Cytopoint for IBD? Owner Comments
When I began this article on Zoetis' Cytopoint (lokivetmab) in 2015, Zoetis hadn’t gotten around to naming it - just called it CADI. The drug was approved by the USDA in 2016 (The FDA approves and monitors Apoquel because it is a "drug" - the USDA approves Cytopoint because it is a "biological" - but they have no effective monitoring system - in Europe, the EMA does both). At the time, it was unclear to a lot of us why Zoetis was planning to market two competitive drugs to treat the same condition. Over time, that became apparent. The Company realized that Apoquel, because of its broader action, had more potential to produce undesirable side effects. They hoped that Cytopoint which targeted only a single signaling compound for itch, IL-31 , would be more precise in its actions. You can read their most detailed (38 page) description of Cytopoint here.
Zoetis also saw Cytopoint as a good entry door into the precision drug market. That follows the same trend in human medicine: to use complex, bioengineered antibodies (ref) instead of small molecule drugs (like Apoquel) to treat complex diseases. Subsequently, they purchased the only competing company in that business, Nexvet. (ref)
Apoquel tablets bring dramatic relief to most dogs with skin allergies. The medication short circuits your pet’s “misinformed” immune system that has mistaken harmless things in the environment for things that might be dangerous if they invaded its body. It would be a superb drug – if it did only that. But it works at such a high level in the itch cascade (open the diagram at the top) that it can also interfere with a lot of important positive defenses that Nature designed your dog’s immune system to perform. When the inflammatory cascade is blocked at that high a level, your pet’s defenses against cancer, and infection are put at some risk as well. Now all medications have risks. Zoetis, the USDA, the EMA, many veterinarians and pet owners concluded that relief from the discomforts of canine atopy was worth taking those longer-term risks. Apoquel is a small molecule, so it can be absorbed when you give it orally. Cytopoint is a large molecule – too large to pass intact through your pet’s intestine. That is why it must be injected.
Apoquel blocks a whole family of messenger chemicals. They are called cytokines. Some of those messages encourage needless inflammation; but some of those same processes are essential elements of immunity and other body activities. (ref)
Cytopoint is a sophisticated monoclonal antibody (mAb) that targets and neutralizes a single itch-generating molecule, Interleukin 31 (IL-31), in your pet’s body. Many cells in your pet’s body have the capacity to produce IL-31. But most appears to be produced by a type of lymphocyte that originated in your pet’s thymus gland , and later disperse to guard entrances to your pet’s body, the T helper cells (aka Th2 cells, CD4+ T cells). (ref1, ref2, ref3)
As I previously mentioned, monoclonal antibodies are too large and complex to be absorbed intact when they are given by mouth to your dog while smaller molecules like Apoquel can be given orally to your pet and still be effective. The European directions say not to give Cytopoint to dogs weighing under 3kg (6.6lbs) (ref) ; the 2017 US inserts says to give 0.09ml/lb from a 10mg vial to dogs under 5 lbs (2.3kg). (ref)
Apoquel is not approved for dogs that are less than one year old. Cytopoint gives no age restrictions. Apoquel is not suggested for use in breeding dogs, or pregnant or lactating bitches and has not been tested in combination with corticosteroids, cyclosporine, or other immunosupressive drugs. Cytopoint does not give those restrictions. Directions just states that it has not been tested in pregnant, nursing or breeding animals.
I believe it is.
Folks who track your veterinary hospital visits say that one in six dogs that come through a veterinarian's door do so because they are itching. And of that group of clients, 15-20% leave with a diagnosis of atopic dermatitis or AD. So a lot of dog owners leave with pills or injections and they need to consider the safety and effectiveness of the medicines they agree to.
Prednisone is the ultimate shotgun medication for itchy dogs – and Atopica, not much of an advance. (ref) Both were frontline medications that veterinarians used to treat itchy dogs and cats before scientists gained a deeper understanding of the itch process. Prednisone, and, perhaps Atopica (cyclosporine), still have justifiable uses in treating itch (pruritus) in our pets today. That is because the newer, finer-tuned, alternatives are not effective in every dog. (ref) Corticosteroids like prednisone or Temaril-P® exert their influence in almost every cell in your dog’s body to one extent or another. (ref) They are fine for extinguishing or lessen short-term itching flare-ups; but I do not suggest them for long term or frequent use when they can be avoided. When used too frequently, they can produce the same signs as Cushing's disease , weaken joints and increase obesity. Prednisone is so powerful in its itch-relieving abilities that scientist still consider it the gold standard in itch relief to which all other itch relief products should be compared. (ref)
There are no one-size-fits-all solutions in life. I do not believe that dog owners who feel their dog is better off relieved from the misery of chronic dermatitis with corticosteroids like prednisone or immunosuppressants like Atopica should be criticized. No one knows your dog and your circumstances better than you do and for some, the quality of their pet’s life today overrides worries about the future. For others, the cost of these fancy medications is just too great. But as a veterinarian, I feel its my job to make you aware of what might or might not occur farther down the road so that you can make decisions that best fit your situation.
I hope that Cytopoint will be more precise in what it does in your pet's body than corticosteroids, Atopica or even Apoquel. It was designed to go after just one messenger molecule involved in itch, IL-31, - not a whole class of messenger molecules like Apoquel, prednisone or Atopica do. Cytopoint is veterinary medicine’s first venture into a group of medications never before used. So there is no doubt in my mind that veterinarians, dog owners, the USDA and the pharmaceutical companies themselves are still quite early into the learning experience.
To date, we only have a couple of Zoetis-funded studies of a few healthy young beagles that were followed for relatively short periods of time. (ref) Zoetis references “data on file” in a lot of their Cytopoint brochures that discuss the safety and effectiveness of Cytopoint. But they were not willing to let me peek at that data when I asked them. Once a drug gains governmental approval, there is no incentive for drug companies like Zoetis to continue formal research on their products. After approval, its strictly feedback from pet owners like you that modifies opinions, helps motivate the USDA to look out for your pet's interests and drives change.
I believe that Cytopoint should be safer than Apoquel. I am not alone. Veterinary school students have a soft heart and a penchant for adopting health-issue dogs. Reading their online chatter blogs, its apparent to me that most of the veterinary students with atopic pets and the dermatology professors they interact with believe that Cytopoint is a safer drug than Apoquel.
Safety aside, Cytopoint is approved for dogs less than one year of age and Apoquel is not. Unlike Apoquel, Cytopoint has not been associated with liver changes. Cytopoint is probably less likely to negatively affect pets with multiple health issues. Things like increased susceptibility to infections, concurrent tumors, blood abnormalities or the many medications used to treat them.
There are some other factors to consider: Some dogs accept tablets more readily than injections and vice versa. In some dogs, skin allergies are seasonal, so Apoquel side effects are less of an issue. Canine atopy (= skin allergy= AD) is a highly complex process with many alternative routs that lead to the same urge to scratch. So one drug or the other could have quite different effects in one dog versus another.
Some believe that dogs receiving Cytopoint need less frequent or less extensive laboratory monitoring than those receiving Apoquel or other drugs. In 2017, Cytopoint is really too new on the market to conclusively say that. It is also already apparent that there is high dog-to-dog variability in the effectiveness of Cytopoint.
Because Cytopoint was tailor-made to be accepted by only a dog’s immune system, you cannot give it to your cat. Although Apoquel is not approved for cats; it has been given to cats experimentally. (ref)
No one completely understands. In some of their distributed material, Zoetis suggests that Cytopoint decreases the skin inflammation that causes itching. (ref) In others, they suggest that it primarily blocks nerve transmission of itch signals from the pet's skin to its brain. In some, that they both occur. That is because both Cytopoint and Apoquel came onto the market long before scientists fully understood the complex signaling systems that they affect.
What we do know is that in mice that were bred to suffer from something similar to atopic skin disease, drugs similar to Cytopoint seems to tie up the IL-31 messenger before it can tell nerves ending in the skin and others in the spinal cord to transmit itch signals to the brain. According to some, those IL-31 messenger molecules might even increase the number of those itch-sensitive nerves in the skin. In those mouse models, drugs like Cytopoint have little if any effect on skin inflammation itself. These mice were bred to have too much (“overexpress”) IL-31. We do not know if some, or all dogs with skin allergies genetically overexpress as well. (ref1, ref2, ref3, ref4) In the only study that I know of, the blood of over 40% of 223 atopic dogs did not show elevated IL-31 levels (and thus might not be helped by Cytopoint). Zoetis/Pfizer could not explain that. They theorized that in 40% of the dogs, IL-31 was not a major factor in the pet’s itching or that IL-31 might be present in their skin but not their blood stream. They did not pursue if it was the low or high IL-31 dogs that were the ones most helped by Cytopoint. (ref)
At this point in time, I believe that Cytopoint’s acts primarily by blocking nerve sensations. In most dogs when it works, it acts too fast for it to be working on the actual inflamed skin. That does not mean that your pet’s skin isn’t going to get any better when on Cytopoint. Ninety percent of the damage you see in an itchy dog’s skin is caused by the scratching itself and with that gone or reduced, the dog’s skin is going to heal – just as it would wearing an Elizabethan collar. There are others who disagree as to where IL-31 has its effects and they have their evidence as well. (ref)
In many cases, probably not. But it is most certainly worth a first try for your pet.
mAbs like Cytopoint and inflammation inhibitors like Apoquel are going to give a lot of relief to some dogs, moderate relief to some dogs and little to others. You or your veterinarian won’t know which is most effective for your dog until you try them. I would begin with Cytopoint because, the current opinion is that it is safer. The feedback I often get from dog owners who have used both is that the anti-itch effects of Apoquel were more dramatic than Cytopoint – but I would first see if Cytopoint injections alone or along with topicals were sufficient to reduce your pets itching to acceptable levels (I did not saying itch-free - I said acceptable levels). The same goes for Apoquel. Some dogs are given the double, 2-dose- per-day suggested for the first 14 days indefinitely. Perhaps unrealistic improvement was what they demanded. Perhaps they could not or would not use the topicals that give added relief. Clients tell me that those stubborn Apoquel-resistant cases are also the ones least likely to get a full 4 weeks relief from Cytopoint. But most tell me that they are still happy they made the switch because skin tumors shrunk or disappeared and abnormal blood work results improved.
An underlying problem for dog owners, and veterinarians alike is that we tend to treat AD (allergic skin disease) as if it was one disease. It is not; it is many diseases. All these dogs itch, their skin gets red, they smell, their hair falls out. But the system is extremely complex and can go wrong at many locations and in many ways. In some dogs, the problems might be an immune system prone to make errors, in others genetics that favor defects in the pet’s skin barrier. (ref) So one treatment is not going to cure all dogs. That’s why desensitization (allergy shots) might be worthwhile for a few dogs (ref), diet modification for a few, immune suppression for some and topical medications for others. Veterinarians have very little in the way of tests that will predict which dogs will do best on which treatment(s).
As you can see from my diagram at the top of this page, your pet's itch is the end result of a highly complex process (cascade) in which a great number of chemical players and cells take part and communicate with each other (= "crosstalk") :(antigens,T-cells, antibodies, messenger chemicals, receptor stations [=docking stations], skin barrier defects, sensory nerves that lead to the brain). It has fail-safe avenues (pathways), so if one road to itching is blocked, another one can sometimes take its place (a very plastic system). If you want to delve deeper than my short explanation, an article focused on allergic skin disease in humans describes all that well. (ref)
No one has studies why some dogs itch and others do not. But we do know from humans and mice that the amount of IL-31 can go up as we age. (ref) We know that some humans and mice are just prone to produce too much ("overexpress") IL-31 even without allergies and that some humans itch because they produce antibodies against their own normal tissues (autoantibodies). (ref1,ref2)
Ear infections and paw licking are the hardest symptoms of dog allergies (AD) to cure since they often have other drivers in addition to allergy. Your dog's personality has a large effect on paw licking and grooming behavior – particularly in the cupcake breeds. Floppy eared or compressed faced dogs have most of their ear problems due to conformation and skin composition. Scooting can be related to perineal (rear end) or vaginal itching, but also to dietary-driven anal gland impaction and bowl issues like IBD that Is not going to respond to Apoquel or Cytopoint. And at some point, the anal gland’s ability to normally contract and empty is compromised to a point where it will never again be normal. In that situation, I generally remove them.
About 80% show improvement in the first 24 hours. The rest that are going to show improvement usually do so by the end of the second day. There are a few exceptional cases where it might take up to three days. It will take considerably longer for your dog's skin damage to heal and its hair to grow back. If your dog is already on Apoquel, a gradual decrease in Apoquel as it transitions to Cytopoint is probably going to give your pet a smoother transition.
The EMA says that Cytopoint starts working within 8 hours and I have known some cases where relieve began even faster. (rptref) But there doesn’t seem to be much relationship between how rapid relieve begins and how long that relief will last.
Some pet owners might have already had experience with periodic injections given by a veterinary dermatologist to desensitize their dog. That vet might have indicated that with time, your dog might require fewer or no additional injections. That is not the case with Cytopoint – if it "cured" a dog, we would have to rethink what we think we know about the drug and the itch process. Monoclonal antibody therapies rarely get more effective with time. Usually they are either effective by the third injection or they remain ineffective. Of course, when allergies are seasonal, a drug like Cytopoint might appear more effective or less effective depending on the time of the year.
Zoetis advertises 4-8 weeks of relief from a single injection. But 3-5 weeks - with the average being about 3.5 – 4 weeks before dogs begin to lick their paws again - is more realistic. My feedback indicates that very few dogs remain under itch control for as long as 8 weeks. But I do occasionally get emails about those 8-week miracles.
Zoetis also conducted unpublished studies that showed that the half-life of a Cytopoint injection in the body was approximately 9 days – not a month. (ref) The same report suggested that the amount of the drug remaining in the body might build up over time with repeated monthly injections and increase the anti-itch effects. No evidence of that was given. One can still dream of 8-week protection. The Cytopoint minimum monthly dose is 2mg/kg. There is a human anti-IL-31 drug in development for itching called nemolizumab. In one study, it appeared to suppress itching in 5 out of 6 monkeys for almost 2 months when given at half the Cytopoint dose. (ref)
There are cases where Cytopoint started off quite effective after the first shot or two but then slowly lost its effectiveness during later injections. That sort of effect has been seen with other biological medications. It is often associated with the patient developing antibodies (anti-drug antibodies or ADAs) that attack and neutralize drugs like Cytopoint. The EMA report I mentioned earlier said that Zoetis detected none of those ADA antibodies in 18 beagle dogs given Cytopoint injections over a 30-day period. (rptref) The EMA then requested a field study. One hundred and forty-two client-owned dogs with AD were given Cytopoint injections monthly for 3 month. Three developed ADAs. Post-injection hives are sometimes associated with the development of ADAs; although sensitivities to other constituents in the Cytopoint bottle and pre-existing autoimmune issues have the potential to cause hives too.
Zoetis reported no health changes in beagles given 1, 3 or 9 mg/kg three times during 1 month (2 mg/kg is the minimum suggested Cytopoint dose). Later, they repeated the experiment and gave six more beagles 1 or 9mg/kg once a month for 7 months and saw no side effects (rptref)
Although the current package insert says, “give every 4-8 weeks as needed”, many vets
give it more frequently in dogs that cannot make it the full 4 weeks. I do not know of any dogs that were given Cytopoint more frequently than every 3.5-4 weeks that developed problems that were thought to be associated with giving the shots closer together than suggested on the label. But check now and then with my comments page to see what comes in.
IL-31 is an important player in at least some cases of itching. Every furry or feathered animal on this planet itches (A "genetically conserved” behavior). So there must be some good reasons for it. Itching - when it is not misdirected - is self-protective (as are other skin sensations such as touch, pain, vibration, cold and heat). At the level of your dog’s brain (higher up the line than where Apoquel or Cytopoint work), it is due, at least in part, to the release of a nerve signal transmitter (neurotransmitter NPPB). (Yes, the same or similar compound damaged hearts release link BNP). (ref) NPPB also acts as an antimicrobial peptide (it kills bacteria and fungi). NPPB’s other biological actions include, widening of skin blood vessels (vasorelaxation) and decreasing renin and aldosterone levels which also increase the blood supply to your dog's skin. Protective antibodies and germ-fighting cells arrive at your dog's skin via its blood stream. So in times of troubled skin, a large blood supply is helpful. But if your dog’s skin were always highly vascular (lots of blood and blood vessels), its skin would be much less durable, it would bleed too much from minor injuries, too much body heat would be lost and bacteria and parasites would find cuts and nicks a much easier entry into its body. Scratching, when not misdirected, also helps in removing irritating surface contaminants and dispersing or killing, flies, mosquitoes, lice etc. (ref1, ref2)
We know little about what IL-31’s normal roles in your dog's body are. But its a cornerstone of medicine that messenger chemicals in the IL-31 family are used in different parts of the body for different purposes. We know that some of IL-31’s functions change, depending on the animals’ stage of development and age too. We also know that IL-31 docking stations (the receptors for IL-31, ie IL-31RA) exist in many tissues throughout your dog’s body. What roles stimulating those docking stations with IL-31 play and what the consequences of interrupting those message pathways with Cytopoint will be we do not know. We know that a lot of sensory nerves are receptive to IL-31. We know that along with nerves, the basic cells of your dog’s skin (keratinocytes) receive IL-31 messages as well. So does the lining of your pet’s lungs and muscle cells. (ref) We know that eosinophils, white blood cell involved in allergies, and other cells involved in body defenses receive IL-31 messages too. (ref) Low levels of IL-31 also naturally occur in your dog’s thymus gland, testis, spleen, and kidneys. (ref) We do not know what its functions are in those locations. When a drug like Cytopoint cancels IL-31 messages, cells with the IL-31 receptor are going to act somewhat differently. But neither I nor Zoetis can tell you how. On a comforting note, I can tell you that mice that have been bred to lack all of their IL-31 mailboxes appear - at first glance - to be normal. But I can't seem to find anyone who has kept them longer than they needed to to complete their experiments or paid much attention to their general health and behavior. (ref1, ref2) After all, they're just lowly mice. (ref)
On another positive note, Cytopoint might even be helpful to dogs with inflammatory bowel disease - since IL-31 stimulation is thought to play a role in chronic intestinal inflammation as well. (ref) (let me know if you find this to be the case in your pet)
As if that were not complicated enough, I am embarrassed to tell you that the IL-31 mailboxes (IL-31Rα receptors) receive and are activated by a second type of message (you see, the IL-31 receptor is a dimer - a dual function receptor). The mailbox also accepts messages from another signaling compound called oncostatin M (OSM). , whose normal functions are just as poorly understood and complex as IL-31. (ref) We also know that the effects of OSM appear to intensify when IL-31 is blocked or removed. (ref) Cytopoint is not known to directly affect OSM; but its presence at normal levels is critical to good health. (ref) We also know that many messenger chemicals in the IL-6 family where IL-31 belongs have redundant (overlapping) positive duties in the body. (ref1, ref2)
Most dogs have no immediate side effects to Cytopoint injections. It has not been on the market long enough to judge its long-term effects.
Although rare, I suppose post-injection mopeness (lethargy), eye irritations and hives are the most common side effects I know of. But quite a few dogs just aren’t themselves for a day or two after a visit to an animal hospital for any reason - its just not one of their favorite destinations (They thought you were just taking them out for a drive and then, BINGO !). Most of the other reported side effects of Cytopoint are minor. They include occasional post-injection vomiting and diarrhea (that could also be psychosomatic).
Even rarer are severe reactions that affect breathing. The kind one occasionally sees after pet vaccinations. (ref) When they occur, it is most commonly in the bulldog breeds that have trouble obtaining enough air on their best days. It is also very difficult to decide if such an attack was due to the agitation of being brought to an animal hospital, that of the restraint necessary to inject the dog, or due to overheating that might have occurred in the process.
I attribute hot spots and other skin appearance problems that occur after a Cytopoint injection to be more likely due to incomplete relief than to some side effect of the drug.
Although Cytopoint instructions suggest that the complete dose be given in one location; some bigger dogs flinch less and show less signs of injection discomfort or pain when the dose is divided and given at two locations (letting the refrigerated vial warm to room temp before injection also helps).
As I mentioned earlier, some things that flare up in atopic dogs can be mistaken for side effects of a Cytopoint injection. Ear infections and paw licking are the hardest facets (symptoms) of AD to cure because they have other drivers (causes) in addition to your pet’s allergies. Your individual pet’s personality has a big effect on paw licking and grooming behavior – particularly in the cupcake breeds. Floppy eared and compressed-faced dogs have most of their ear problems due to skin folds and skin composition. Scooting and rear end licking can be related to perineal or vaginal allergic itching, but also to UTIs, dietary-driven factors (inappropriate diet and treats) that lead to anal gland impaction (ref) or to intestinal issues like IBD (ref) and of course, the old bugaboo - fleas. None of those things are likely to respond to Cytopoint or Apoquel.
Some folks report that their dogs gain weight on Cytopoint. Perhaps they just feel better and are more inclined to a hearty appetite. Perhaps there is more to it than that. (ref) But most owners report that their dog's weight didn’t change.
If your dog experienced confirmed staph-related skin problems in the past - when it was not receiving Cytopoint or Apoquel - then the likelihood of those drugs playing any part in a current staph relapse is remote.
But several dog owners whose dogs had never had that problem before have told me that their pet’s itching problem improved considerably on Cytopoint - but the pet went on to develop staph skin infections or hot spots. That might not be a failure of Cytopoint to do what it was intended to do. It might be that it is doing its job too well.
From shortly after their birth and for the rest of their lives, staphylococcus bacteria are part of all dog’s normal resident skin flora. (ref) The normal place for these bacteria to reside is on and between the two or three top layers of the cells that make up your pet’s skin. You can see them in the diagram above. Those outer skin cells (keratinocytes) are dead. As the living, deeper keratinocyte cells mature, they migrate up from the deeper (basal) layers until they become the skin’s protective surface barrier. Expand the diagram above to see that in detail. Their migration is partially under the control of IL-31 – the messenger chemical that Cytopoint is designed to neutralize. IL-31 affects keratinocyte development (differentiation) in multiple ways. At high levels (when "overexpressed") the skin thins and itching can occur. But at low doses, IL-31 promotes a healthy antimicrobial barrier and normal migration of the deep keratinocytes to the surface. IL-31 also stimulated keratinocytes to produce antibacterial compounds (antimicrobial peptides) which help keep the number of staph on your dog’s skin under control. (ref1, ref2) When the protective effects of those antibacterial compounds are lost, the upper layers of the skin can be penetrated (breached) and bacteria can invade the deeper living layers of your pet’s skin. So, in at least some dogs, complete neutralization of IL-31 might not be a good thing.
So from time to time - skin infections in pets taking Cytopoint might need some assistance in getting staphylococcus and similar skin bacteria back under control. When your pet’s lymph nodes are not already involved (enlarged), its blood counts are normal, and it is not showing other signs that the bacteria have invaded deeper parts of its body, I suggest you try topical antibacterial shampoos and lotions before you resort to antibiotics such as Convenia® or other cephalosporins. It is true that those and other antibiotics are usually a convenient quick fix - the first or second time they are used. But with repeated use and time, staphylococci are experts at becoming resistant to all antibiotics (become MRSAs). (ref1, ref2) Its not a good idea for you or your pet to encourage these resistant bacteria to loiter around your home. (ref)
So why not first try medicated shampoos to see if they won't get the problem under control ? Remember, antibiotics are a scorch-earth option - they destroy the good bacteria on the inside and outside of your pet as well as the bad ones and probiotics aren't going to bring all the good ones back. (ref) My preference is for canine skin care products that contain benzoyl peroxide, chlorhexidine or povone iodine as their active ingredients. (ref1, ref2, ref3)
There are veterinary dermatologists who recommend rinsing dogs in a 0.005% solution of household bleach to kill staph. (ref) I use a lot of Clorox in my practice to disinfect utensils and cages. But it has been so hard on my hands over the years that I have never brought myself to use it on animals. When used on animals, I would think that in the presence of skin proteins, it would produce irritating trihalomethanes.
Scrubs and lotions that contain hexachlorophene are great at reducing staph skin counts. But they are too harsh on the skin of dogs for application to large areas – particularly when those areas are inflamed. Wipes containing nisin are also available. I have no experience using them. Shampoos are most effective when massaged well and left on the dog for at least 10 minutes before being washed off. Avoid getting them in your pet’s eyes.
After these shampoos have thoroughly dried, some dogs benefit from an emollient lotion designed to enhance filaggrin function. Filaggrin forms a part of your pet’s skin barrier against staph. It promotes normal skin acidity (pH), moisture retention and resistance to staph penetration. Some of these products contain high linoleic/oleic sunflower seed oil, others mineral oil, glycerin, propylene glycol and various carrier oils. Avoid any that have lauryl sulfate or fragrances as ingredients.
Some veterinarians suggest staph lysate injections to help deal with staphylococcal skin infections. I have little faith in that product. That is because it is basically a vaccination against staph - and those anti-staph vaccines have never worked in humans. (ref) It is an effective skin barrier, rather than antibodies, that keeps staph in check. (ref) There are still folks hoping to develop effective anti-staphylococcus vaccines - but this is 2017 and that's in the future. (ref)
(How do you handle staph flare-ups in your pet ?)
Once your dog has received two or three monthly Cytopoint injections, the likelihood that it will improve in effectiveness later is not high. If your dog is fortunate, relief will remain about the same. Other medications and treatments that you add to the pet's treatment plan may take up the slack; but by the current concept we have of how Cytopoint works, its effectiveness should not increase over time. I did mentioned earlier that there is often a rebound effect when dogs stop taking Apoquel. So you need to give Cytopoint at least a 3-months window of opportunity.
Pet owner reports for both Apoquel and Cytopoint show dramatic improvement in some pets, but only moderate or minimal improvement in others. One might try to get around that by increasing the dose or frequency that each drug is given. In the case of Apoquel, that can also increase the likelihood of side effects. In the case of Cytopoint we just don't know. I would be inclined to consider spacing Cytopoint injections closer together if for the first 2-3 weeks after its monthly injection results were satisfactory, but the last two weeks of the month the itch returned. I would do that before I fell back on supplemental Apoquel. (If you and your pet face that issue, I want your feedback on that as well).
Cytopoint is a monoclonal antibody - and mAbs are big. The bigger a protein-containing molecule is, and the more that is given, the greater the chances are of the pet’s immune system taking note of it and decide to destroy it. () That can explain why mAb drugs sometimes become less effective over time. In one Zoetis study, they did not report these anti-Cytopoint (ref) antibodies (ADAs) ever forming (ref) but in others, they did. (ref1, ref2)
For the human anti-itch mAb drug, dupilumab, about 7% of patients develop these type of anti-antibodies (antibodies the body produced to neutralize an injected therapeutic antibody drug). Interestingly, about the same number of patients that never received that drug were also found to have those antibody. So there must be some sort of cross-over, multifunctional antibody circulating around in these patient's bodies. (ref) Those sort of things (promiscuous antibodies) and cross-reactivity do happen in people and livestock - a case of mistaken identity - (ref1, ref2, ref3) ; perhaps similar things occur in dogs. For other human mAb medications, the number of patients that develop anti-antibodies against them is considerably higher. (ref)
Dogs are so genetically diverse. You see it in their body shapes, their coat color, their temperament. But that’s just a tiny peak into their diversity. They are quite diverse in how the metabolize and react to drugs of all kinds. Those gene differences also account for varying drug pathways and how drugs affect them (for instance, why a Cytopoint injection might work only 2 weeks in one dog and 6 weeks in another). All us humans and our dogs are born with a few defective metabolic genes. But having just one good one in a gene pair usually allows metabolic and cell processes to proceed normally. The more inbreed the dog breed, the more likely it is that a pup inherits two bad ones at the same location. That is why some breeds (like French Bulldogs) suffer so much from skin problems. (ref)
Cytopoint neutralizes only one member of the IL-6 family of messenger molecules. A feature of the IL-6 family are redundant, duplicate and overlapping activities between its members. The system is very plastic. So with time, new pathways to itch might develop in your dog that decrease the effectiveness of Cytopoint. No one really knows. But sometimes, when monoclonal antibody drugs similar to Cytopoint loose their effectiveness, it can be regained by increasing the dose or frequency of the injections. (ref) At least for a while.
There are other things that you might mistake for a loss of Cytopoint effectiveness. Nothing will cause a dog to loose control more quickly than the sensation of a flea crawling around on its body. Dogs that are prone to allergies are almost always also allergic to flea saliva. So once bitten, those dogs will itch for hours. Doggy parks and places where lots of dogs frequent, shared quarters with indoor/outdoor cats, and backyard food sources for urban wildlife are all excellent ways to bring fleas into you and your dog’s life. Avoid them. Apoquel can also make a dog more susceptible to demodectic mange. I do not know about Cytopoint. But dogs on Cytopoint or Apoquel are not immune to catching sarcoptic - the itchy type of mange. Sarcoptic mange can be very hard to diagnose (with a skin scraping). So if either Cytopoint or Apoquel loose effectiveness you might consider three months of a monthly dose of Simparica® or one of its clones. It kills fleas, sarcoptic and demodectic mange.
In 2017, there should not be much of a difference. When dogs are heavy, Apoquel is often a bit cheaper when the dose is given once a day; when Cytopoint injections can be spaced farther apart and still give sufficient relief, it may be the less expensive option. If Cytopoint is being given every 3.5 weeks, its going to be more. Most of the time, the difference in price should not be great enough to influence your decisions. Go with effectiveness. Go with safety. Some folks go with Cytopoint because the think they won’t have to pay for the blood monitoring Apoquel requires. Cytopoint is a new kid on the block. Perhaps dogs on it can go with less monitoring; perhaps not.
This is just Zoetis’ current arbitrary pricing structure. It has nothing to do with production costs. If with time veterinarians and pet owners come to believe that Cytopoint is the better choice, its price will go up (or that of Apoquel will go down relative to it). Unfortunately, I do not know of any competitor products in development that would spur price competition (although Merial/Boehringer Ingelheim certainly has the expertise to produce a biosimilar).
Neither Zoetis, the company that makes both, nor the USDA or the EMA utter a peep about that in their published literature. They have just agreed to let drug rep, back alley talk establish trends. In an internal Zoetis report I do not have access to (C961R-US-13-051), of the 53 dogs receiving both Cytopoint and Apoquel over 42 days, only one was said to have had an “adverse event”. (ref)
I would not make a judgment on the beneficial effects of Cytopoint in your dog until after its third month’s injection. Particularly if it is transitioning from Apoquel. That is because dogs coming off of Apoquel often get worse for a short time. It is called a rebound effect and it appears to be due to the fact that compounds that built up or were suppressed by Apoquel in the itch cascade are freed to exert a stronger effect when Apoquel is no longer present. (ref) Many veterinarians attempt to get around that by discontinuing Apoquel slowly and overlapping the time that the dog receives both drugs. Some do that for a week, other a bit longer.
Many veterinarians dispense some Apoquel be kept around the house and given during “break-through” itching spells while on Cytopoint. That should be OK. But no one knows what the consequences of giving both drugs together for long periods might be. (they will if you send me your feedback).
Most dog owners ought to keep that as an option. At the least, such medications might stretch the poorer responding dogs to a full 4 weeks between Cytopoint injections. I know those extra treatments are a PIA to administer – a big chore for working families, older folks and those with big or obstreperous dogs.
Dog owners whose pet’s allergy issues are still seasonal might find either Apoquel or Cytopoint more effective when other medications are added during the height of the allergy season. Periods of stress and environmental changes that generate worry also intensify itch behavior in some dogs.
Your pet’s individual temperament is also a big factor - some dogs are more compulsive than others in their licking, scratching and grooming behavior. Those are the dogs that are likely to benefit most from the calming affect of antihistamines like Benadryl. Antihistamines have little to no effect on the itching of atopic dermatitis in humans, but they do help those folks sleep. (ref) I believe that is the case in dogs as well - the drug often exerts a sedative effect.
Some folks find that just wiping their dog’s foot pads off with unscented wet wipes after they have been outside reduces paw licking.
One can often get dogs with a breakout attack of itching through the problem using an Elizabethan collar. They bother dog owners more than they bother most dogs.
Many allergic dogs, especially those with floppy ears, need long term otitis control. Initially, they usually need a medication containing an antibiotic and corticosteroid. But later, a few drops of propylene glycol massaged down into each ear usually keeps the problem from flaring up again (propylene glycol is non-toxic, ethylene glycol is very toxic The Massengill Incident).
I have never been impressed with the effectiveness of allergy shots in dogs. But some folks swear by them. Perhaps they work in some dogs. Perhaps they might give added relief to dogs that aren’t help enough by Cytopoint or Apoquel. (ref)
Yes - there are two.
The one that’s already FDA approved is Sanofi/Regeneron’s Dupixent ® (dupilumab). Although, both Cytopoint and Dupixent are both produced in hamster cells, Dupixent has been fully “humanized” white Cytopoint has been fully “caninized”. (rptref1, rptref2) If you open my diagram at the top of this page, you will see that Dupixent block itch at a higher level than Cytopoint. It blocks the uncommitted (naïve) T-cells from converting to the Th2 cells that secrete IL-31. (ref) Because it works at a higher level than Cytopoint, it disables more of the factors responsible for itching. (ref) It is an injection given twice a month. In trials, it was about 25% better than the placebo in clearing up dermatitis. Giving the injection every week did not increase its effectiveness (ref) Dupixent seems most effective when topical corticosteroid ointments and lotions are also used. (rptref)
Nemolizumab is a drug even more similar in its effects to Cytopoint than Dupixent . It is currently undergoing human trials, but not yet approved by the FDA. Dermatologists just call it "Nemo". Cytopoint neutralizes IL-31. Nemolizumab prevents IL-31 from delivering its messages by plugging up (disabling) the IL-31 receptor docking stations on cells meant to receive those itch messages. Like Cytopoint, it is meant to be injected every 4 weeks. In the studies, 263 volunteers with atopic dermatitis were divided into two similar groups. When you discount the high placebo effect in the group that received the sham placebo treatment (the control group), 14.3% of those receiving Nemo had less scratching, and skin inflammation than the patients that did not receive Nemo. (ref)
In 2015, Bristol-Meyers Squib ran some human trials in England on a drug, BMS-981164. I believe was identical to Cytopoint in its intended action (an “Anti-Interleukin 31 Monoclonal Antibody”). (ref)
I believe they lost interest in developing it further since no mention has been made of the drug since then.