Cytopoint Not Working?

Ron Hines DVM PhD

  You can let others know how Cytopoint® worked for your dog if you send me an email

Allergic skin disease is one of the most frustrating problems dog owners and veterinarians face. If you include the milder cases, allergic skin disease/canine atopy affects ~10-15% of the dogs in the developed world. (read here,   here  &  hereZoetis’ Cytopoint® is a dramatic leap forward in expanding your dog’s treatment options. In the majority of dogs, it will dramatically reduce a pet’s itching.

However, there will always be a few dogs that show less improvement than we desire (=partial responders), and others like the Labrador retriever in the photo that showed early improvement that fizzles with successive injections (non-durable responders). There will also be a few dogs that show little if any improvement at all. That is because the itch process is so complex and can go wrong at so many levels. (read herehere)   

Here is one email I received:

My dog Gatsby is a neutered male Black Lab/Springer Spaniel. He is 7 yrs old. He received his first Cytopoint shot in July of 2019. It was amazing. He completely stopped itching in 12 hours. That 1st Cytopoint® injection gave him relief for 5 months. But the 2nd shot didn’t produce as quick an improvement as the first shot. It’s Feb a week after the shot and he’s still licking his feet and groin and biting his toes every day. He was on Apoquel for 2 years before we adopted him from the rescue. At the time he had severe allergies, ear infections, licking, biting, bare spots, super-oily smelly skin. Also air licking. Gatsbys records said he also had severe anxiety.  He has had no infections since we’ve had him on Cytopoint. It seems Cytopoint is the better of the two medications. ​We were bathing him daily at first, now 2x a week. But now he is no longer responding to Cytopoint at all. He gets only minimal relief after the injection. I had heard about the possibility of developing antibodies to the drug which our holistic vet thought had happened. She put him on a low dose of Apoquel. That doesn’t seem to help much while trying different Chinese herbs. We didn’t continue getting Cytopoint although our local vet wanted to still give it even after it didn’t work well which is confusing to us because of the antibody talk. I know you can’t answer questions about individual pets but could you let me know whether in general you’ve ever heard of other dogs having a good response after a poor one? Would it be worth it to try again in a dog with that sort of response or just assume he has developed antibodies? Maybe its because he came to us with severe anxiety too. Sorry to bother you with this and if it’s something you don’t usual answer or can’t due to legal restrictions I understand.  Just thought to ask. I called Zoetis but they weren’t able to give me an answer.

Learning From Physicians

I described Gatsby’s problem to a group of human dermatologist who study Dupixent®. Like Cytopoint, Dupixent (dupilumab) is also a monoclonal antibody. It is approved to treat allergic dermatitis (atopy) in people. These three research dermatologists had also noticed that some people benefit greatly from the drug. But a subset of patients only obtain partial relief from their itching (“partial responders”). And another group got sufficient relief from the first few shots but, with time, the dupilumab gave less and less relief (“non-durable responders”). The comparison of Dupixent’s effects in humans with Cytopoint’s effects in dogs is not a perfect match – but it does give us some insights. Cytopoint® blocks the actions of an inflammatory cytokine, IL-31, while Dupixent® blocks the actions of two other inflammatory cytokines, IL-4 and IL-13.

This is the treatment flow chart the physicians produced:

Their first thought was that Gatsby had produced anti-drug antibodies (ADAs) against Cytopoint®. Read about antibodies targeting other antibodies here and here. ADAs are thought to be the most common reason that injections of monoclonal antibody medications over time cease to be helpful. That occurs in approximately 20% of humans taking dupilumab to combat their allergic dermatitis. (read here) If Cytopoint® should lose its effectiveness in your dog, Apoquel®, being a very different type of medication (a nib), will probably still be effective. (read here)

If neither Cytopoint® nor Apoquel® is effective, your dog’s scratching may not be entirely driven by allergies. Be sure your pet is thoroughly checked for bacterial or fungal skin infections, psychosomatic or separation anxiety tendencies, sarcoptic mange, the slightest exposure to fleas or overgrown toenails. Much rarer possibilities are atypical ringworm,   leishmania,   hypothyroidism or too much cortisol  = hyperadrenocorticism.    

Dogs do occasionally suffer from behavioral dermatitis. Veterinarians generally treat those issues with SSRIs like Reconcile® (aka Prozac®) or clomipramine (Anafranil®). Acepromazine, besides being calming, has some antihistamine properties as well. (read here) Even mirtazapine, commonly given to dogs and cats as an appetite stimulant, sometimes has anti-itch effects. (read here)

How Long Should I Wait Before Deciding If Cytopoint® Is Going To Be Helpful?

One initial monthly Cytopoint® injection, given correctly, should be sufficient to make that decision, two at the most. But stop immediately if the shot(s) appear to have made the situation worse. If that occurs, it is often due to “blossoming” of a skin staphylococcus or yeast infection. Long term or repeat antibiotic administration to control staphylococcus generate antibiotic-resistant staph which are then also a threat to you and your family. (read here)

Should Cytopoint® disappoint you, don’t neglect a two-month trial on a hypoallergenic hydrolyzed protein diet such as Purina’s H/A®, Hills z/d® or Royal Canin’s HP®. Contrary to what these diet manufacturers will tell you, the vast majority of itchy dogs don’t itch because of a food allergy. Dogs with food allergies generally exhibit it with gastrointestinal upsets and diarrhea. But it’s always worth a try. 

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