A veterinary dermatologist's perspective JAK inhibitors

By Rebecca Parsiola, DVM, DACVD

With skin allergies accounting for the most common insurance claim for dogs for at least 13 consecutive years, and year-over-year increases in individual allergy-related claims for both dogs and cats,¹ effective allergy management is paramount for small animal veterinarians.

Atopic dermatitis results from complex interactions among the skin barrier, skin microbiota, and skin cell populations, ultimately leading to imbalanced immune reactions, specifically amplified pro-inflammatory T helper cell type-2 (Th2) immune responses to allergens.² Interleukins upregulated with Th2 responses include IL-2, IL-4, IL-5, IL-6, IL-13, and IL-31, which are responsible for atopic inflammation and pruritus.³

As there are no confirmatory diagnostic tests or pathognomonic clinical signs, atopic dermatitis can only be diagnosed after ruling out or addressing secondary infections, non-allergic conditions, flea allergy dermatitis, and cutaneous adverse food reactions.^3,4 Key historical features, including seasonal pruritus, onset of clinical signs between six months and four years of age, and response to antipruritic medications, may support a diagnosis of canine atopic dermatitis.⁴

While it is not always feasible, allergen-specific immunotherapy (ASIT) should be considered and discussed in all cases of atopic dermatitis, as it is the only available etiological treatment.^3,5 All other therapies manage the condition by masking the clinical signs. The mechanism of action of ASIT is poorly understood, but it is thought to reduce/prevent atopic flares by improving the balance between the T helper cell type-1 and type-2 immune responses and increasing the amount of T regulatory cells, which produce anti-inflammatory cytokines.⁶

The goal of ASIT is to reduce or prevent atopic flares, thereby decreasing the need for medical intervention.^3,5,6 Variable response rates are reported, but 50-100 percent are reported to favorably respond to ASIT.^4,7

The cited time between the initiation of ASIT and clinical response also varies. Clinical improvement may not be appreciated until the 12-month mark or longer, so owners are encouraged to consistently administer ASIT for at least this period.⁸ To maintain the patient's and owner's quality of life while awaiting clinical improvement from ASIT, antipruritic and anti-inflammatory treatments, as well as antimicrobials for secondary infections when present, are heavily relied upon.

Looking at JAK inhibitors

One of the most important recent advancements in medicine and tools for atopic dermatitis is the Janus kinase (JAK) inhibitor.

JAKs are cell-surface receptor-associated proteins that regulate the expression of specific cytokines and growth factors via enzymatic cascades.⁹ Simply, inhibiting the JAK mechanism results in blocking the transcription of certain genes, commonly interleukins, when discussing atopic dermatitis.

The JAK family has four members: JAK1, JAK2, JAK3, and TYK2. JAK1 appears to be most important for atopic dermatitis.¹⁰ In human medicine, wherein there are numerous medications within this drug class available, JAK inhibitors that preferentially block a set JAK are considered "selective," while those that block multiple JAKs are considered "non-selective."¹¹ Differences in selectivity affect safety and efficacy,¹¹ and higher doses have been demonstrated to reduce selectivity.^9,10

The JAK inhibitors available in veterinary medicine in the U.S. are oclacitinib, ilunocitinib, and, as of February 25, 2026, atinvicitinib.

Oclacitinib and ilunocitinib are U.S. Food and Drug Administration (FDA)-approved for the treatment of canine atopic dermatitis in dogs one year of age or older. Atinvicitinib is approved for use in dogs six months of age or older.¹² At the label dosing, 0.4 – 0.6 mg/kg by mouth every 12 hours for 14 days, then every 24 hours, oclacitinib is most potent against JAK1.^10,13 Ilunocitinib is reported to have high potency against JAK1, JAK2, and TYK2 at label dosing, 0.6 – 0.8 mg/kg by mouth every 24 hours.¹⁴ At label dosing of 0.8 – 1.2 mg/kg by mouth every 24 hours, atinvicitinib is 10 times more potent for JAK1 than JAK2, JAK3, and TYK2,¹² suggesting it may be the most selective JAK inhibitor available in veterinary medicine.

All JAK inhibitors have a rapid onset of action with improvement possible within hours, which distinguishes them from cyclosporine therapy.^4,13,14 Unique to oclacitinib is a chewable formulation, in addition to the tablet formulation.

Due to its recent release, there is little clinical information available about atinvicitinib, and there is limited head-to-head information comparing oclacitinib and ilunocitinib.

In a randomized, blinded trial comparing owner-assessed pruritus and investigator-assessed skin lesions at labeled dosing, scores were similar while oclacitinib was dosed twice daily.¹⁵ After day 14, when oclacitinib was reduced to once-daily dosing, both metrics were significantly better in patients receiving ilunocitinib than in those receiving oclacitinib. A proposed explanation is the reduced selectivity of ilunocitinib relative to oclacitinib.¹⁵

Similarly, reduced selectivity may explain why oclacitinib has proven efficacious, with immune-mediated and specific cancerous diseases, particularly lymphoma, when used at higher doses.^10,13 Oclacitinib has been used extra-label and yielded partial or complete remission in cases of the following: feline atopic skin syndrome, pemphigus foliaceus, ischemic dermatopathy, subepidermal blistering diseases, ulcerative ear tip dermatosis, hyperkeratotic erythema multiforme, inherited sensory and autonomic neuropathy, heritable neuropathy, idiopathic rhinitis,¹³ alopecia areata,¹⁶ reactive histiocytosis,¹⁷ proliferative and necrotizing otitis externa,¹⁸ eosinophilic furunculosis,¹⁹ canine perianal fistulae,²⁰ cutaneous lupus erythematosus,²¹ masticatory myositis,²² sebaceous adenitis,²³ cutaneous epitheliotropic T-cell lymphoma,¹³ lingual lymphoma,²⁴ and Sézary syndrome.²⁵ The majority of patients were prescribed greater than 0.6 mg/kg/dose and/or long-term twice daily dosing,^13,16-23 with relapses often seen with dose reduction.^13,16-18

Another important note is that higher dosing and/or long-term twice-daily dosing of oclacitinib is often needed in cats, owing to their accelerated absorption and elimination as well as increased plasma level variability.¹³

Important client communication

A valid veterinarian-client-patient relationship must exist for the prescription of extra-label medications. Also, this route should be reserved for cases in which on-label medications have been determined to be clinically ineffective, and patients would suffer without them. When considering extra-label prescription, clear communication with the owner regarding expectations, possible side effects, monitoring, and cost is required. Documenting that the owner understands their pet will receive a medication not approved for this specific use is also essential.²⁶

Currently, the only non-JAK inhibitor medications approved for canine atopic dermatitis are Cytopoint²⁷ and three forms of cyclosporine modified.²⁸ Currently, two formulations of cyclosporine modified are the only approved medications for feline atopic skin syndrome.²⁹

Baseline then repeat complete blood counts, serum biochemistries, and urinalysis are recommended for patients receiving JAK inhibitors, as mild leukopenia, more often neutropenia than lymphopenia, is the most common biochemical change of JAK inhibitors, but serum biochemistry and urinalysis abnormalities have also rarely been reported and are often transient.^13,30 Toxicosis with overdose, resulting in multisystem dysfunction and even failure, has been reported, particularly with the chewable formulation of oclacitinib, highlighting the palatability and importance of client education.³¹

While receiving JAK inhibitors, cats should be kept indoors to minimize the risk of infection with toxoplasmosis, which can be fatal, and raw diets should be avoided to prevent food-borne illness.³² Vomiting and diarrhea are the most common clinical signs seen with oclacitinib and ilunocitinib. Owners may also observe weight gain.¹³ Medications that inhibit JAK1/JAK3 reduce immune responses that prevent opportunistic infections and demodicosis, particularly with extra-label use, and patients should be monitored accordingly.^13,33

Similarly, these medications should be used with caution in patients with a history of neoplasia, but studies have shown that oclacitinib does not increase the risk of malignant or nonmalignant skin masses or lymphoma.¹³

Conversely, oclacitinib has been demonstrated to induce partial remission with some forms of neoplasia,^13,24,25 and JAK inhibitors are utilized in numerous human cancer treatment protocols.¹¹ Uniquely, ilunocitinib has a label boxed warning that advises discontinuation of ilunocitinib 28 days to three months prior to and 28 days following vaccination.³⁴ This is recommended due to the risk of inadequate immune responses to vaccines, but a more recent study has demonstrated that dogs receiving the labeled dose or three times the labeled dose of ilunocitinib for 56 days did not have attenuated serologic responses to CAV-2, CPV, CDV, or rabies booster vaccines relative to untreated control dogs.³⁵

While every immune system is different and much remains unknown about the long-term effects, particularly when used extra-label, JAK inhibitors can be an excellent tool to improve patient and owner quality of life when coupled with clear communications, careful monitoring, and intentional case selection.

Rebecca Parsiola, DVM, DACVD, earned her undergraduate degree from Louisiana State University and her Doctor of Veterinary Medicine degree from Louisiana State University School of Veterinary Medicine. She completed a rotating small-animal internship in Washington, D.C., followed by a dermatology residency at Dermatology for Animals in Phoenix, Ariz. Dr. Parsiola completed the Dermatology for Animals residency program in 2025 and earned veterinary dermatology board certification the same year. She is currently practicing at Dermatology for Animals in Rockville, Md., a Thrive Pet Healthcare partner.

References

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