My family’s dog, Rory, has always been weird. He will start screaming if, while running around the house like a maniac, he accidentally stubs his toe. He loves eating carrots. He gets jealous if two people are hugging and he isn’t included. He will only lie down on the softest pillow on the couch. He likes to sit on our laps after we’ve eaten dinner and flops over with wild abandon, confident that someone will catch him before he falls. He has been known to collect items such as books, shoes, and pencils in a particular corner of the living room. He is exceptionally food motivated and sometimes obnoxious in his relentless pursuit of affection.
Shortly after he came to live with us, we realized that he frequently suffered from pruritic, or itchy, skin. The inflamed skin was so itchy that he would scratch it until his hair was falling out in patches, and occasionally he would even make himself bleed. Our vet diagnosed him with canine atopic dermatitis, a fairly common skin disorder that is the result of an immune response to allergens in the dog’s environment. Atopic dermatitis is also common in cats, horses, and humans.
After we determined by switching him through a couple different dog foods that his diet was not the culprit, the vet did some blood tests that sought to identify which common allergens his antibodies were responding to. The results? In addition to being allergic to pollen from a number of local plants, Rory is allergic to human dander, i.e., us. Dander refers to the microscopic flakes of skin that we are constantly shedding (a 2011 study estimated that a single person sheds about half a billion skin cells every day). Human dander allergies actually aren’t all that uncommon in domestic dogs. Skin flakes are also one of the main components of household dust. In short, there is no practical way to protect Rory from exposure to these allergens, so we had to find another way to treat his condition.
We treated him with a number of different drugs, including antihistamines, oclacitinib (trade name Apoquel), and prednisone. Prednisone is a type of corticosteroid which works by suppressing the immune system. It is also used in humans to treat chronic obstructive pulmonary disease (COPD) and as part of some cancer treatment plans. Oclacitinib is a janus kinase inhibitor which helps to downregulate the expression of inflammatory cytokines. Cytokines are a broad category of small proteins that cells use to communicate with one another, and inflammatory cytokines are important to both normal immune responses and to inflammatory diseases like atherosclerosis, inflammatory bowel disease (IBD), and, in Rory’s case, atopic dermatitis.
The most effective of these treatments was the prednisone, but that had some unfortunate behavioral side effects, which is another way of saying that he started peeing on the carpet, harassing people for dog treats more often, and escaping the house to beg for treats from neighbors when we wouldn’t concede to his demands. Rory was physically a lot more comfortable in his skin, but also ended up spending a lot more time in the doghouse.
Then our vet suggested trying lokivetmab (trade name Cytopoint), a caninized monoclonal antibody that inhibits the activity of interleukin 31 (IL-31). Let’s break down what exactly that means. Monoclonal antibodies are antibodies created in a lab from modified immune cells and have a wide array of uses in biotechnology and medicine. “Monoclonal” means that these antibodies bind to a single specific part (epitope) of some particle (antigen). Antibodies exist in all multicellular animals, and it is not uncommon for scientists to modify an antibody created by cells of one species so that they can function in the immune system of another species. So you might, for example, use mouse cell cultures to produce an antibody designed to work with the immune system of a human; this would be known as a humanized mouse antibody. A caninized antibody is one that has been modified to work with a canine immune system. Finally, IL-31 is an inflammatory cytokine that plays a role in a number of inflammatory diseases, including atopic dermatitis. Like other cytokines, IL-31 needs to bind to specific receptors in order to promote inflammation. IL-31’s exact function in these diseases is not yet fully understood, but lokivetmab is designed to bind to IL-31 in the dog’s body and prevent the IL-31 molecules from binding to their receptors, effectively intervening in the inflammatory immune response that causes itching.
One upside of antibody therapy was that we only had to give Rory one shot every month, rather than a pill every single day. Rory is a very sensitive dog who does not enjoy getting shots, but he found them a lot more tolerable if he was also given a spoonful on peanut butter during their administration. Although you might expect lokivetmab to be a lot more expensive than other drugs we had tried, due to it being a biological molecule, the prices for a monthly shot of lokivetmab and a month’s worth of oclacitinib were actually quite comparable. The first dose of lokivetmab worked very well for Rory, but unfortunately the second dose that we gave him did not seem to have the same effect. Ultimately, we switched him back to oclacitinib for everyday use, with the occasional dose of prednisone when he has a particularly bad flare-up.
Although lokivetmab didn’t end up being the right course of treatment for Rory, it is still a fascinating medicine that provides a glimpse into the rapidly expanding field of biologic drugs for veterinary use.