Multimodal Management of OA in Companion Animals

B. Duncan X. Lascelles, BVSc, PhD, DACVS: We’ve been talking about multimodal approaches, and, yes, I think that’s an important aspect. There’s a burden on instigating treatments and cost. Regarding multimodal early management, what combination of modalities would you prioritize, Bryan?

Bryan T. Torres, DVM, PhD, DACVS-SA, DACVSMR: For dogs, I think primarily about weight management. I think about exercise—including low impact exercises—and things that I can do to maintain and build muscle mass, because the muscles are supportive structures around those osteoarthritic joints. I think about, potentially, supplements, and things like that which we talked about—polysulfated glycosaminoglycans, or things like that. And then, our nonsteroidals as being, really, the foundation as far as a drug therapy or pharmacologic.

B. Duncan X. Lascelles, BVSc, PhD, DACVS: I hadn’t moved to cats. Margaret, how would that differ, or would that be the same for cats, in your opinion?

Margaret Gruen, DVM, MVPH, PhD, DACVB: Many parts of it are the same. In consideration of weight management, obviously for dogs or for cats, it’s critical to control the pain. But, I think about it the way that I approach many behavior issues, which is that the medication, by itself, can’t do that much. You also have to have changes to the household and accessibility, the exercise, and the diet changes. The medication facilitates those. So, you use the medication to help get those secondary pieces in place, and then you can start to look at dose reduction. Can you take that dosage down now that we’ve got these other things going? If you can’t, then you stay on them longer or you stay on a lower dose. But that control of pain is critical to bringing those other therapies in.

B. Duncan X. Lascelles, BVSc, PhD, DACVS: Mark, you mentioned the adjunctive drugs. I think there’s consensus here in terms of the basic approach. When do you start to bring in those adjunctive drugs?

Mark Epstein, DVM, DABVP, CVPP: Well, this is easy. It’s like a slow hanging curve ball because we have 2 sets of guidelines that were produced by industry experts—one in North America, and the other one is global. So, there was the 2015 AAHA/AAFP Pain Management Guidelines for Dogs and Cats, and right about the exact same time was the World Small Animal Veterinary Association’s Global Pain Council Guidelines for Recognition, Assessment, and Treatment of Pain in animals’ guidance. When both of these taskforces looked at the totality of evidence in veterinary medicine, the 5 modalities that rose to the top, very clearly, were weight optimization, NSAIDs—arguably, grapiprant now—the polysulfated glycosaminoglycans, EPA-rich diets, and therapeutic exercise. Those were the 5. Until those have been buttoned up, I’m not going to necessarily turn to much of anything else. I may go quickly to those other things, but those things have to be under my belt before I go to gabapentin, or before I go to therapeutic laser, or something like that.

B. Duncan X. Lascelles, BVSc, PhD, DACVS: So, you’re really relying on those 5 modalities before considering…

Mark Epstein, DVM, DABVP, CVPP: Yes. That’s where the evidence is, right? If there was better evidence for gabapentin, maybe we put that up there; and the same thing with even acupuncture. It’s not that you can’t incorporate client values into that. If they don’t like the pharmacology side and they want to go ahead with acupuncture, fine. We do acupuncture in our practice. We have laser in our practice. I’m just saying that when it comes to triaging, where to focus the veterinary teams, their time and energy, and the clients’ resources, it has to be those5 things, first. Now, we will pretty quickly go to some of these adjunct pain-modifying medications if we’re not satisfied with that. And if we’re seeing a pretty debilitated patient, I may go ahead and throw that into the mix, out of the gate, as well. Gabapentin would probably be my top choice. Amantadine may be right up there, particularly if there’s any kind of neurologic comorbidity with it.

B. Duncan X. Lascelles, BVSc, PhD, DACVS: Now, Mark, there’s 1 drug you haven’t mentioned, which I’ve heard you talk about in the past—that’s tramadol. Is tramadol something we can rely on for analgesic effect in these sorts of patients?

Mark Epstein, DVM, DABVP, CVPP: No. The reason is because, on a pharmacokinetic basis, dogs simply do not make the opioid metabolite that is so common in people, and that’s why it’s a scheduled drug now. They make negligible amounts of that, so that’s just some mythology that needs to be busted right here, right now. Secondly, the overall bioavailability is very poor compared to people. There are low plasma levels. If you give it sequentially over time, those plasma levels disappear. It’s undetectable in some dogs. So, particularly for OA, to give it for an extended period of time, we should really have no expectation that it has any kind of significant pain modifying effect. I would caution that when people say, “Yes, but I dispense it, and my clients say it’s working. I think it’s working.” Well, we’re right back to that very first moment when we discussed that caregiver placebo effect. Does nothing work about 50% of the time?

Margaret Gruen, DVM, MVPH, PhD, DACVB: Right.

Mark Epstein, DVM, DABVP, CVPP: You could give placebo in cats. You could burn incense and they would look like they’re feeling better, because it’s 90% caregiver placebo effect there. So, no, for tramadol, orally, it’s not that it can’t work. With the parenteral version, there’s some data to support that it does. But, we don’t have that, here, in the United States. And really, we’re talking about oral tramadol in dogs. There should be no expectations of any clinical efficacy in OA.

Cats are a different story because there are pharmacokinetic and clinical data to support its pain modifying effect. They do make that opioid metabolite, and it has nice plasma levels and so on and so on.

B. Duncan X. Lascelles, BVSc, PhD, DACVS: But, I think on a practical basis…

Mark Epstein, DVM, DABVP, CVPP: Try to get it into a cat.

Margaret Gruen, DVM, MVPH, PhD, DACVB: Yes, exactly.

Bryan T. Torres, DVM, PhD, DACVS-SA, DACVSMR: That is the key.

B. Duncan X. Lascelles, BVSc, PhD, DACVS: Which I think is something. We haven’t touched on compliance. It’s very easy for us, as veterinarians, to make a diagnosis, although I think we struggle in making an early diagnosis of OA. But, we make a diagnosis and we write a bunch of scripts. Then, the owner has to go home and give these medications. Do you want to talk a little bit about how easy or difficult that is? How naïve are we?

Margaret Gruen, DVM, MVPH, PhD, DACVB: How naïve we are? It depends, certainly, on the cat, and it depends on the owner. But, it also depends on the medication. Is it bitter? Is it bulky? How difficult is it to get in? I think that there are some wonderful veterinarians making recommendations and watching owners give pills. They really know, and they’re not just saying, “Here’s some metronidazole. Go home with it.” But instead, they are watching owners give the medication and making sure that they feel comfortable giving it, and then are thinking about what the alternatives are for giving it. I think there’s a big issue of compliance when it’s difficult to get, but it also can be really damaging to their relationship. So, if you see one owner coming and the cat goes hiding under the bed, that really decreases both the human/animal bond and compliance dramatically. We have to think about the medications that are tolerated for administration—some of the ones that may taste better that we can give, or these ones that are on the horizon that may be injectable. That will be much easier for owners and for cats.

Sheilah Robertson, BVMS, PhD, DACVAA, DACAW: And I think it’s important to mention, especially with cats, the difficulty of medicating cats. There may be a good role for tramadol in OA in cats if it was palatable, but I think we can’t finish this discussion without saying that what a lot of people, then, do is have it compounded or turned into a transdermal gel. And assuming that that’s going to work, if we look at nearly every drug that has been effectively given by injection or orally, that then got compounded as a transdermal gel or some other thing, very few, maybe one out of all those drugs, have ever actually been proven to be efficacious. But, a lot of people, just to get around the issue, just have the transdermal products made and there are almost no data to support their use.