Are Janus kinase inhibitors a JAKpot for allergy relief?

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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.

Understanding atopic dermatitis

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.² Now, the market also has access to JAK Inhibitors, such as Apoquel, and now Zenrelia.

JAK inhibitors

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.

References

1. 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.
2. 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
3. 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