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Additional Options For your Dog That Are Still In Development

CADI - Canine Atopic Dermatitis Immunotherapeutic injection

Ron Hines DVM PhD

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4/24/16 update: CADI is now available to selected certified veterinary dermatologist throughout the United States.

Yes

The process that causes your allergic dog to itch is very complex. I'll try to explain it as simply as I can. It involves many of the pet’s internal messenger compounds interacting with the cells that constitute its immune system.  Drug companies attempt to design custom compounds, like Apoquel, that prevent these messenger compounds (cytokines) from activating cells (the resident monocytes=macrophages) involved in producing the itchy sensation. However, these natural messenger compounds (in this case the interleukin cytokines) in your pet have good as well as bad functions and in the process or treating the bad effects (like skin allergies), there is the possibility that the good functions can be affected as well. That is the reason that the ads you see on TV for human drugs similar to Apoquel (like Xeljanz) list a lot of possible side effects at the end of the commercial. These drugs are called JAK-inhibitors. The chemical name for those on the market today all end in –nib (like oclacitinib, tofacitinib, etc ).

There is another approach.... A “designer” antibody can be created at the pharmaceutical company that acts farther downstream – thus (hopefully) sparing the pet many of the potential side effects of blocking itch earlier in the process. Perhaps it might also be used in addition to a drug like Apoquel to lower the dose or enhance its effectiveness.  That type of “designer” antibody is also called a monoclonal antibody or mAb. They are the latest and most spectacular breakthroughs in human drug development. Those compounds, like Humira (adalimumab)‎‎ all end in –mab.  MAbs are very sophisticated, very pin-point in their accuracy, and hopefully less likely to cause side effects because they target a single chemical message (in this case,the one to itch). The approved human-use ones are also extremely expensive.
 
Its not only dogs that develop atopic (allergic) dermatitis with itching; people do too. Scientists cannot tell you why one person has this problem any more than veterinarians can tell you why your dog developed this problem. But in both cases, the cause is most often, a complex combination of genetics and environment. 

Over the last 15 years, laboratory mice have been developed that allow scientists to learn what is occurring within the body that is the root of the itching. (ref) Those studies tended to implicate one specific leukotriene messenger , Interleukin 31, as the underlying cause of itching. (ref1, ref2, ref3) There are differences between humans and dogs - for one, in humans the gene for its production is on chromosome 12 , in dogs, on chromosome 26.

It is possible for pharmaceutical companies like Zoetis to create a “designer” mAb to reduce IL 31. But I had assumed that the cost of producing such a compound would prohibit their use in your dog (in humans, $12,000- $15,000 per year for Remicade). I was wrong, on August 3 ,2015, they announced trial studies of a mAb designed especially for allergic dogs. You can read their press release here and a second announcement here.

Things that work in theory or in the laboratory do not always pan out in real life. I follow another mAb in development to treat human Alzheimer’s disease. Veterinarians do not have any medicines that halt or reverse mental decline in old dogs either and I was hopeful that that new drug might offer some hope to dogs as well as people. (ref) But although the real-life human test results released by Biogen in March, 2015 were quite optimistic; by July, they were considerably less so. Let's hope Zoetis is successful, we need all the options we can get !

Humans also get atopic dermatitis. So there is a great deal of interest in the underlying mechanism that cause itching in us as well (ref) . Monoclonal antibody drugs like CADI that target IL-31 that are currently in human trials are lebrikizumab , tralokinumab and baricitinib. Because these drugs are designed to coexist with the human immune system ("humanized"), my understanding is that they would be of no value to our pets. The only one in development that might work in various species is apremilast. But all of these medications are far more expensive than most pet owners could afford.