By Jon Plant, DVM, DACVD
Apoquel® (oclacitinib) is the new Zoetis drug for the treatment of atopic and allergic dermatitis in dogs at least 12 months of age. I’ve been prescribing Apoquel for almost 3 months now and I must say, wow, am I impressed with the efficacy! But, more on that another time. My purpose today is to summarize some of the safety data on Apoquel.
Apoquel is a selective janus kinase (JAK) inhibitor. JAKs are components of some cell receptors that receive instructions from other cells through molecules called cytokines. There are many cytokines (interleukins and others) and different types of JAKs. By selectively targeting some of those involved in the itch and inflammation of allergic and atopic dermatitis, Apoquel reduces itch and inflammation, while having less of an impact on other aspects of the immune system.
How does Apoquel do this? It exerts its inhibitory effect on JAK-1 and JAK-3 at lower concentrations than it takes to inhibit JAK-2. This is important because it allows the drug to target pruritogenic (creating itch) IL-31 and pro-inflammatory (IL-2, IL-4, IL-5, IL-6, IL-13) cytokines at concentrations lower than that at which it inhibits cytokines involved in hematopoiesis that are dependent on JAK-2 (IL-12, IL-23, EO, GM-CSF). It also means that we should follow the recommended dosing (0.4-0.6 mg/kg), even in those cases where it is not helping as much as we’d like. Apoquel is like fine wine. Too little leaves you wanting more, but too much will make your head throb. The key is to aim for the sweet spot where we are inhibiting the “bad” cytokines but leaving the “good” cytokines to do their thing.
Apoquel appears to be safe when given with other medications. The risk of metabolic drug-drug interactions due to Apoquel inhibition of hepatic CYP450 enzymes is low, as it has minimal inhibitory effect on canine CYP450 enzymes. The use of Apoquel concurrent with glucocorticoids, cyclosporine, and other immunosuppressive therapies is not recommended and hasn’t been investigated in any meaningful way so far. There have been some (about 30 I believe is what I heard from a Zoetis dermatologist) patients in a long-term continuation study that did receive glucocorticoids for one reason or another, and no issues arose (this is how I remember it, at least).
The manuscript describing this long-term continuation study (the mean time on study = 402 days as of May 2013) was in preparation the last I heard. A common concern expressed by veterinarians and pet owners alike is whether we know the long-term effects of this new drug. I suspect that we don’t know everything about it, but I do think that we know more than for most drugs that hit the market. When drugs are given to hundreds of thousands of patients after a drug is launched, uncommon adverse effects might turn up, such as toxicity due to a specific genetic mutation affecting its metabolism. That is why the FDA requires drug companies to perform pharmacovigilence, monitoring for adverse reactions after going to market. And why practicing veterinarians should take it upon themselves to report suspected adverse drug reactions.
More details in Part 2