Numelvi (atinvicitinib tablets) is a once-daily oral JAK inhibitor approved by the FDA on February 25, 2026 for the control of pruritus associated with allergic dermatitis in dogs six months of age and older. It is the third JAK inhibitor to reach the U.S. veterinary market — after Apoquel (oclacitinib, Zoetis) and Zenrelia (ilunocitinib, Elanco) — and the first one labeled "second-generation," meaning it was designed to be more selective for the JAK1 enzyme while sparing JAK2, JAK3, and TYK2.

This article covers what the label says, how Numelvi differs from Apoquel and Zenrelia in practice, what the clinical trials found, what safety questions remain, and which dogs are — and are not — good candidates.

Fast answer

Numelvi is a reasonable first-line option for dogs with allergic itch who meet the label criteria (at least six months old, at least 2 kg, no serious infections). Its main differentiators are once-daily dosing from day one, label clearance for dogs as young as six months, and a JAK1-selective mechanism that may reduce off-target effects on blood cell production and immune function compared with older JAK inhibitors. The field safety data currently extends only to 28 days, and the long-term safety profile is still being established. It has not been evaluated with concurrent glucocorticoids, cyclosporine, or other systemic immunosuppressive drugs.

What Numelvi is and how it works

Atinvicitinib is a Janus kinase (JAK) inhibitor. JAK enzymes sit inside cells and relay signals from cytokines — proteins like IL-31, IL-4, and IL-13 that drive itch and inflammation in allergic dermatitis. When a JAK inhibitor blocks those signals, itch decreases.

There are four main JAK family members: JAK1, JAK2, JAK3, and TYK2. Each supports different biological functions:

Numelvi is described as "second-generation" because it is at least 10 times more selective for JAK1 than for JAK2, JAK3, or TYK2 in laboratory assays. For context, oclacitinib (Apoquel) has a JAK1-to-JAK2 selectivity ratio of approximately 1.8:1 — meaning it inhibits JAK2 nearly as potently as JAK1. Atinvicitinib's ≥10-fold selectivity is a meaningful pharmacological difference: it should interfere less with blood cell production (JAK2-dependent) and broad immune function (JAK3/TYK2-dependent). In practice, the clinical significance of that selectivity difference is still being evaluated in long-term post-marketing use. No head-to-head comparative trial between Numelvi and Apoquel or Zenrelia has been published.

FDA approval details

Dosing

The labeled dose is 0.8 to 1.2 mg atinvicitinib per kilogram of body weight (0.36 to 0.54 mg per pound), administered orally once daily with food.

Tablet sizes correspond to weight bands. Each tablet is marked with a letter (S, M, L, XL) for the four strengths. Tablets are scored and can be split.

Unlike Apoquel — which requires twice-daily dosing for the first 14 days before tapering to once daily — Numelvi is dosed once daily from the start. Zenrelia is also once daily from day one. The simpler dosing schedule matters for owner compliance: fewer pills per day means fewer missed doses.

Numelvi should be given with food. Oral bioavailability in the fed state is approximately 45.5% based on pharmacokinetic data in the FOI summary. The 0.8–1.2 mg/kg dose range was selected based on an IL-31 challenge model in dogs and pathway engagement assays that confirmed adequate JAK1 blockade at this exposure level.

Effectiveness

Two key clinical studies support the FDA approval:

Field efficacy study (289 dogs with allergic dermatitis)

This randomized, double-masked, placebo-controlled study enrolled client-owned dogs with moderate-to-severe allergic itch (PVAS score ≥ 6) at 26 U.S. veterinary practices. Dogs received either atinvicitinib at 1.0 mg/kg (range 0.8–1.2) or placebo once daily for up to 28 days.

Key results:

• By Day 7, 81.8% of atinvicitinib-treated dogs had a ≥ 2 cm reduction in owner-assessed pruritus visual analog scale (PVAS), compared with 46.5% of placebo-treated dogs (P < 0.0001).
• By Day 7, 30.5% of treated dogs had PVAS < 2 cm, corresponding to normal skin.
• By Day 28, 87.5% of dogs achieved at least a 50% reduction in itch or skin lesion severity, compared with 23.1% in the placebo group.
• Onset of action occurred within 2 to 4 hours of the first dose.

Atopic dermatitis-specific study

A separate randomized trial in client-owned dogs diagnosed with canine atopic dermatitis found similar results: Numelvi was well tolerated and led to significant reduction in allergy-related clinical signs, with the majority of treated dogs achieving meaningful improvement.

Vaccine response study

A study in healthy 6-month-old unvaccinated dogs demonstrated that Numelvi did not impair serological responses to multivalent modified-live vaccines (CDV, CAV2, CPV). This is notable because Zenrelia carries a label warning about vaccine timing — dogs on Zenrelia should not receive modified-live vaccines within two weeks of starting the drug. Numelvi's label does not carry that restriction based on the vaccine response data.

Safety profile

Field study adverse reactions (Day 28, N = 144 Numelvi vs. 144 placebo)

Diarrhea was actually less common in the Numelvi group than in the placebo group (4.2% vs. 10.4%). Bacterial skin infections were also less common (4.2% vs. 6.9%).

Three Numelvi-treated dogs withdrew from the study early due to adverse reactions (two for diarrhea), and two placebo-treated dogs also withdrew (both for diarrhea).

Laboratory abnormalities

Abnormal hematology results likely related to Numelvi included leukopenia, neutropenia, eosinopenia, monocytopenia, and lymphocytosis. Abnormal serum chemistry results included increased ALT, AST, and SDMA, and hypercholesterolemia. These findings are consistent with the mechanism of action of JAK inhibitors.

In the larger 289-dog field study presented at the European Veterinary Dermatology Congress, decreases in mean eosinophil, neutrophil, monocyte, and total white blood cell counts remained within reference intervals, suggesting reduced allergy-mediated inflammation rather than immunosuppression.

Neoplasia signal

No papillomas or skin masses were reported in the atinvicitinib clinical trials. This is relevant because neoplastic conditions (benign and malignant) have been reported in dogs treated with other JAK inhibitors. The Numelvi label includes a class warning about neoplasia risk, even though it was not observed in the Numelvi studies to date. Long-term pharmacovigilance data is not yet available.

Margin of safety study

In a 6-month target animal safety study, healthy beagles received Numelvi at 0×, 1×, 3×, or 5× the maximum dose daily. At 5× overdose, dogs showed a higher susceptibility to bacterial, fungal, and parasitic skin disease, consistent with the immunomodulatory mechanism.

Important safety warnings from the label

The FDA-approved label carries these warnings:

• Not for dogs under 6 months of age or with serious infections.
• May increase susceptibility to opportunistic infections, including demodicosis and interdigital furunculosis. Consider risk-benefit in dogs with recurrent demodicosis history.
• Neoplasia class warning: New neoplastic conditions have been reported with other JAK inhibitors. The label carries this as a class effect.
• Field safety data limited to 28 days. Long-term safety beyond 28 days has not been evaluated in a field study.
• Not evaluated in breeding, pregnant, or lactating dogs. Decreased mean testes weight was observed in a laboratory safety study, which is the specific finding behind this caution.
• Not evaluated with concurrent glucocorticoids, cyclosporine, or other systemic immunosuppressive agents.
• Persons administering the drug should wash hands thoroughly after handling.

Numelvi vs. Apoquel vs. Zenrelia: practical comparison

All three drugs are oral JAK inhibitors for allergic itch in dogs. They are not interchangeable — each has a distinct label, mechanism, and set of warnings.

What the selectivity difference means in practice

In vitro, Numelvi is at least 10 times more selective for JAK1 than for other JAK enzymes. The theoretical advantage: less interference with JAK2-dependent blood cell production and JAK3-dependent immune surveillance. In the clinical trials, hematology changes were mild and remained within reference intervals. However, "more selective in a lab assay" does not automatically mean "safer in a clinical setting" — that determination requires head-to-head comparative trials and long-term post-marketing data, which do not yet exist for Numelvi.

Beyond JAK inhibitors: the broader anti-itch landscape

Numelvi, Apoquel, and Zenrelia are not the only systemic options for allergic itch. Two other therapies are commonly considered:

• Cytopoint (lokivetmab): A caninized monoclonal antibody that neutralizes IL-31. Given by injection every 4–8 weeks. It does not suppress the immune system broadly — it targets one cytokine. No oral daily dosing, no JAK-related neoplasia warnings, and no laboratory monitoring requirements. It works well for many atopic dogs but does not address non-IL-31 itch pathways. No head-to-head trial between Numelvi and Cytopoint has been published.

• Atopica (cyclosporine modified): A calcineurin inhibitor that suppresses T-cell–mediated immune responses. Effective for atopic dermatitis but has a slower onset (2–4 weeks), requires careful monitoring (kidney function, blood pressure), and causes GI side effects (vomiting, diarrhea) in a meaningful proportion of dogs. It is not a JAK inhibitor and carries a different safety profile.

The choice among these options depends on the individual dog: age, comorbidities, owner preference for oral versus injection, cost, and the clinician's assessment of infection and neoplasia risk. A dog with a history of recurrent infections may do better with Cytopoint's targeted mechanism; a dog whose owner cannot manage regular veterinary visits for injections may prefer Numelvi's at-home oral dosing.

What the age difference means

Numelvi is labeled for dogs as young as 6 months. Apoquel and Zenrelia both require dogs to be at least 12 months. For a 9-month-old allergic puppy, Numelvi is currently the only FDA-approved JAK inhibitor option. For dogs over 12 months, all three are available and the choice depends on patient factors, cost, dosing preference, and vaccine timing considerations.

When Numelvi is a good fit

• Dogs ≥ 6 months and ≥ 2 kg with allergic dermatitis whose itch is not adequately controlled by topical therapy, flea prevention, or diet trial alone.
• Owners who prefer once-daily dosing and may struggle with the BID-to-SID taper required by Apoquel.
• Dogs due for modified-live vaccines where the Zenrelia timing restriction would be inconvenient.
• Dogs under 12 months of age who need systemic itch control — Numelvi is the only JAK inhibitor labeled for this age group.

When Numelvi is not the right fit

• Dogs with serious or active infections. All JAK inhibitors modulate the immune system and can increase infection risk.
• Dogs with a history of recurrent demodicosis. The label specifically flags this risk.
• Dogs currently on glucocorticoids, cyclosporine, or other systemic immunosuppressive drugs. Safety of concurrent use has not been established.
• Breeding, pregnant, or lactating dogs. Not evaluated.
• Dogs where long-term safety data is a priority. The field study data is limited to 28 days. Apoquel has over a decade of post-marketing experience; Zenrelia has less but more than Numelvi.
• Dogs with a history of neoplasia. The class warning applies to all JAK inhibitors.

Monitoring

The label does not specify a mandatory monitoring schedule, but based on the mechanism and clinical trial findings, the following are reasonable expectations:

• Baseline bloodwork (CBC, chemistry panel including liver values and SDMA) before starting Numelvi, especially given the observed changes in leukocyte counts, liver enzymes, and SDMA in the field study.
• Recheck at 2 to 4 weeks to assess itch response and tolerance.
• Periodic bloodwork for dogs on long-term therapy, consistent with monitoring practices for other JAK inhibitors.
• Watch for signs of infection: new or worsening skin infections, demodicosis, urinary tract infections.
• Watch for GI signs: vomiting, diarrhea, decreased appetite. These were the most common adverse reactions in the field study.

Questions to ask your veterinarian

If your veterinarian recommends Numelvi for your dog:

• "Has my dog been screened for active infections before starting?"
• "What bloodwork should we do before and during treatment?"
• "How quickly should I expect to see improvement?"
• "What should I watch for at home — and what warrants an immediate call?"
• "If Numelvi is not available yet at your clinic, what alternatives make sense while we wait?"

What Numelvi does not do

Numelvi controls itch associated with allergic dermatitis. It does not:

• Cure allergies. It manages symptoms; the underlying allergic response persists.
• Replace an allergy workup. Identifying whether the trigger is environmental (atopic dermatitis), food-related, flea-based, or a combination remains essential for long-term management.
• Replace flea prevention. Flea allergy dermatitis is one of the four main allergic dermatitis types. Adequate flea control must continue.
• Eliminate the need for recheck visits. Monitoring for infection, neoplasia, and lab abnormalities remains important on any JAK inhibitor.

Sources

• Merck Animal Health. FDA Approves NUMELVI (atinvicitinib tablets) for Dogs — Press Release, February 25, 2026. https://www.merck.com/news/fda-approves-numelvi-atinvicitinib-tablets-for-dogs-from-merck-animal-health-the-first-and-only-second-generation-janus-kinase-jak-inhibitor-for-the-control-of-pruritus-associat
• FDA Center for Veterinary Medicine. Freedom of Information Summary, NADA 141-596 (Numelvi). February 2026. https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadFoi/18155
• DailyMed. NUMELVI (atinvicitinib tablet) Full Prescribing Information. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4926fcfa-20a0-46d8-aca2-53ae88332a31
• dvm360. "FDA approves first and only second-generation Janus kinase inhibitor." March 2026. https://www.dvm360.com/view/fda-approves-first-and-only-second-generation-janus-kinases-inhibitor
• DermaVet Pro. "Numelvi (Atinvicitinib) in Dogs: 2026 Monograph." https://pro.dermavet.com/numelvi-atinvicitinib-in-dogs-2026-monograph
• Merck Animal Health. Numelvi product page — Selectivity, Safety & More. https://www.merck-animal-health-usa.com/hub/numelvi
• VCA Animal Hospitals. "Atinvicitinib." https://vcahospitals.com/know-your-pet/atinvicitinib
• Bonelli M, Kerschbaumer A, et al. "Selectivity, efficacy and safety of JAKinibs: new evidence for a still evolving story." Ann Rheum Dis. 2024;83(2):139–160. doi:10.1136/ard-2023-223850
• PMC (PubMed Central). "Anti-Cytokine Drugs in the Treatment of Canine Atopic Dermatitis." 2025. https://pmc.ncbi.nlm.nih.gov/articles/PMC12652870
• AAHA. "New canine itch medication: Interpreting label claims and warnings." October 2024. https://www.aaha.org/newstat/publications/new-canine-itch-medication-interpreting-label-claims-and-warnings