I thought we'd start off 2023 talking about a product for osteoarthritis in horses, pentosan polysulfate sodium (we'll just call it pentosan from now on). A new, FDA-approved formulation has just been released in the United States, although it's been available in Australia and a few other places since the 1990s.
NOTE: You might have been giving your horse a pentosan product already. There have been compounded formulations of pentosan available for some time in the United States. Compounded drugs are not the same as FDA-approved drugs, although the horse drug market is flooded with compounded products. Compounded medications are the subject of another article, but suffice it to say that if you've been giving pentosan to your horse, depending on where you live, it's production may be more or less regulated, that is, you may be more or less sure that you're getting pentosan in your pentosan. If you want to try the new, FDA-approved product on your horse, you'll have to get it from your veterinarian.
WHAT IS PENTOSAN?
Pentosan is an ester (a chemical term) that's made up of a chain of sugars (known as polysaccharides). In this case, the sugars are called pentoses, that is, they contain five carbon atoms. None of this is particularly important to horse owners (or veterinarians, for that matter), unless you love chemistry, but at least you now know why it's called pentosan (from pentoses).
In its chemical action, pentosan is similar to a class of drugs known as low molecular weight heparins. In people, heparins are used to prevent blood clots, and to treat stroke and heart attacks. In horses, heparin was once tried for treatment of laminitis, but it didn't pan out. This is mostly relevant to you because heparin inhibits blood clotting, and bleeding is a side effect of pentosan (more on that in a bit).
HOW DOES PENTOSAN WORK?
Well, begging questions such as, “If” and “How Well” (more on that in a bit), frankly, it's still a bit of a mystery of pentosan might work for osteoarthritis. Oh sure, there are lots of entirely optimistic proposed mechanism, such as increasing production of hyaluronic acid (which is thought of as a sort of joint lubricant) and increasing production of cartilage components (known as glycosaminoglycans), and maybe it helps prevent enzyme destruction of cartilage, and perhaps it affects the production of cytokines (which are just substances secreted by some cells that have effects on other cells).
Heck, maybe it even sops up free radicals, those dreaded compounds that are said to damage about anything they come in contact with (in the simplistic way of looking at the compounds that seems to be pushed by Dr. Google). But the fact is, nobody really knows how pentosan works for the treatment of osteoarthritis, if in fact it does much at all. To me, this is annoying, because I like to have some idea of how something really works before I give it to a horse. Call me cranky.
WHAT IS PENTOSAN USED FOR?
There is a pentosan pill available for humans. In humans, pentosan may be prescribed to relieve the bladder pain that's caused by a condition known as interstitial cystitis. There, it apparently works by preventing bladder wall irritation. For what it's worth, interstitial cystitis is apparently not a big problem in horses, although it apparently does occur. I've never seen a case.
Of course, the big news in animals – especially insofar as advertising and sponsorship goes – is that it's yet another option for the treatment of osteoarthritis. Interestingly, in humans, pentosan is NOT approved for the treatment of osteoarthritis, in spite of some early evidence which concluded it was helpful (CLICK HERE) which, to me anyway, is curious, because if you want to make a lot of money for a successful treatment for arthritis, there's no better place to start than the human market. That fact is a bit of a red flag for me when it comes to pentosan for osteoarthritis in horses (and dogs, too).
NOTE: Apparently, there are now clinical trials being conducted on pentosan in humans. It will be very interesting to see the results of these trials.
WHAT'S THE CLINICAL EVIDENCE?
While it's been tried in humans – to no avail, apparently, insofar as getting drug approval, and in spite of a couple of studies that showed “promise” – pentosan has been occasionally tested on horses (and dogs, too). For example, it's been reported in an influential book on equine arthritis that a group of racing Thoroughbreds who had chronic osteoarthritis were given pentosan in the muscle once a week for four weeks and that signs of joint disease were “improved” but not eliminated.
In another study, nine horses that got pentosan in an experimental arthritis model had improvement in the quality of their joint cartilage (but we don't know if they got any better – CLICK HERE to see the study). Finally, in another study, a product containing pentosan and a couple of other things didn't do much of anything when administered to horses (CLICK HERE).
Since, sadly, there's not really much robust clinical evidence for the effectiveness of pentosan (after, oh, nearly 30 years), perhaps it might be instructive to ask veterinarians who have been using the stuff what they think. Or, maybe not. I've asked a couple of friends who practice(d) in Australia and one thinks it's wonderful, while the other things it's akin to pouring water on their back. But rather than just rely on two conflicting opinions, in 2014, a survey of 76 Australian veterinarians was published (CLICK HERE) Here's a summary of results
- Pentosan was most commonly used as prophylactic therapy prior to competition (80.3%). NOTE: That's right along the lines of the rationale typically used for a bunch of horse products intended to help joints. That is, “We don't know if it will do anything, but it might help.”
- Pentosan was considered by 48.2% of respondents to have high efficacy. NOTE: That also means that 51.8% of respondents thought that the product didn't do much, which is right along the opinions of the two people that I asked.
- The most common dose regimen for prevention and treatment of OA was 3 mg/kg, intramuscularly, once weekly for four weeks followed by monthly injections. NOTE: That's a combination of the manufacturer's recommendation plus some unknown dosing schedule, which, again, is just like what's used for many other products. First, the products are dosed according to the label, and then, they're given on some other schedule that's often dictated by how much the medication costs. Otherwise stated, you don't really know what you're doing, but at least you're doing something, if you can afford it.
- Most respondents (78%) combined PPS with other drugs for treatment of OA. NOTE: That's not much of a ringing endorsement for the effectiveness of the product.
- For treating OA, 83% of respondents considered a combination product was more efficacious than pentosan alone. NOTE: This was a curious finding, especially since the research that I previously cited showed exactly the opposite (CLICK HERE).
- The most common reason not to use this combination was cost. NOTE: That makes a good deal of sense, actually. It's fine to spend money on your horse but if it doesn't seem to do much, why bother?
SO, WHAT ABOUT THE EVIDENCE THAT GOT THE DRUG APPROVED?
In spite of the previous (underwhelming) evidence, the fact of the matter is that pentosan did get approved by the US Food and Drug Administration, so the evidence had to show something. This is where you have to dig into the evidence a little bit. I did, and here's what I see, based on the drug summary, which you can see if you CLICK HERE.
The manufacturer of the new product did a field study, that is, they were using horses at barns, stables, etc. They ended up with 109 horses that got a shot of pentosan in the muscle once a week for four weeks, and 113 horses that got an injection of saline once a week for the same period (that's according to the recommended dosing regimen).
All of the evaluated horses were lame, and they were graded by the lameness scale developed by the American Association of Equine Practitioners:
- 0: Lameness not perceptible under any circumstances.
- 1: Lameness is difficult to observe and is not consistently apparent, regardless of circumstances (e.g., under saddle, circling, inclines, hard surface, etc.).
- 2: Lameness is difficult to observe at a walk or when trotting in a straight line but consistently apparent under certain circumstances (e.g., weight-carrying, circling, inclines, hard surface, etc.).
- 3: Lameness is consistently observable at a trot under all circumstances.
- 4: Lameness is obvious at a walk.
- 5: Lameness produces minimal weight bearing in motion and/or at rest or a complete inability to move.
So, what were they measuring? The metric for improvement was a change of one level on the AAEP scale. For example, perhaps a horse was lame at the walk initially (grade 4) but after the medication, he was only lame all the time at the trot (grade 3). I guess that's something, but it's not much, in my opinion. In fact, I rarely hear clients congratulate me, saying, “Great doc, after treatment, now he's less bad!” Plus, add that to the fact that the measurement was subjective (“Is he a bit better?”) and the relatively small number of horses (relative to the large trials often conducted in human medicine, that is), and there's some reason to wonder how meaningful the metric really is.
But how about the results? Well, according to the study, 57% of the horses that received pentosan improved. Of course, 36% of the horses that got saline also improved. That's a difference that is statistically significant, that is, it's somewhat less likely (although not impossible) that the results occurred purely by chance.
But there are larger questions that can't really be answered by this study. In fact, you're probably the best person to answer them. Specifically:
- Is the relatively modest possibility of mild improvement worth the cost?
- Do the results, even if true, really mean anything (that is, are they clinically relevant – I don't think that they're likely to be, but I'm pretty conservative)?
- Are the possible side effects worth the risk (more on that, below)?
WHAT ABOUT SIDE EFFECTS?
I'm glad you asked. If you want to give your horse pentosan, there are some side effects you should be aware of. In fact, the study documented several of them, including:
- Increase in measures of blood clotting (which you'd probably expect in a heparin-like product)
- Lethargy
- Behavior changes
- Colic
- Stiffness
The effect on blood clotting is real. As a result, I'd probably avoid giving it immediately before your horse is going to do something potentially traumatic (like run, jump, or spin). I'd probably also avoid giving it to a horse that might need surgery. Oh, and, just in case you have blood clotting problems yourself, and since pentosan is an anti-coagulant, if you take an anti-coagulant, you should take care not to inject yourself, or maybe even have someone else do it.
WHAT'S THE BOTTOM LINE?
Frankly, I'm not very impressed. To be fair, I'm pretty conservative, so I'm rarely an early adopter. That said, first of all, this really isn't a new drug – it just finally got approved in the US after being available for nearly 30 years in other countries. Experimental reports – including the one that got the drug improved – aren't particularly robust, that is, you shouldn't expect to see a great improvement, if you see improvement at all. In addition, pentosan is also NOT a pain-relieving medication. The idea that the product might prevent arthritis is mostly just naïve optimism, although, as with other products, and as per the Australian survey, it's probably the number one reason that people will use pentosan.
You'll probably see lots of advertising coming up in the next few months – perhaps you'll even see sponsorships show up at horse shows. Hopefully, I've given you plenty of information with which you can start to make up your own mind.
Dr. David Ramey is a vocal advocate for the application of science to medicine, and—as such—for the welfare of the horse. Thus, he has been a frequent critic of practices that lack good science, such as the diverse therapies collectively known as “alternative” medicine, needless nutritional supplementation, or conventional therapies that lack scientific support.
This article original appeared on Dr. Ramey's website, doctorramey.com and is reprinted here with permission.
The post Ramey: A New Pentosan Drug For Horses Was Just FDA-Approved; What Does It Mean For You? appeared first on Horse Racing News | Paulick Report.
Source of original post
