Dog Allergy

Cytopoint – the miracle cure for itching?

Cytopoint is considered a new miracle cure for itching in allergic dogs. But how does it actually work? How is it used? How high are the costs? And what side effects can occur?

In this article, we not only want to answer the above questions, but also explain why Cytopoint is causing such a stir in professional circles as well as among dog owners and what makes it so special. At the same time, we want to take a closer look at why you should perhaps dampen your enthusiasm a little bit!

What is Cytopoint?

Cytopoint (manufacturer: Zoetis) is a relatively new drug for the treatment of itching and skin inflammation in dogs with atopic dermatitis (ie an environmental allergy to pollen, house dust mites, mold spores, etc.). It has been available in Germany for a number of years – and is very different from all other medications used to treat itching in dogs (you can find more information about the other treatment options here ).

The active substance is not a small, chemically produced molecule (as with most other medicines), but an antibody – i.e. a large protein, as is constantly produced in many immune reactions in the dog’s body (e.g. in infections with bacteria or viruses). Cytopoint thus imitates a natural defense reaction, so to speak.

How does Cytopoint work?

The antibody in Cytopoint (Lokivetmab) is specifically directed against a certain messenger substance in the dog’s body: Interleukin-31 (IL-31). This neurotransmitter plays a major role in the sensation of itching .

IL-31 is produced in the event of an allergic inflammation and binds to nerve cells. These then send a signal to the brain: “Here’s something that itches”. The dog then scratches/licks/gnaws itself as a result. This often results in skin inflammation , which then intensifies the itching even further – a vicious circle of the typical allergy symptoms of itching and inflammation.

If a dog is treated with Cytopoint, the antibodies it contains combine with IL-31 and intercept the messenger substance before it can dock onto the nerve cells. This interrupts the itch signal and the dog stops scratching.

Think of it this way: The interleukin-31 (IL-31) molecules are nothing but soccer balls that are fired from the inflammatory cells in allergic dogs. Every time a soccer ball (i.e. IL-31) hits a goal (receptor on nerve cells), there is a reaction. Unfortunately, not just a goal celebration, but itching. The antibodies in Cytopoint are, so to speak, an army of goalkeepers: they intercept the balls so that no more goals are scored (or at least significantly fewer). And that ultimately results in less itching.

As already mentioned, the skin inflammation in allergic dogs is usually a result of constant scratching, nibbling and licking. If the itching goes away with Cytopoint, the vicious circle of itching and skin inflammation is broken and the dog feels better overall. He no longer scratches (or at least not as much) and the scabs, sores, redness, etc. heal.

More detailed explanation: What makes the antibodies in Cytopoint so special?

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What is special about Cytopoint is that it contains so -called caninized monoclonal antibodies . Admittedly, that sounds incredibly complicated at first. So let’s take a closer look. Most readers will probably remember the term antibody from biology class.

They are produced and released by certain immune cells, the plasma cells, in infections with bacteria or viruses, among other things. The antibodies have relatively specific binding sites with which they attach themselves to the so-called antigen (in the case of infections, these are bacteria or viruses) according to the key-lock principle.

This sets in motion an immune response that fights the infectious agents. In a “normal” immune response , many different plasma cells produce antibodies – and each plasma cell produces a different antibody that differs just a little bit from the others. As a result, the pathogen can not only be bound to one point, but there are many different points of attack (these different “points” on the pathogen are called epitopes). This type of antibody is called a polyclonal antibody .

The special feature of Lokivetmab is that it is a monoclonal antibody . This means that they are really identical “clones” of one and the same antibody – they all come from one plasma cell, so to speak, and all bind to the exact same epitope.

In contrast to polyclonal antibodies, this means that it is possible to precisely control what they bind to. So they have a very high specificity for their target, in the case of lokivetmab for IL-31 . The probability that they will undesirably bind to something else/wrong is therefore very low.

The successful development of such monoclonal antibodies was a milestone in both human and veterinary medicine. Namely, they allow you to attack or eliminate specific targets with much higher accuracy and with fewer side effects.

Areas of application (or research areas for the use of monoclonal antibodies) are now, for example, cancer, osteoarthritis, asthma and autoimmune diseases. Lokivetmab is the first and only approved monoclonal antibody in veterinary medicine .

Incidentally, caninized means that the antibodies in Cytopoint have been specially adapted to the body of dogs so that they are not perceived as foreign.

How long does Cytopoint work?

Here, too, Cytopoint differs from other anti-itch medications: it is a solution that is injected under the dog’s skin every 4-8 weeks . That’s how long the effects last (even longer for some dogs).

The itching improves in most dogs within 3 days – and in many dogs even about 8 hours after the injection.

So you don’t have to give the allergic dog tablets every day – but on the other hand you have to go to the vet every 1-2 months for the Cytopoint injection.

<h2″>What are the chances of success of the treatment?

There are not many studies that have examined this. An early publication states that Cytopoint halves the itching in the first month in about half of the treated dogs .

To my knowledge the largest study to date examined the effect on 135 allergic dogs. She reports at least a 50 percent improvement in itching in just over three quarters (77%) of the dogs after administration of Cytopoint. It also seemed to make no difference to the effect whether it was an environmental or feed allergy or a combination of these. The age and size of the dogs and the duration of the disease were also irrelevant for the success of the treatment.

According to the study mentioned above, Cytopoint seems to work just as well (or even a little better) than ciclosporin – a very effective drug that is also often used in allergic dogs.

The study (which – admittedly – was carried out by the manufacturer himself) also indicates that the itching could also decrease the longer Cytopoint is given: more than half of the dogs (approx. 55%) had itching after 3 months “normal” (“like a healthy dog”). After 9 months this was even the case for three quarters of all treated dogs (approx. 76%).

In another study , 21 allergic dogs were followed for a year . In about a quarter of the dogs, regular injections of Cytopoint alone prevented an acute flare-up for the entire period. All other dogs eventually developed allergy symptoms again (median after 63 days). The time it took to get there was twice as long as is typically the case with allergic dogs that do not receive any treatment – ​​but only half as long as with dogs whose skin is treated locally with cortisone twice a week instead. One-third of the dogs studied (33%) showed no flare-ups of allergy for at least 6 months.

Overall, however, there is still a lack of studies examining the effectiveness of Cytopoint over a longer period of time.

There are also dogs that do not respond to Cytopoint . IL-31 is probably not as involved in the itching in these dogs as it is in the majority of dogs. The manufacturer therefore recommends considering alternative treatment options if Cytopoint shows no effect after two injections.

What side effects are possible with Cytopoint?

At the moment everything indicates that Cytopoint is excellently tolerated by dogs – no serious side effects have been reported so far.

Some dog owners report that their dog (especially on the day of the injection) is a little weaker than usual and does not have as much appetite . In the studies conducted, some dogs also experienced pain at the injection site, vomiting and/or diarrhea (although it is questionable whether these symptoms were really related to Cytopoint).

Theoretically , however, some side effects are still conceivable, which, to my knowledge, have not yet been reported or could not really be associated with Cytopoint:

Anaphylactic reaction

Whenever a “foreign” protein (protein) is introduced into the body (especially with repeated administration), an anaphylactic reaction can theoretically occur. The possible symptoms range from wheal formation (wheals = localized swellings, look like mosquito bites) and vomiting to shortness of breath and shock . Such reactions would also be possible with Cytopoint (because the antibody it contains is a protein). Surprisingly, however, it seems that this has never happened before. This means that even if anaphylactic reactions can occur with Cytopoint, they must be very rare .

vasculitis

Unfortunately, it sometimes happens that antibodies and their “target structures” (antigens) aggregate in a very unfavorable way and form large immune complexes . These are “clumps” made up of many antibodies and antigens. These immune complexes can be washed away into the smallest blood vessels ( capillaries ) and clog them . This cuts off the blood flow in that area. In addition, the blood vessels become inflamed (so-called vasculitis).

This can have particularly serious consequences in the kidneys, for example, where renal insufficiency can occur. But skin symptoms with typically crusty, bleeding ear rims are also possible.

The antibodies in Cytopoint are actually structured in such a way that this shouldn’t happen – but nobody can rule it out at this point in time. To date, a few (two, to my knowledge) cases of vasculitis in dogs receiving Cytopoint have been reported worldwide. However, if you consider how many dogs have already been treated with it, it is questionable whether there is a connection with Cytopoint. However, even if this is the case, this side effect seems to be very rare .

What are the advantages of Cytopoint?

Cytopoint has some advantages over other medications used to treat itching in allergic dogs .

  • Cytopoint is much more targeted and precise than the other drugs. It specifically attacks only one messenger substance, while the “well-known” remedies are more likely to launch a kind of all-round attack on the immune system. So many immune responses that are useful are also inhibited in these. As a result, cortisone and the like often lead to an immune deficiency with susceptibility to infections – and tumor diseases also become more common with long-term administration (because the immune cells that fight tumor cells at an early stage are also weakened). Such a general immune deficiency is not to be expected with Cytopoint .

 

  • Cytopoint can be easily broken down in the body . Instead of breaking down the active ingredient in a complicated way, for example in the liver and excreting it through the kidneys (as is the case with many drugs), the antibodies are simply metabolized in the body’s cells to form naturally occurring products (such as amino acids). As a result, the burden on the liver and kidneys is minimal, so that Cytopoint is generally well tolerated by dogs with liver or kidney insufficiency. It can also be used to treat dogs with additional organ diseases.

 

  • Due to the targeted effect and the simple breakdown, the risk of side effects should be significantly lower than with other drugs. For example, cortisone preparations can cause undesirable effects in many different organ systems – and thus lead to diabetes mellitus (diabetes) or Cushing’s syndrome, among other things. Such side effects are not to be expected with Cytopoint.

 

  • Cytopoint also appears to be easily combinable with a number of other drugs . In studies, there were no undesirable side effects when administered together with other allergy agents such as Apoquel, cortisone preparations, Atopica, antihistamines or even desensitization. The combination with anti-parasitic agents, antibiotics, vaccinations and painkillers was also no problem.
  • So far, it appears that treatment with Cytopoint has had no effect on allergy test results . Unlike some other allergy medications, such as cortisone preparations, it does not appear to be necessary to stop taking Cytopoint before the test.

What are the disadvantages of Cytopoint?

Of course, no drug can only have advantages – there is always a catch in medicine. And so there are also a few points with Cytopoint that speak against the new “miracle drug”.

security concerns

Cytopoint has only been on the market for a few years . Even if very, very many dogs have already been treated with it during this time, there are still some safety concerns.

First, there is the possibility that IL-31 has other functions than “just” causing itching. Therefore, no one can predict the long-term consequences of turning off IL-31 with Cytopoint.

And secondly, as far as I know, there have not yet been too many studies on Cytopoint. That doesn’t have to mean anything now – but it is possible that over time further disadvantages will become known.

Effort and costs of Cytopoint in dogs

There are also some disadvantages from a practical point of view: If a dog is to be treated with Cytopoint, you have to take it to the vet every 4-8 weeks for the injection . However, this can also be seen as an advantage because it means that you don’t have to give him pills every day .

What is undoubtedly a disadvantage, however, is the quite impressive price . The cost of an injection depends on the size of the dog (large dogs receive more solution than their smaller counterparts) and range from around €80 to €160 (as of 2018) as far as I know. 

But here, too, it can be worthwhile: if the dog no longer needs any other, equally expensive medication and develops severe skin inflammation less frequently (for which you would then have to go to the vet again), the price can be put into perspective.

Loss of effectiveness possible

This is also a disadvantage of Cytopoint: unfortunately it sometimes happens that dogs no longer react so well to the injections . This is because they develop antibodies against the injected lokivetmab antibodies, so they can no longer work. This loss of effectiveness can be temporary, but it can also noticeably reduce the effectiveness of Cytopoint in the long term.

So is Cytopoint now the best remedy for atopic dermatitis?

No , you can’t quite say it like that.

The best treatment for dogs with atopic dermatitis is still desensitization (where the dog is exposed to the exact allergens it is allergic to, which slowly allows the immune system to adapt to them and no longer causes symptoms when exposed to them or they are at least weakened).

 Because desensitization is still the only way to treat the cause of atopic dermatitis– to grab the “evil” (the allergy) directly at the root. When desensitization takes effect, it is the closest thing to a cure: some dogs are symptom-free for years after stopping treatment. It also reduces the risk of a dog developing other new allergies.

In contrast, Cytopoint  is “only” a symptomatic treatment . This means that the itching and inflammation are treated, but not the underlying allergy. If you stop the Cytopoint treatment, the symptoms come back – it was just put a lid on them.

However, if desensitization is not an option – or if you are using desensitization but are still waiting for the treatment to take effect – Cytopoint is a good alternative and/or supplement to “standard” medication .

Everyone has to decide for themselves whether they prefer to

  • “well-tried” drugs, which can be associated with some (sometimes severe) side effects
  • or would prefer to choose a remedy that currently appears to be very well tolerated, but which has not been on the market for so long – so there is no long-term experience with it.

There is no right or wrong here . It is best to discuss with the veterinarian which treatment is most suitable for your dog!

Can Cytopoint actually also be used on cats?

No , unfortunately not. The antibody in Cytopoint is caninized, meaning it has been engineered to match the natural antibodies found in dogs. Cats would recognize the antibodies as foreign and fight them .

Also, as far as I know, the role of IL-31 in causing itching in cats is not known. It is therefore questionable whether an IL-31 antibody tailored specifically for cats would have any effect at all .

Conclusion

Overall, Cytopoint is an exciting new drug that we hope will deliver on what it currently promises! It offers a very good opportunity to treat dogs with atopic dermatitis symptomatically – even if they suffer from other diseases. However, it will still be a few years before we can say with certainty whether Cytopoint is as safe and well tolerated in the long term as it appears to be with short-term treatment.

 

References:

 

Michels, GM, Ramsey, DS, Walsh, KF et al .: “A blinded, randomized, placebo-controlled, dose determination trial of lokivetmab (ZTS-00103289), a caninized, anti-canine IL-31 monoclonal antibody in client owned dogs with atopic dermatitis.” Veterinary Dermatology, 2016; 27(6), 478-e129.

Michels, GM, Walsh, KF, Kryda, KA et al .: “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, 2016; 27(6), 505-e136.

Moyaert H, Van Brussel L, Borowski S et al .: “A blinded, randomized clinical trial evaluating the efficacy and safety of lokivetmab compared to ciclosporin in client-owned dogs with atopic dermatitis.” Veterinary Dermatology, 2017 ; 28(6), 593-e145.

Souza CP, Rosychuk RA et al .: “A retrospective analysis of the use of lokivetmab in the management of allergic pruritus in a referral population of 135 dogs in the western USA.” Veterinary Dermatology, 2018; 29(6), 489-e164.

Tamamoto-Mochizuki C, Paps JS, Olivry T Proactive maintenance therapy of canine atopic dermatitis with the anti-IL-31 lokivetmab. Can a monoclonal antibody blocking a single cytokine prevent allergy flares?” Veterinary Dermatology, 2019; 30, 98-e26.

 

https://www.zoetisus.com/

https://www.ema.europa.eu/

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