Three JAK inhibitors and two monoclonal antibodies now approved for canine atopic dermatitis

A dog comes in scratching, and the treatment could be a JAK inhibitor, a monoclonal antibody, cyclosporine, or prednisone.

The five drugs and how they work

Three JAK inhibitors are now FDA-approved for canine atopic dermatitis: oclacitinib (Apoquel, approved 2013), ilunocitinib (approved within the past two years), and atinvicitinib (approved within the past two years). Two monoclonal antibodies targeting IL-31 are approved: lokivetmab (licensed 2016) and tirnovetmab (licensed 2026). All five deliver antipruritic relief faster than cyclosporine or allergen-specific immunotherapy, and all five avoid the polyuria, polydipsia, and adverse-event risk that comes with chronic prednisone.

According to the source article, oclacitinib selectively inhibits JAK1 and JAK3 enzymes involved in allergy, inflammation, and pruritus (IL-2, IL-4, IL-6, IL-13, and IL-31), with little effect on JAK2, which is involved in hematopoiesis. The article reports that ilunocitinib is labeled as nonselective "with high potency for JAK1, JAK2, and TYK2." Atinvicitinib has high selectivity for JAK1 and is marketed as a second-generation JAK inhibitor.

Lokivetmab and tirnovetmab are both caninized monoclonal antibodies that bind and neutralize IL-31, though the exact binding site differs between the two. Both deliver antipruritic benefit within 24 hours. The source article reports that lokivetmab is labeled for dosing every 4 to 8 weeks, and tirnovetmab provides relief for 6 to 8 weeks "but can be dosed as often as every 4 weeks." In studies evaluating long-term lokivetmab administration, approximately 45% of dogs required dosing every 4 to 5 weeks, 40% every 6 to 7 weeks, and 15% every 7 to 8 weeks.

Selectivity and safety

JAK selectivity has become a talking point as ilunocitinib and atinvicitinib entered the market. Ilunocitinib's broader JAK2 activity theoretically raises concern for effects on hematopoiesis, and atinvicitinib's JAK1 selectivity is marketed as an improved safety profile. Cell and enzyme-based models are the source of current selectivity data, but ex vivo data are lacking and might produce contrasting results. In human medicine, selectivity is not yet a predictor of safety or efficacy, and the same holds in veterinary medicine. A patient's response to any JAK inhibitor depends on dose, pharmacokinetics, dosing frequency, target cell spectrum, and other factors.

One noninferiority study comparing ilunocitinib and oclacitinib for pruritus control in canine atopic dermatitis found ilunocitinib noninferior to oclacitinib. By day 84, the study found that "a significantly greater number of dogs in the ilunocitinib treatment group were determined to have achieved at least 50% reduction in pruritus" compared to oclacitinib (90% versus 72%). The study found that "clinical remission of pruritus, defined as achieving an owner-assessed pruritus score of less than 2 out of 10, was achieved in 77% of ilunocitinib-treated dogs versus 53% of oclacitinib-treated dogs." Investigator assessment of dermatitis "showed a statistically greater number of dogs achieving at least 50% reduction from baseline in the ilunocitinib group" compared to oclacitinib.

No published head-to-head studies compare atinvicitinib with either ilunocitinib or oclacitinib. Prospective studies comparing tirnovetmab and lokivetmab are also still needed.

Adverse events and pharmacovigilance

Oclacitinib has been the subject of independent studies and pharmacovigilance monitoring for more than ten years. A prospective open-label study evaluating chronic oclacitinib administration in allergic dogs ran for 630 days (mean 407 days) and the source article reports it showed "a positive impact on quality of life in > 91% of dogs and no serious adverse events attributable to oclacitinib." Over a five-year pharmacovigilance period evaluating "> 91 million dogs, the estimated frequency of adverse events was determined to be < 1 animal reacting per 10,000 animals treated," according to the article. The article reports that "reported adverse events for oclacitinib include vomiting, diarrhea, lethargy, anorexia, leukopenia, aggression, skin disorders not otherwise specified, and papilloma."

Current safety data for ilunocitinib followed dogs up to 112 days, and for atinvicitinib, up to 28 days. According to the source article, "the most commonly reported adverse events in dogs receiving ilunocitinib include gastrointestinal upset, lethargy, urinary tract infection, and anorexia." Dogs receiving atinvicitinib showed "gastrointestinal upset, otitis externa, hematuria, and bacterial skin infection," the article reports. Abnormal blood analysis findings (leukopenia, elevated liver values, hypercholesterolemia, and hypertriglyceridemia) have been reported with all three JAK inhibitors.

The product labels for all three JAK inhibitors "state that neoplastic conditions have been reported, but" make no claim that the drugs are associated with increased neoplasia risk, according to the source article. All three carry warnings about secondary infection risk.

The FDA issued a black box warning for ilunocitinib stating "that an inadequate immune response to vaccines could occur while receiving" the drug, based on "laboratory findings in vaccine-naïve puppies receiving" three times the labeled dose. The label recommends discontinuing ilunocitinib at least 28 days before vaccination and withholding it for at least 28 days after. A subsequent study evaluating "the serologic response after booster vaccinations in previously vaccinated dogs showed that ilunocitinib given at 3 times the labeled dosing did not significantly attenuate the serologic response" to adenovirus type 2, parvovirus, distemper virus, or rabies vaccines. The decision to continue ilunocitinib during vaccination should follow an informed discussion with the owner about the FDA warning.

Lokivetmab and tirnovetmab show comparable preliminary safety claims, with no restrictions on age or concomitant medications. Common adverse events for both monoclonal antibodies include "injection site sensitivity, dermatitis, bacterial skin infection, vomiting, diarrhea, and lethargy," according to the source article, though these are relatively infrequent. Several studies underscore "the long-term safety and efficacy of lokivetmab for the chronic management of canine atopic dermatitis, with no serious" adverse-event concerns. Lokivetmab appears to maintain consistent pruritus control in most patients, with up to 17% reporting loss of efficacy over time, and shows high client satisfaction and reduced need for other medications.

Prednisone use

Intermittent use of short-acting oral corticosteroids (prednisone or prednisolone at 0.5 to 1 mg/kg orally once daily, then tapered) is reasonable for "infrequent, acute allergic flare-ups up to 30 days," according to the source article. In a study evaluating client satisfaction while dogs were treated with prednisone or prednisolone, 70% of owners said "they were willing to pay more for a therapy" with fewer adverse effects. In the same study, 90% of dogs experienced "at least 1 adverse event by day 14, with polyuria and polydipsia" the most common.

Long-acting injectable corticosteroids are not recommended for atopic dermatitis treatment even in the acute setting. Long-term oral corticosteroid use carries "potential for adverse events including recurrent urinary tract infections, hepatopathy, diabetes mellitus, and cutaneous changes (poor hair coat, calcinosis cutis, comedones, cutaneous atrophy)," according to the source article. Topical corticosteroids ("hydrocortisone, triamcinolone, betamethasone, mometasone") should be used instead of systemic corticosteroids where possible "due to fewer systemic effects, although cutaneous atrophy as a potential adverse event" precludes long-term, consistent application. The source article states that "finding the lowest dose and frequency of steroids during chronic therapy is key to reducing the incidence of unwanted side effects."

More reads like this, free, weekly. subscribe to VeterinaryPracticeNow.

Cyclosporine and immunotherapy

According to the source article, "cyclosporine, a calcineurin inhibitor reducing the activity of T cells and IL-2, has been approved for the control of canine atopic dermatitis for over 20 years. It is effective and relatively safe for long-term control of canine atopic dermatitis." Cyclosporine "is not sufficient for acute flares of allergic signs," and "concurrent administration with a 3-week tapering course of prednisone (0.5 to 1 mg/kg" orally once daily) "is often recommended as cyclosporine takes time to effectively control atopic dermatitis (4 to 6 weeks)," the article reports.

Allergen-specific immunotherapy is a disease-modifying treatment option, in contrast to the other therapies discussed. JAK inhibitors provide rapid relief from pruritus compared to allergen-specific immunotherapy.

Practice implications

Practicing veterinarians now have multiple pharmacologic treatment options for atopic dermatitis cases. We're watching how practices weigh the clinical benefits of each option against the client's ability to afford ongoing treatment, because atopic dermatitis requires lifelong management and a therapy the client can't sustain won't control the disease. Oclacitinib's ten years of pharmacovigilance data give it a known safety profile, but the newer JAK inhibitors and the second monoclonal antibody offer alternatives when a patient doesn't respond or when an owner wants to avoid a specific adverse event. The dosing interval matters for compliance, and a monoclonal antibody dosed every six to eight weeks is a different client conversation than a daily oral tablet.

← Back to the Newsdesk