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Cytopoint vs Apoquel For Itchy Pups

Education > Dog Health & Behaviour 16th December 2020

Vanilla Pup spoke with Dr Amelia Ho from Mount Pleasant (Clementi) to understand more about Apoquel and Cytopoint for itchy dogs.

1. What is Cytopoint and how does it work?
Cytopoint is a monoclonal antibody, Lokivetmab that binds to IL-31, a pruritogenic cytokine, or simply put the “itch-sensation cytokine”. By binding IL-31 in the body thereby preventing it from binding to its receptor on nerves of the skin, Cytopoint rapidly reduces the transmission of itch (pruritus) linked to canine allergic dermatitis.

2. What is Apoquel and how does it work?
Apoquel is a newer drug on the market, it contains the active ingredient Oclacitinib. It is a selective Janus kinase (JAK) inhibitor, mainly acting against JAK1 and JAK3. JAK is a family of proteins that play a crucial role in the body’s signalling transduction pathways.

It has both antipruritic (anti-itch) and anti-inflammatory properties. As such, it decreases the production of IL-2, IL-4, IL-6, IL-13 and IL-31 (the itch-producing cytokine mentioned earlier).

3. What are the main differences between Cytopoint and Apoquel?
The main difference is the method of administration. Cytopoint is an, on average, once a month injection into the skin. Apoquel, on the other hand, requires daily oral dosing.

Additionally, Cytopoint was specifically created to target itch associated with atopic (environmental) allergies. However, it can be used for food allergies as well. It has been demonstrated to also assist dogs in other skin allergies where the specific cause of allergic dermatitis may be uncertain.

Apoquel, however, is labelled for pruritis (itch) associated with any allergic disorder, including flea allergy dermatitis, food allergies, as well as canine atopic dermatitis.

We describe atopic dermatitis in dogs as hypersensitivity or over-reaction to a range of common and otherwise harmless substances in the environment.

4. In what cases would you prescribe either or both? What factors do you consider?
Apoquel tends to be my preferred treatment for most dogs during an allergy workup period. It has a short half-life and as such, is out of an animal’s system within a few days. This way, we can assess quickly if our treatment trials have been helpful.

This is harder to achieve with cytopoint as it has effects that can last anywhere from 4 to 8 weeks and itch control cannot simply be started and stopped as you could with Apoquel. Apoquel is also a great use for dogs adverse to vet visits.

There are, however, scenarios where Cytopoint is a better first-line option. For example, when:

  • we can’t accurately dose Apoquel for dogs that are too small
  • the dog is younger than one year old
  • there’s difficulty pilling or owners have physical limitations that make administration of medications a struggle

I also commonly use Cytopoint to manage cases of adult-onset of demodicosis (infestation by the mite Demodex). In such cases, the pet’s immune system is unable to keep the mites under control so Cytopoint is able to provide good itch relief while allowing the immune system to work at full capacity.

I do use both concurrently during a flareup event where the dog has been triggered by an allergen and requires additional anti-itch relief. For example, if a dog on Cytopoint is doing well but lapsed on anti-flea control and subsequently presents pruritic (itch) for Flea Allergy Dermatitis, I use a short course of Apoquel to assist the animal in feeling more comfortable.

Other factors that I do consider are mainly the patient’s concurrent medications and medical conditions.

5. In your experience, which is more promising/effective?
Both drugs are much better alternatives compared to the use of older immunosuppressants, such as steroids and cyclosporin (Atopica). I would not consider one more promising or effective over another.

However, both Cytopoint and Apoquel may not be as effective in dealing with pruritus (itch) associated with severe pododermatitis (inflammation of the skin of the paw) or in ear infections. Steroids may sometimes still be required. Further studies pertaining to these are still ongoing.

Presently, I tend to prefer Apoquel because of:

  • the flexibility with dosing and
  • it being a more affordable option for many owners

Your veterinarian would be able to advise you on which may be a more suitable option for your dog.

6. What are the side effects of Cytopoint and Apoquel that you have observed in your patients?
Apoquel helps to decrease the itchiness and inflammation associated with the pet’s allergy flares without the side effects commonly observed in steroids, which include increased drinking, urination, eating, and panting. In general, we have found very few side effects with clinical cases.

Apoquel side effects
The most common reported side effect is mild gastrointestinal upset, which includes vomiting and diarrhoea. The reported incident rate in literature is around 2% and usually gets better with repeated administrations. Other side effects with low incidence rates that have been reported include a decrease in white blood cells, elevated liver enzymes, and new cutaneous masses.

Cytopoint side effects
For Cytopoint, it has been reported that lethargy can occur within the first 24-48 hours after injection. in rarer circumstances, there have been reactions to the excipient (inactive ingredient) used.

In severe skin infections, there is some speculation that the use of either drug may contribute to an imbalance of the skin’s natural inhabitants (dysbiosis). However, some clinicians have argued that allergy by itself is a disease of dysbiosis.

As a precautionary measure, because these are newer drugs on the market and we are still collecting data as we go, we get our patients on long term usage of Apoquel to come back for progress checks and routine bloodwork every 6-12 months, where possible. We typically look out for liver abnormalities and bone marrow suppression.

7. Are there any groups of patients that are not suitable for Cytopoint and/or Apoquel?
Apoquel is not registered for use in dogs below one year old or in cats. Because of how it modulates the immune system, it may potentially increase susceptibility to infection and infestation and exacerbate tumour growths. We should not use it in dogs with severe infections, demodicosis, or active malignant cancers.

In general, Cytopoint is safe to use in combinations with other medications including Apoquel, corticosteroids, NSAIDs, antibiotics, antifungals, and even with allergen specific immunotherapy.

8. Apoquel has been criticised for preventing JAKs from doing its job, suppressing the immune system and even causing cancer and other health conditions. What is your opinion on this?
This has been quite the hot topic in the field of veterinary dermatology. There is now over 5 years of experience with the drug and a review of its safety recently showed no unexpected findings.

On cancer
If we take a step back and analyse things on a whole, the first thing we need to acknowledge is that the rate of cancer in the general dog population regardless of Apoquel usage is exceptionally high. At least higher than it is in humans. The average number stands at around 400 cases per 100,000 dogs per year. So perhaps at some point of treating a patient for a long time, there is a high likelihood that at 10 years or older, there is an almost 50/50 chance it may get cancer regardless. And most often, it is probably unlinked to any administered medication.

Recent published literature has shown that occasionally, patients have developed benign or malignant cancers, but not any higher than the normal dog population would in the age range studied. The most common cancers noted were papillomas and histiocytomas, but we also have to bear in mind that Apoquel is used in young dogs, in which these benign tumours are fairly common.

Apoquel classification
I think a lot of the concerns arise from the classification of Apoquel as an immunosuppressive drug whilst other similar human drugs fall under JAK inhibitors. When Apoquel first gained approval, the only drug class that it could be categorised under was as an immunosuppressant.

Since then, several JAK inhibitors have been approved in human medicine and established as a class on their own. Label indication for Apoquel does warn that the drug may potentiate conditions, such as cancer and precautionary monitoring is advised. These are there as a result of Apoquel’s drug classification and not because specific studies have proven that its use has a direct effect on the development of cancer. In fact, there are works to reclassify the drug from an immunosuppressant to immunomodulatory as we speak.

The goal of Apoquel is immune modulation and downregulation of the mediators of itch and skin inflammation. JAK inhibitors are extremely valuable medications in human medicine. Numerous studies launched to investigate its use so far have not provided any evidence that the use of JAK inhibitors to treat various autoimmune or immune dysregulatory diseases could contribute to an increased risk for cancer.

With all this being said, of course, it is ultimately a fairly new drug on the market and adverse reactions are still being reported as we go.

9. Is it true that Cytopoint and Apoquel work for itch caused by environmental allergies but not itch caused by food intolerances?
Yes and no. As discussed above, Cytopoint was designed for canine atopic dermatitis. However, new indications have shown that it is equally effective in the treatment of dogs against other forms of allergic dermatitis. Apoquel, on the other hand, is registered for use in adverse food reactions and almost all forms of allergic dermatitis.

What we also need to understand is that the use of these drugs mainly serves to decrease the itching sensation observed in these allergic dogs. At the end of the day, we still need to identify and remove the trigger – the allergen. Without doing so, the body will continue to react and mount an itch response.

10. Do Cytopoint and Apoquel get less effective with time? If yes, what’s the reason?
There have previously been a few reported cases showing a decreased response with additional Cytopoint injections. Some dogs can start developing neutralising antibodies to Cytopoint, thereby making it less effective.

Recent study shows value in additional Cytopoint shots

However, a recent study conducted in the last year has shown that dogs can actually benefit from additional Cytopoint injections. Findings showed that around:

  • 65% of dogs achieved treatment success* after the first injection
  • 85% at the second, and
  • 93% at the third monthly injection

Editor’s note: The study defined treatment success as a minimum 20mm reduction in the client Pruritus Visual Analog Scale (PVAS) on the 30th day after the injection. PVAS consists of a sliding scale from 0 mm (normal dog) to 100 mm (extremely severe itch). For reference, 20 mm represents very mild or occasional itching, 40 mm mild/frequent itching, and 60 mm moderate/regular itching.

Short half-life of Apoquel means increased itch with reduced dosing

As for Apoquel, some dogs may experience an increase in the frequency of their itch when switched from twice-daily dosing to once daily. This is usually related to the short half-life of the drug (4 hours).

11. Why is it that some dogs respond better to Apoquel than Cytopoint and vice versa?
The exact reason has not been determined but experts in the field associate it to variances within the body’s signalling pathways and absorbance of the drug to achieve peak concentrations within the blood.

It is important to also bear in mind that attaining a 100% decrease in itch with these drugs is almost impossible. I like to say, if we are receiving an 80% improvement, then we are on the right track. Sometimes, we may need several medication trials.

We do know that if Cytopoint and Apoquel are going to be effective in an animal, you should be able to see its effects within the first 24-48 hours; although it may take a longer period to reach its maximum efficacy.

12. For some dogs, both Apoquel and Cytopoint don’t work on them. Why is this the case?
These drugs are extremely helpful to manage itch on a short and long term basis. But that does not mean flares cannot occur. In long-term allergies, dermatologists have stressed the importance of keeping infections under control. That’s because this often ends up being the reason why Apoquel or other medications might fail to work well.

Studies indicate that in dogs with atopic dermatitis, as many as two thirds will develop bacterial pyoderma and one third will develop Malassezia spp. dermatitis, also known as fungal dermatitis.