Apoquel vs Cytopoint vs Zenrelia: Choosing the Right Itch Drug for Your Patient

Matching the medication to your patient’s severity level

The itchy dog in your waiting room has options today that didn’t exist a decade ago. But with three targeted therapies now available for canine atopic dermatitis, a new challenge has emerged: which one do you reach for first?

The decision tree starts not with the drug, but with the dog in front of you.

Start With Severity, Not the Script Pad

The most common mistake? Jumping straight to systemic therapy without staging the case first.

Atopic dermatitis breaks down into three levels: mild, moderate, and severe. The treatment approach should match.

Mild cases (occasional flares, limited body regions) may respond to adjunctive therapy alone: omega fatty acids, barrier repair products, antimicrobial shampoos, and strict flea control. Many practitioners skip this tier entirely, but it’s worth trying, particularly when clients face financial constraints. Studies suggest adjunctive therapies can reduce itch scores by approximately two points on a 10-point scale.

Moderate cases need systemic intervention. This is where the targeted therapies come in.

Severe cases often require a methodical trial of different monotherapies before considering multimodal approaches.

The Players: How They Work

Cytopoint (lokivetmab) is a caninized monoclonal antibody that targets interleukin-31, a key mediator of pruritus in dogs.¹ It’s given as an injection every four to eight weeks. Label data shows adverse events limited to injection site discomfort, with a safety profile comparable to saline placebo.¹ Important caveat: Cytopoint controls itch only. Published data shows it does not prevent skin lesion development from the underlying inflammatory process.

Apoquel (oclacitinib) is a selective JAK1 inhibitor that blocks multiple inflammatory and pruritic pathways.² It works fast, with studies showing efficacy comparable to steroids within four hours of administration. Approved for dogs 12 months and older.

Zenrelia (ilunocitinib) is the newest entry, a JAK1/JAK2/TYK2 inhibitor with once-daily dosing from day one.³ Unlike Apoquel, there is no loading dose period. Published head-to-head data from Europe showed Zenrelia was not inferior to Apoquel, with some measures of pruritus and skin lesions showing significantly better control.³

Watch for the Apoquel Rebound

Here’s something that catches many practitioners off guard. Data from a study of 20 dogs showed that almost 45% experienced worsening pruritus between days 14 and 28 when transitioning from twice-daily to once-daily Apoquel dosing.

“The label says give it BID for 14 days, then drop to SID. But almost half of dogs flare during that transition. If you’re not warning clients about this, they think the medication stopped working.”

The same study found that concurrent short-course prednisone (days 1 through 4) reduced the rebound rate to 15%. In practice, extending the BID phase and considering a short steroid course if flares occur is preferable to preemptively combining drugs.

Monotherapy First, Combination Second

For severe cases, the principle is clear: exhaust monotherapy options before combining drugs. If a patient hasn’t tried cyclosporine or Zenrelia as standalone treatments, combination therapy is premature.

The reasoning:

• Combination therapy is off-label
• Additive adverse events are a real concern
• Additive cost is significant (Apoquel plus Cytopoint can run $170/month for a medium-sized dog versus substantially less for monotherapy alternatives)

Don’t forget adjunctives even in moderate-to-severe cases. Fatty acids, barrier repair products, and antimicrobial therapy reduce how much systemic medication you need and can drop itch scores by an additional two points.

The Zenrelia Vaccine Question

Zenrelia carries a boxed warning regarding vaccination. The label was updated in late 2025 to remove earlier language about “fatal vaccine-induced disease.” The current warning addresses the potential for inadequate immune response to vaccines and recommends discontinuing the drug 28 days before and after vaccination.

However, published data complicates this picture. A study using previously vaccinated dogs (a more realistic clinical scenario than the original naive-dog study) showed no statistical difference in titer development at one and three times the label dose compared to control animals.

The original study raising concern used vaccine-naive dogs with concurrent coccidiosis, confounding the results.

Practitioners should review the current FDA label and published literature to make informed decisions for individual patients.

Practical Takeaways

1. Stage the severity first. Don’t reach for systemic therapy on a mildly affected dog.
2. Warn about Apoquel rebound. Days 14 to 28 are a vulnerable window. Extend BID dosing or consider a short steroid bridge if needed.
3. Cytopoint controls itch, not inflammation. It won’t prevent skin lesions in dogs whose rash is driven by the underlying disease.
4. Try monotherapy before stacking. Exhaust individual drug options before combining.
5. Stay current on Zenrelia’s label. The vaccine guidance has evolved. Review published data and current FDA recommendations.

The goal isn’t finding the “best” drug. It’s matching the right drug to the right dog at the right time, and setting expectations so clients understand what success looks like.

This post is based on a VetOnIt CE webinar by Dr. Jason Pieper, DACVD. For RACE-approved dermatology CE, visit our On-Demand Library.

References

1. Gober M, Hillier A, Vasquez-Hidalgo MA, et al. Use of Cytopoint in the Allergic Dog. Front Vet Sci. 2022;9:909776. PMID: 35928119.

2. Gonzales AJ, Aleo M, Mahabir S, et al. Oclacitinib (APOQUEL) is a selective Janus kinase 1 inhibitor with efficacy in a canine model of flea allergic dermatitis. J Vet Pharmacol Ther. 2024;47(6):447-453. PMID: 38926932.

3. Forster S, Trout CM, Despa S, et al. Comparative efficacy and safety of ilunocitinib and oclacitinib for the control of pruritus and associated skin lesions in dogs with atopic dermatitis. Vet Dermatol. 2025. doi: 10.1111/vde.13319.

4. Pieper J. Canine Atopic Dermatitis: A Case-Based Approach. VetOnIt CE Webinar, 2025.

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