As Janus kinase (JAK) inhibitors have continued to rise in popularity in human medicine, they are beginning to move into the veterinary industry. In 2024, Zenrelia became the second JAK inhibitor to hit the veterinary market for controlling pruritis and inflammation in canine patients with atopic dermatitis. As they continue to rise in popularity, how much do we know about them and their effectiveness in treating patients?

During his “Do you know JAK? How Janus Kinase inhibitors work and how they have been game changers for the treatment of canine atopic dermatitis” Andrew Rosenberg, DVM, DACVD, explained to attendees the background on atopic dermatitis and its treatments, plus how the JAK inhibitors are providing relief to the itchy patients in your clinic.

Atopic dermatitis is usually characterized by its excesses itchiness and is caused by the skin’s reaction to allergens in the environment. For dogs, these allergens are absorbed through the skin, unlike humans who inhale the allergens, but atopic dermatitis is a lifelong condition, so effective treatment is crucial to improve quality of life for these patients.

According to Rosenberg, when it comes to atopic dermatitis, the first issue is an atopic dog has a genetic predisposition to atopic dermatitis, which can lead to a defective skin barrier. Because of this, more allergens can get through the skin, causing it to become degraded by bacteria and dust.

“When I have an atopic dermatitis dog, these are my goals. My first goal is to treat any secondary skin infections because I want to prevent recurrent infections. So I mentioned a minute ago that dogs with atopic dermatitis already have this defective skin barrier, so they're more predisposed to infection. We all know this. You currently see secondarily infected dogs with allergies every day in our practice. So cytology, bacteria, and yeast, we treat the infection, the popular therapy with antimicrobials when needed,” Rosenberg explained to attendees.

The second goal for Rosenberg is to decrease the itching to make the pet more comfortable. Rosenberg explained that it is important to determine the underlying condition of the allergy because if the patient presents to the clinic with a nonseasonal allergy, he is going to do a food trial to make sure there are no food allergies and if it appears seasonal, an allergy test would make more sense for determining the allergy. Treating atopic dermatitis has traditionally been done through multiple therapies such as shampoos, rinses, mousses, Cyclosporine, and Corticosteroids for example.

 Now, the market also has access to JAK Inhibitors, such as Apoquel, and now Zenrelia.

JAK inhibitors, as Rosenberg informed the group, were named after Janus, the Roman god with 2 faces because they work by taking a partner to function. Rosenberg explained that the JAK inhibitors are in a group of tyrosine kinases, and the receptors on this cell family act as signal pathways for multiple cytokines, growth gats, and hormones. The group is made up of 4 members, JAK1, JAK2, and JAK3, and, to make things confusing, said Rosenberg, tyrosine kinases 2, or TYK2.

“Each JAK to function takes on a partner. So JAK1 may partner with JAK3, JAK2 can partner with another JAK2, but to a function, they take on a partner, and that process is called dimerizing…they dimerize according to each other, so 2 of them, and they're kind of the gateway of cells,” Rosenberg explained.

Rosenberg also shared that Elanco conducted a head-to-head study on the safety and efficiency of Zenrelia and Apoquel for submission within the European Union. The study was double-blinded and randomized with 338 client-owned dogs that were confirmed to have atopic dermatitis. The study showed researchers that one dose of Zenrelia a day is at least as effective as the market incumbent JAK inhibitors on the market at the endpoint on Day 28.3 When the product proved reliable at the assessment from the owners on Day 28, it continued to Day 112. For the duration, the itch on average with the Zenrelia patients was below 2 on the visual analog scale.

“So why is that important? Two is considered to be a normal level of itch in these individuals. So when we look at the proportion of dogs with a great visual analog scale for less than 2 on day 112, 77% of the Zenrelia dogs achieved that and 53% of the Apoquel dogs achieved that. Both are great drugs… both have a rapid decrease in itch. We see this small uptick in itch on day 14, when Apoquel dosing, goes from twice daily to once daily, but there was a higher number of dogs with Zenrelia that had lower than 2 on that very visual analytic scale.

Because every case of atopic dermatitis will be different, it can be helpful for clinics to have more than one JAK inhibitor on site. Rosenberg explained that JAK inhibitors have different endotypes, which is a term used for a variety of diseases where the patient is going to be a little bit different for the cytokines that cause the clinic signs presenting.

Rosenberg A. Do you know JAK? How Janus Kinase inhibitors work and how they have been game changers for the treatment of canine atopic dermatitis. Presented at: 2024 New York Vet Show; November 7- 8, 2024; New York, NY.

Cornell University College of Veterinary Medicine. Atopic dermatitis (atopy). Cornell University College of Veterinary Medicine. Published February 23, 2023. Accessed November 14, 2024. 

https://www.vet.cornell.edu/departments-centers-and-institutes/riney-canine-health-center/canine-health-information/atopic-dermatitis-atopy

Elanco Announces FDA Approval and Launch of Zenrelia™ (ilunocitinib tablets), Offering An Effective, Safe Solution in Canine Dermatology. News release. Elanco Animal Health Incorporated. September 19, 2024. Accessed November 19, 2024. 

https://investor.elanco.com/press-releases/press-releases-details/2024/Elanco-Announces-FDA-Approval-and-Launch-of-Zenrelia-ilunocitinib-tablets-Offering-An-Effective-Safe-Solution-in-Canine-Dermatology/default.aspx

Articles

Andrew Rosenberg, DVM, DACVD, provided an overview of Janus kinase inhibitors for treating canine atopic dermatitis

Are Janus kinase inhibitors a JAKpot for allergy relief?

Veterinary dermatologist Andrew Rosenberg, DVM, DACVD, explains the effectiveness of JAK inhibitors for treating canine atopic dermatitis

Video interview with Andrew Rosenberg, DVM, DACVD

My name is Andrew Rosenberg, I am a veterinary dermatologist. I work with the Animal Dermatology Group as a clinical dermatologist in both the Wayne, New Jersey, and White Plains, New York, offices. I’m also the director of medical operations for the entire group, which is the largest dermatology group in the world. Additionally, I’m the president of the American College of Veterinary Dermatology, so I’m involved with the organization that board-certifies all veterinary dermatologists.

So it's a good question. And, you know, there's now 2 JAK inhibitors in veterinary medicine on the market. The first, of course, was Apoquel, and that was a Jak inhibitor. And now there's a new drug that was recently approved called Zenrelia, which is now the second JAK inhibitor on the market because Apoquel [has] been out for for considerably longer, there are some studies that that show that long-term, Apoquel is as effective as a medication like cyclosporine for long term, and it actually works more rapidly and Zenrelia works. You know, similar speed of onset as Apoquel does. So for long term treatment of allergies, or I should say allergy symptoms, because that's what these medications are treating, they're treating the symptoms of allergies, they're as effective as cyclosporine, and in a head to head study for Zenrelia versus Apoquel, well, they were, they were, you know, Zenrelia had a little bit better, even improvement in a periodic visual analog scale long term, when the study was extended long term, and it was shown to be non inferior than Apoquel

They're very effective at treating, you know, itch and associated with allergic dermatitis and inflammation associated with allergic dermatitis. Certainly another treatment of allergies is steroids, right? And we try to avoid long-term steroid use because of the side effects. So, but as far as your question is, how effective are they? Well, yeah, they're effective, and they work well. If we're talking about, kind of the flip side of this, which is the best long-term management of atopic dermatitis, as well as those JAK inhibitors work, I'm still recommending allergy testing and immunotherapy for long term control, and then I use those JAK inhibitors to really control the itch while I'm waiting for my immunotherapy to work, and then I can use them as needed if there are flare ups, despite being on immunotherapy, which inevitably there, there are, very commonly, some flare ups here and there.

Videos

Andrew Rosenberg, DVM, DACVD, discusses the effectiveness of JAK inhibitors for treating allergy symptoms in animals

How effective are Janus kinase inhibitors? 

In this episode, Anne Chauvet, DVM, DACVIM, CHT-VT, shares insights with our host Adam Christman, DVM, MBA, and listeners from her extensive career treating neurological conditions. 

Chauvet also explores the importance of distinguishing clinical symptoms from radiographic findings in disc disease, especially in prone breeds, the complexities of brain tumors in aging dogs, highlights MRI as a key tool for precise diagnosis, and more throughout the episode. 

: The big thing I tell veterinarian, just remember, when you're thinking about brain tumors, they don't usually happen unless you have a certain age. Now, I'm going to have a caveat in that that the youngest one I've had was 3 1/2 year old with a little Jack Russell, but usually it's 4 years and older. So if you have a 2 1/2 and a half year old little dog that begins seizuring, so therefore has a cortical lesion in the brain, the odds of that being a brain tumor are pretty darn low to none. If you have a 9-year-old pit bull, you have a much greater chance of having a brain tumor over idiopathic epilepsy. So you're going to make your decisions on whether you work up or not, or how far you can push your client for that. So the signs you're going to see are dependent entirely on the anatomy. So if I section out the brain, the front is going to be usually seizures. 

The cortex is very prone to seizure, particularly in what we call the Piriform lobe, which is the part of the brain that on each side of the brain will turn around, curl towards the midbrain that's very prone to seizure, and it's a lovely place for gliomas to launch themselves in all those pit bulls, Bulldogs, they tend to have a lot of gliomas. Boxers famous for it as well. So that's an area that often gets seizures. Then you look at things like midbrain, we see a lot of midbrain problems with pituitary tumors. Those are more of the dog that's very dull, aimless walking is going to kind of start running into things that often people label it for senility. Be careful with that senility label, because if you overlook it. It might be too late for us to be able to help the patient.

Podcasts

Anne Chauvet, DVM, DACVIM, CHT-V, takes listeners into the world of veterinary neurology 

The physical exam approach to the neurologic patient

Neil Mittelman, DVM, DACVIM, offers his top 3 tips for conducting a neurological exam

Advice for veterinarians doing a neurological exam, from a veterinary neurologist

 delivers expert-led veterinary continuing education on your schedule. With 

, you can access top-tier sessions anytime, anywhere—whether at home, in the clinic, or on the go. Ready to earn CE credits? Watch this session and more on 

During the Fetch dvm360 Conference in Atlantic City, New Jersey; Neil Mittelman, DVM, DACVIM, sat down with 

 to talk about his lecture “Neurological Examination from Head to Tail.” During the interview, Mittelman also offered his top 3 tips for veterinarians that are conducting a neurological exam.

So, the biggest thing is to be as thorough as possible and try and evaluate all the important parts of the examination.

But also, to get an accurate history is part of that. The neurological examination needs to be performed in its entirety, but also not to forget their basic physical examination, because a lot can be garnered in terms of information for ultimately making a diagnosis, having known what their vital parameters are and what the history was from the owner.

The last thing is not to get overly intimidated by doing a neuro exam. You know, even the concept of performing a neurological evaluation can be overwhelming for owners, for their pets, and for clinicians alike, and sometimes it doesn't fit into a tiny box of ‘this problem is x’ or ‘this problem is y,’ so to be as thorough as possible, not to forget the basic thorough examination that we do normally, and to try and be as thorough as possible, but if you can't put a bow on it and say exactly what it is, just to write exactly what you see. That's the best we can do, and then we put that information together.

Neurological exam pearls, from a veterinary neurologist

The American Heartworm Society (AHS) has updated their Feline Heartworm Guidelines for veterinarians. The guidelines—last revised in 2015—addresses persistent underdiagnosis and undermanagement of heartworm disease in cats, and provides more robust data on prevention, testing and treatment, according to AHS.

The guidelines update was spearheaded by a committee of AHS board members. The revisions were completed after a thorough scientific review by experts from the fields of parasitology, cardiology, and clinical practice. It includes revised advice on heartworm screening, mosquito control and treatment options for heartworm-positive cats.

Feline heartworm disease can be life-threatening. It starts with a bite from a mosquito infected with the parasitic worm 

allowing heartworm larvae to enter the cat’s bloodstream. The larvae thrive and develop in subcutaneous tissues before moving into muscle tissues, the heart, lungs and arteries.

Immature worms’ arrival into the small arteries in the lungs initiates a severe inflammatory response that damages not only the arteries, but also the bronchioles (small airways) and alveoli, according to Cornell University College of Veterinary Medicine in Ithaca, New York. “Between 60 and 100 days after the initial infection, you can start to see signs of pathology in an affected animal’s body, even though the parasite has not yet reached maturity,” Dwight Bowman, DVM, PhD, a professor of parasitology at Cornell, said on the university’s website. 

The revised AHS guidelines recommend routing heartworm screening for cats. The 4 primary reasons for screening, according to the AHS, are as follows

to help establish a diagnosis when a veterinarian finds clinical evidence of infection;

to monitor the status of cats already diagnosed with heartworms;

to establish a baseline prior to beginning a heartworm prevention product;

and to better understand the relative risk of feline heartworm in a practice area.

“While dogs are routinely screened for heartworms during annual check-ups, testing in cats has primarily been limited to cases when a veterinarian suspects heartworm infection based on a cat’s clinical signs,” Jennifer Rizzo, DVM, president of AHS, said in a news release.

 “With so few cats tested, it has been difficult for veterinarians to get a handle on the true incidence of heartworm in cats—even though cats are at risk wherever heartworm infection occurs in dogs.”

According to the revised guidelines, cats should be screened using both antigen and antibody tests. The AHS further recommends that veterinarians conduct antigen tests with heat-treated serum, which differs from their canine guidelines. Heat-treated serum dissociates potential antigen-antibody immune complexes and helps obtain the most accurate results. The second component of heartworm screening in cats is antibody testing.

Other diagnostic techniques outlined in the revised guidelines include radiography, echocardiography and point of care ultrasound.

 “There’s no question that testing limitations have been a significant factor in heartworm underdiagnosis in cats,” Rizzo acknowledged in the release. “By using the most accurate screening procedures and screening cats on a more routine basis, we hope to greatly improve the veterinary profession’s understanding of the disease 

initiate steps to best manage affected patients.”

With more routine testing, the AHS says its experts expect the numbers of cats diagnosed with heartworms to increase. Treatment objectives are to relieve the clinical signs of disease and, in the case of adult infections, to prevent sudden death of the cat.

 “While no approved adulticide treatment is available for cats, our guidelines include updated recommendations for managing infected cats,” Rizzo said.

Several classes of medications, along with dosages, are described in the revised guidelines, from anti-inflammatory drugs to leukotriene modifiers to antibiotics, according to AHS. Techniques for surgical removal of adult heartworms are also described in the revised guidelines.

Meanwhile, the AHS guidelines continue to recommend that all cats be on year-round heartworm prevention with a macrocyclic lactone product. However, the revised guidelines now also address the importance of vector control as well as preventive products. The goal of vector control in cats should be to reduce the risk of mosquitoes in the environment rather than on cats themselves, according to AHS.

“As an organization dedicated to reducing the incidence of heartworm disease and its impact on pets, the AHS has long been concerned about the underdiagnosis and undermanagement of heartworm disease in cats,” Rizzo said. “Fortunately, we now have scientific information that supports a more proactive approach to heartworm diagnosis, as well as greater specificity in prevention and treatment approaches.”

The revised guidelines can be accessed on the AHS website at 

American Heartworm Society announces updated guidelines on management of feline heartworm disease. News release. American Heartworm Society. November 12, 2024. Accessed November 13, 2024. 

https://www.heartwormsociety.org/in-the-news/910-american-heartworm-society-announces-updated-guidelines-on-management-of-feline-heartworm-disease

Cornell Feline Health Center. Heartworm in cats. Cornell University College of Veterinary Medicine. Accessed November 13, 2024. 

https://www.vet.cornell.edu/departments-centers-and-institutes/cornell-feline-health-center/health-information/feline-health-topics/heartworm-cats

Last revised in 2015, the document provides guidance for addressing underdiagnosis and undermanagement of the disease, as well as fresh data on  prevention, testing and treatment

American Heartworm Society updates feline guidelines

Mark J. Acierno, DVM, MBA, DACVIM, shares different medications available, as well as other management strategies, for appetite stimulation and nausea relief in feline patients with chronic kidney disease

Managing chronic kidney disease symptoms in cats

What options are there for controlling nausea and stimulating the appetite of a feline patient with chronic kidney disease? In an interview with 

 discussing his lecture “Improving the Lives of Feline Patients with Chronic Kidney Disease,” presented at the Fetch dvm360 conference in Atlantic City; Mark J. Acierno, DVM, MBA, DACVIM, professor and associate dean at Midwestern University, talked about different methods for controlling these symptoms in cats, breaking these methods down into management strategies, and different medications that can be used.

There's a number of different things we can do. And so part of it, you know, I like to break it down into both… management and then medications.

And so, for the management, things like small, frequent meals, rotating the diet. You know, often what happens is we will send a cat home with a particular brand of cat food, and the owner will tell me ‘well they ate it for a while, then they stopped.’ And so what I do is I send them home with a whole smörgåsbord. I just come to rotate it, right? Just keep rotating through the different ones.

Small, frequent meals. It may mean, you know this idea of feeding a meal in the morning and a meal at night may have to be changed, because when we're sick, we don't feel like eating a big meal, right? And so, cats may nosh during the day, and that may add up to a meal, and that would be great.

Mark J. Acierno, DVM, MBA, DACVIM, shares different available options for appetite stimulation and nausea relief in feline patients with chronic kidney disease