on the immune system remain a concern for some veterinarians and pet owners. The reason is that Cytopoint has not been studied in the long term. As of the writing of this article, Cytopoint was only tested over a nine-month period at the longest. Given that many animals may be treated much longer with this medication since it does not eliminate the cause of the itching, no one can tell which immune system-modulating effects Cytopoint may have in the long run.
It is important to note that Zoetis themselves state in their leaflet that,
“…Avoidance or elimination of the allergen is an important consideration in the successful treatment of allergic dermatitis. When treating pruritus associated with allergic dermatitis with lokivetmab,investigate and treat any underlying causes (e.g. flea allergic dermatitis, contact dermatitis, food hypersensitivity); this product is not intended to be used as a long-term maintenance therapy if the offending allergen(s) can be successfully avoided or eliminated. Furthermore, in cases of allergic dermatitis and atopic dermatitis, it is recommended to investigate and treat complicating factors, such as bacterial, fungal or parasitic infections/infestations (e.g. flea and mange)…”
Unfortunately, in our years of involvement in Doberman communities around the world, we've noticed that Cytopoint is often prescribed without proper treatment of the underlying cause. Hence, many dogs receive monthly injections or injections every two or three months, depending on when the symptoms increase again over much longer periods than 9 months.
Effects on the Entire Immune System
Another concern is that no specific studies are readily available that directly investigate the effects of interfering with interleukin-31 (IL-31) on other parts of the immune system. Typically, research on cytokine blockers like IL-31 focuses on their role and efficacy in treating conditions they are implicated in, such as atopic dermatitis. However, understanding the full impact of blocking IL-31 on the broader immune system requires further study and is an essential area for ongoing research. Hence, it is crucial to recognize that, to our knowledge, no broader research exists at this time that investigated what potential negative effects on the immune system as a whole may arise when blocking a specific part of the immune system in dogs suffering from an underlying health condition that involves a possibly compromised immune system, to begin with. Any research available in this realm only included healthy laboratory dogs, which arguably may not represent a dog's immune system with compromised immune responses, such as those found in allergies. Moreover, at least one of these trials had a conflict of interest, as all people involved in the study had a connection to Zoetis, the manufacturer of Cytopoint. While it is not uncommon for pharmaceutical companies to initiate and sponsor research, it is nonetheless a conflict of interest when the study is run by people who (more or less) belong to the company as they hold a stake in the company or have received monetary compensation from them.
Legal Concerns
While specific lawsuits directly targeting Cytopoint are not extensively documented in the public domain, there have been instances where pet owners have raised legal questions related to the side effects and alleged misrepresentations of the drugs' safety. The veterinary pharmaceutical industry faces scrutiny over drug side effects similar to human medicine, and there is a call for transparency and comprehensive studies to understand the long-term implications of these treatments fully.
Why it Matters for Dobermans
Dobermans, like all dog breeds, have their own set of breed-specific health issues and genetic predispositions that could make the concerns surrounding Cytopoint particularly relevant. Here's why these issues might affect Dobermans especially:
Genetic Predisposition to Allergies
Dobermans are among the breeds that can be predisposed to atopic dermatitis, a chronic skin condition associated with allergies. This makes them more likely candidates for treatments like Cytopoint. However, their strong predisposition to allergic conditions means they might require long-term treatment, increasing their exposure to potential side effects of the medication.
Immune System Concerns
Cytopoint, an immunotherapy treatment for dogs with atopic dermatitis, could present concerns for Dobermans due to their predisposition to immune system issues, including autoimmune diseases. In breeds with inherent immune sensitivities, treatments affecting the immune response, like Cytopoint, warrant careful consideration and monitoring by veterinarians to avoid exacerbating existing conditions or triggering new immune-related problems. It's vital for Doberman owners to consult with their vets for tailored advice and monitoring plans when considering treatments like Cytopoint.
Skin Sensitivity
Dobermans have short coats and sensitive skin, which can exacerbate skin conditions and reactions. When treated with medications like Cytopoint, any adverse reactions or side effects, such as skin rashes or infections, could be more pronounced and uncomfortable due to their sensitive skin.
Cardiac Concerns
There is no specific evidence to suggest that Cytopoint directly causes cardiac issues in Dobermans. However, considering Dobermans are predisposed to certain heart conditions like dilated cardiomyopathy (DCM), any new medication should be administered with caution. It's essential for owners and veterinarians to monitor for adverse effects closely, especially since immune system interventions can sometimes have unforeseen impacts in breeds with specific genetic health concerns. Always discuss the risks and benefits with a vet before starting any new treatment for your pet.
High Metabolic Rate and Medication Sensitivity
Dobermans are large, active dogs with high metabolic rates, which can affect how they metabolize medications. This can lead to either increased susceptibility to side effects or a need for adjusted dosing, highlighting the importance of close veterinary supervision when administering medications like Cytopoint.
Beware and Find the Cause
While Cytopoint may offer valuable benefits for managing the symptoms of allergic conditions, it's crucial for Doberman owners to be particularly vigilant. Given their breed-specific health predispositions, Dobermans may face an increased risk of adverse effects from these treatments. Owners should engage in detailed discussions with their veterinarians and ask about finding and treating the causes rather than putting a bandaid on the symptoms. Doberman owners, in particular, should consider breed-specific health tendencies and closely monitor their pets for any side effects. Additionally, exploring alternative, less invasive treatments might provide safer options for managing allergies while accommodating the unique health profile of Dobermans. If it were our dog, we would only use Cytopoint as an absolute last resort if anything else has failed to treat the underlying cause. We would also insist on closely monitoring the dog with appropriate tests periodically while on the medication. We would avoid long-term use as best as possible by continuing to find and treat what causes the symptoms in the first place. Moreover, we would work with a holistic/integrative veterinarian and disagree with conventional veterinarians who would want to treat our dog longterm with Cytopoint.
Further Resources:
EPAR - Medicine overview:
https://www.ema.europa.eu/en/documents/product-information/cytopoint-epar-product-information_en.pdf
Interleukin 31 and targeted vaccination in a case series of six horses with chronic pruritus:
https://beva.onlinelibrary.wiley.com/doi/full/10.1111/eve.13408
Laboratory safety evaluation of lokivetmab, a canine anti-interleukin-31 monoclonal antibody, in dogs:
https://www.sciencedirect.com/science/article/pii/S0165242723000284
Establishment of an Intradermal Canine IL-31-Induced Pruritus Model to Evaluate Therapeutic Candidates in Atopic Dermatitis:
Disclaimer: The information provided in this article is for educational and informational purposes only and is not intended as a substitute for advice from your veterinarian or other healthcare professional. You should not use this information to diagnose or treat a health problem or disease or prescribe any medication or other treatment. Always consult with your veterinarian or other qualified healthcare provider before making any changes to your pet's healthcare regimen, especially if they have or suspect they may have a health problem. The author and publisher of this article are not responsible for any adverse effects or consequences resulting from the use of any suggestions, products, or procedures mentioned in this article. The use of this information is at the reader's discretion and risk.
