Hello everyone, and thank you for taking the time out to watch this webinar on topical therapy, in canine atopic dermatitis presented by Dr. Tim Nuttall. Thank you, Tim, for giving up your time tonight, to present to us.
Also thank you to the webinar vet, for, all the hard work that gets put in, to, to, to, to, to helping us organise these webinars. We also want to give you some information about Duxo S3, and we'd love to give you lots of information about Duxo as a brand, where Duxo S3s come from, etc. But we don't want to to take up too much time with the webinar.
So what we've actually done is we've got a short video that's played. Right at the end, which will actually give you hot off the press information about in field trials, and Tim will allude to in his webinar about how a lot of topical products, dermatopicals have maybe lacked this in the past. So DuxO S3 is obviously leading the way.
But also there's a lot of other information on top of that, and we've actually provided you with a link which you'll get an email or will be on the on the homepage of this webinar where you can click through into various folders where there's information from our symposium ASPD. There's 3 short videos to really give you. Dux and DuxO S3 and our new active ingredient in Fiream in a nutshell, but also all our abstracts and field trial results.
The videos are by myself, Andrew Fullerton, the product manager for Duxo S3, but also two of them are by Emily Foelberg, who's our technical manager at Siva. And just to introduce Tim. Tim Nuttall should need no introduction really, but he qualified from Bristol University in 1992.
And very soon after that, moving to Edinburgh University to study as a dermatologist and do a PhD in KA atopic dermatitis. After that, he joined Liverpool University and developed a very busy, bustling dermatology clinic there before in 2013, moving back to the Edinburgh Vet School, and he's there now as head of veterinary dermatology. And he's written hundreds of clinical and scientific publications as well as books.
He's lectured all over the world. He serves on various scientific committees and also has a big passion for antimicrobial resistance. So he's an absolute superstar.
And again, Tim, thank you so much for putting this talk together. I know I'm going to learn a lot of Of of good nuggets of information. After the talk, we'll shoot a short video and then actually there's questions with Tim afterwards.
And if you do have any other specific questions, please do feel them back to us via webinar vet. Hi, everyone, and thanks again for giving up your evening. It's a lovely pleasant summer's evening, in Edinburgh, where I am.
So thanks for coming indoors and watching or listening to this live, rather than waiting, for the recorded version a bit later on. Sorry about the technical issue, at the beginning. I hope I didn't say anything too embarrassing.
I think we and, Anti and I were just wittering about how, tiring and exhausting everything is at the right, right now. I hope everybody is, is safe and well. Just like to point out that, if you're, well, I, I suppose we're actually getting advice calls from all over the world, to be honest, but, you, we, we're still available, for business as it were.
So we're still taking advice calls. We'll do the best that we can to help people, with doing telemedicine. I was saying to Anthony earlier, I'm showing my age a little bit in that I'm not adapting totally to, to telemedicine.
I still like the old fashioned, seeing the client and seeing the animal. If you're local to us in Edinburgh, we're still open for cases. We're trying to do as much as we can remotely, and, and through your practises, but there's anything that you think is urgent, essentially you're just not comfortable with, do get in touch with us and we can make arrangements to, to see cases.
safely and, and observing social distancing and so on. And in fact, I was in the clinic, this morning with, with some rabbits, believe it or not. So what I'm going to do, this evening is go through, looking at skin diseases, mainly atopic dermatitis, partly because that's one of the most severe chronic and, and intractable things that we see.
We also talk a little bit about infection, and really concentrate on the topical treatment side of things, which sort of matches with, with SIA's launch of the new Duxo, that's how you pronounce it, S3 range of products. And I, I should point out, at this point that very grateful to Siva for sponsoring this evening's webinar. And that as a conflict of interest warning, I have received, lecture fees, research, funding, and, and other support from SIA, within the last 5 years, but also from alanco, the back.
ICF. I act actually forgotten the others, but quite a lot anyway. I should have prepared that one, more thoroughly.
Right, on to the main, thrust of, of tonight's talk. So, this is a, a, a sort of complex wheel or looking at the, the process of atopic eczema. So, so, it.
Oops, let's just get a laser pointer up. There we go. So AE here is atopic eczema, which is effectively, pretty much the same disease.
It's very, very similar to atopic dermatitis in dogs. And I, I love this definition because I think it just gets away from aetiology and allergy and just says what it is, which is, which is this, this immune, mediated skin disease. That is reversible but not curable.
And I love this wheel because it just shows how we get all these factors, so the, the barrier damage, the, the allergic sensitization, the, the chronic, changes, impact of the environment, changes to the microbiome, triggering of innate immune, mechanisms, and the genetic background and all of these contribute to the clinical signs that we see. But this doesn't imply. Causality, it doesn't imply where an individual comes into this cycle.
And it also allows us to say, well, some of these factors are going to be more important in some individuals than others and we really have to treat this as a, as a very individual disease. And this is a similar, the somewhat less elegant, way of putting it, that, that we've developed in dogs and the, and the central overlapping Venn diagram here refers to the allergic sensitization. And atopic dermatitis, that's, that's the disease with the environmental allergen, sensitivities.
And I've purposely not overlapped this with atopic like, dermatitis, because there's no. Environmental allergen sensitivity here, but we can have concurrent food allergies. So these, for example, you could have an animal that has house dust mite allergy and food, or one or neither, and then in heavy, heavily flea endemic areas, a lot of the atopic dogs are concurrently flea allergic.
But then we also have all the non-allergic mechanisms, so anxiety certainly plays a big role in human eczema. It's probably underrecognized in dogs, environmental factors. Skin barrier, innate and adaptive inflammatory pathways, and then, and then what's becoming more and more important is the skin and possibly the gut microbiome, in atopic disease as well.
And it really, this, this isn't the same disease, certainly between breeds and between individuals in certain breeds, and this is, taken from A paper that looked at a very large number of atopic dogs of different breeds and basically the more red and yellow an area, the more likely it is to be affected by atopic dermatitis, and the more blue or white, the less likely it is. So the boxer, golden retriever, Dalmatian, French Bulldog, Labrador, Jack Russell Terrier here, all very much fit that pattern of extremities, ears, ventral body, flexor surfaces. But if you look at the Westie, the German Shepherd dog and the Sharpei, actually they have quite a different presentation, suggesting it's not quite the same disease, in those breeds.
And then. So it could have different factors and this one size fits all treatment is, is, is probably a mistake. We have to be much more individualised with that.
And then certainly chronic, sorry, acute and chronic disease are very different. The immunological background of the disease, and the relative importance of different factors like skin barrier, innate immunity, different itch pathways, microbiome, skin, and allergen sensitization and so on are quite different in this dog to this dog where we've got, extreme, a much more severe disease, with some severe chronic change taking place and the management approaches. To this has to be different.
And one way to look at this is we need to get this dog to this dog and then keep this dog like that. And you know, just as an aside here, this dog is not a suitable candidate, for topical therapy. It's not a suitable candidate for immunotherapy by themselves because they'll have very little impact at this stage of the disease, whereas this dog, they, they could have been much more important.
One important factor is, is, is to look at what we now call proactive therapy. And as I said, really, what we're doing here is getting that, that severely affected dog, either with severe acute changes or severe chronic changes, is another German Shepherd dog with, with, with, with severe chronic ectopic dermatitis. And our initial, programme of therapy is to treat that very aggressively, get it under control.
And then in the past, what we were guilty of, and, and this is possibly driven by the fact that we didn't have a lot of highly effective medication that was suitable for safe long term treatment is we would back off and then wait till there was a flare, and then we would treat the flare and so on and so on. Now what happens here is we're only treating the tip of the iceberg and we're missing the chronic ongoing inflammatory changes, which is what leads to these very chronicly affected dogs and then ear canals, for example, this is what leads to the chronic end stage here that needs a tea. So what we're looking at now is proactive therapy rather than this reactive therapy.
We get the dog under control. So. We take it from here to here and then we've got to get this dog onto a long term programme of treatment that may Tames the flares and prevents this drive to chronic disease.
Now, again, there are so many different permutations and treatment options now in KI ectopic dermatitis that, you know, it's impossible to do this justice in, in one lecture since you aren't going to concentrate on the, on the topical treatment options, because I think this is a really useful. Area of therapy. There have been lots of recent advances in this.
It is the mainstay of first line, first baseline level of treatment in atopic eczema. Everything builds on from that. And you could argue that it's perhaps easier to, to concentrate on washing and bathing ourselves than, than in a dog.
There are a lot of factors now making this more straightforward. And it, it's certainly recommended now as a baseline therapy, in both the 2010 and 2015. International Committee on allergic Diseases in Animals treatment guidelines.
And this, diagram is borrowed from Siva. It's part of their S3, range, and it, but I think it's quite useful because it does emphasise that you have for topical therapy, that the, the skin barrier, you then have the skin microbiome and then you have the skin immune system and all of these are, are working together. And they're all important both in health and disease and whatever we do with this skin, we really want to try and address all of, all of those three areas and that's what I'll try and do, this evening.
Traditionally, we, we used to use shampoos, you, that you could well argue that these are the most effective form, certainly of cleanser. That they're most effective in terms of being able to distribute the active ingredients, to the coat as well as get rid of the allergens and irritants and so on. But certainly they are, much more time consuming.
Than other modalities and so and so recently that's led to other products. Excuse me, which, have been designed to be easier. Mainly these are non-rinsing preparations, so it removes some of the time consuming, and, and, and, facility consuming, efforts with, with shampooing.
But you could argue that apart from maybe wipes, none of these are going to have that same physical cleansing and perhaps moisturising, activity in the skin compared to bathing. Another really important part that, that's been forgotten, perhaps a little bit, and this is where we talked tend to talk about topical products being very safe, is that it, it, it, that needs to be proven. And one of the problems that we have with, with most, not all, but the vast majority of topical products is that they are, they're not medicines.
So the regulation is a lot lighter touch, than we would, we would see with, with medicines. And I've had my eyes opened a little bit recently. To how little regulation there is for a lot of non-medicines, food additives and medical devices.
I was really quite shocked considering what we use these for. And this one study here that was reported, in the veterinary record, last year, I think, we were saying this is really important because the owners are being exposed to, to, to these things as well. And this is, an on I I maybe it's not uncommon actually.
We see this with a, with, with some frequency, at least we get advice calls on this to some frequency. And I borrowed this slide from Jan de Klerk, who's a good friend and a dermatologist in, in Belgium. And cause he's, that's much, much better picture than than mine.
And this is post bathing fromchiosis, and this tends to occur where you have over vigorous bathing against the lie of the fur coat, which is called, which causes micro trauma to the hair follicles. This is particularly common in short-coated dogs, coupled with pseudomonas contamination of the water supply and all the shampoo. And this is an incredibly painful disorder.
And the last two cases that I've seen were actually both referred in as, as emergencies to our neurology service with back pain. They, they were so painful, so that's something to watch out for as well. So to start off with, I'll look at, you know, what we've loosely, I, I, I guess, termed initially as the sort of skin barrier care side of things.
So if we're looking at treating atopic dermatitis in terms of repair skin barrier repair. And the shampoos and, and again, what's surprising really is is the lack of evidence that we have that proves some of these products work. So I would differentiate here.
Products that have some evidence to show that they work. It's not always the best quality evidence, but at least there's some evidence to show that they work against those where the efficacy is, is claimed with no evidence at all. And really, at this stage, I'll talk about S3 later on.
This is the old D so calm range. A dermatopic, which is a German shampoo, and I don't even know that that's still available. Alamil and Duxocalm were the only three, with, with some evidence that they reduce pruritus.
And it, it possibly involve involves some degree of bathing, certainly the more vigorous the bathing, the better the result. And there was some placebo effect, simply suggesting that moisturising the skin can be effective here. .
It's, it's a modest effect. Again, I think anybody expecting, you know, these are not steroids or cyclosporin Aperquil or something, but that can be useful as an adjunct therapy, but they don't last very long. So you're really looking at having to bathe 2 to 3 times a week really to get any consistent effect once a week really isn't going to be enough.
And so this is why the foams and and wipes and so on began to be developed. And the idea was that you could break up the bathing. So this was the old Dxo protocol, which was bathing once a week.
There's the shampoo bottles there. With the, the moose application or the phone application, non non rinsing application in between, because that's a lot easier for the owner. The idea was you'd improve efficacy, prove these for the owner, and maintain, the, the, the improvement.
And the new S3 protocol is this 3-week cycle of, of one shampoo followed by the, the little vet figure there is because these, these diagrams were, were derived from clinical trials. followed by the foam every 2 to 3 days, and, and then if you, if needs be in long term treatment, you could, you could repeat that, that cycle there. And I must admit, when, when I was first involved in some of the discussions over this, I was a little bit sceptical.
And, and at one point I, I did. Unguardedly say, well, that will never work. And, as you'll see later, I, I had to eat my words, somewhat.
So this is looking at a topic dogs, using the code 04, which is the latest version of the validated, lesion scale. And so, under 10 pretty much is a normal, dog, mild, I think that's 35, can't quite remember the top of my head, . mildly affected with AD moderate, and then, and then severe would be, would be somewhere up there.
So these, these animals on average tended to be in the moderate range or the severe end of the, of the mild range. And there was a similar efficacy, using, both the, the traditional protocol and, and then the. The 3 week protocol of one shampoo followed by the mousse, every, 2 to 3 days over that 3 week period there.
And actually in this group of dogs, although there was some variability. Between individuals you can see with the error bars there, there was quite a considerable improvement bringing them back down into the mild to to normal range there, which is, for a shampoo is, is, is quite impressive by itself. And so this is Sorry, I I think I've just been audio bombed by a delivery, the perils of lockdown and we're working for working from home.
So the. The, where was I just lost my train of thought. I start again.
So this is the, the sort of three areas that . OK. Could you just hold on a second, hold on a second, yeah.
Perhaps while we're just waiting for Tim to come back, if people want to just tap in where they're listening in from, that it's always good to see the OK, where everybody's listening from. But back over to you, Tim, was it good, was it good, you can, you can edit that edit that that bit out of the of the record, the recorded version. The perils of live live broadcasting audio bombed by our, by our shopping delivery.
Right, for once they've decided to come early. Right, where was I? So these are the three areas that we're, that we're looking at really.
And so skin bar to, to actually helping the skin barrier itself because we know that this is defective in atopic dermatitis. The skin is just not as good a physical barrier to the outside. This allows exposure of the immune system.
We see allergens and irritants coming in. There's increased transepidermal water loss, and all of these contribute to the dry, irritable, its skin and possibly allergen exposure as well. And then we're increasingly aware that the a healthy microbiome, so in other words, a, a healthy and diverse and rich and even microbiome is really important for skin health.
And what we used to regard as a secondary skin infection, we now know as a dysbiosis where we get this overgrowth effectively of the staphsu intermediate so it takes over the microbiome. And then it becomes much less, diverse and, and even, and that has a strong contributory factor to, to the disease. And then we've got the inflammatory niche pathways as well.
And what, Siva did here was set up. A series of, of, reconstructed human and canine epidermis models to basically demonstrate the effitrium. Which is the, the active ingredient here, which is a product derived from, from Japanese Mondo grass, which confusingly isn't even a grass.
And I'm sure that the video will go through the process of why that was selected much later, but you can see that you're getting much less penetration. So we got a better mechanical skin barrier. It's reducing, the, the over the, the.
Colonisation with the sued intermediate on the stressed models here. And again, we're getting changes or blocking the inflammatory pathways in in the stress stressed models. So it's the first at the bench level range of products that that show impact on these three areas that we're looking to, to improve.
And then this was the, the, the clinical study, again, one weakness here was that this was an open study, so there wasn't a a control group there. So it does need following up with, with, with controlled trials to eliminate a placebo effect. But again, the, the dogs were, were, were the sort of mild to moderate end, of atopic dermatitis, and that's OK because there's very little point taking dogs that are severely affected and trying to, treat them with a shampoo.
It just isn't going to work. You have to be realistic with what your targets are here. But there was quite a considerable, reduction with 13 week cycle, there.
And this was true with the pruritus scores as well, which were, which were, quite significantly reduced with a more than 50% decrease in a little over half of the dogs here, and a high degree of, of satisfaction. OK, so, moving on, the, another way that I, I mentioned was to look at the spot on, preparations. And again, the, these, these are somewhat similar to the spot on flea control products and the idea is they're very simple and easy to use.
And these contain, the, the Alloderm product here contains a variety of basically skin lipid precursors and, and one we know that there are, quite profound derangements or alterations of the ceramide content and balance of different ceramides in a, in atopic skin. And then. There is another range of products, which are, cannabinoids and, and they work through the cannabinoid family of, of receptor pathways.
Don't make you high, so don't, use them for that, but they can reduce inflammation and it and that was shown, in, in vitro and in vivo models as well. Now, fortunately, the Clinical evidence that these are effective is, is much weaker. And there have been a series of abstracts and and papers, looking at this.
And unfortunately, the, the change here was, was pretty modest. That was statistically significant. But there's a question mark about how clinically that significant, significant, particularly with, with little change in the purits and that was similar for the, for the essential oil based spot on here.
Now these products in humans are not really expected to work by themselves and we don't tend to use them as spot ons. But similar things are used as creams or bath oils, and the idea is that you would rehydrate your skin and then put these on. And it did occur to me that these could be more effective used in that way, but I'm not aware of any studies that have shown that.
Now I talked a little bit about the microbial dysbiosis and again, I could, you know, fill half a day with, with this quite easily with, with a huge amount of new knowledge that's occurring with this. The take home messages really are what we refer to as a staphylococcal or malaceia infection really isn't what it is, is a change in the microbiome. That, that we lose this rich, as I say, rich, even and diverse microbiome, and you see this skewing towards a much less diverse microbiome either Staphylococci or malacisia.
So we lose diversity and diversity is key. And it's much better to think about this as a dysbiosis rather than an infection because an infection implies something acquired. That can be treated and got rid of and certainly with Staphylococci here, that's one of the things that fuels repeated courses of antibiotics.
And so if we think about this as a dysbiosis and what we can do to maintain a healthy microbiome and that's becoming an increasingly important part, of treatment. And this, this is a really interesting study from about 3 years ago. And what the what the team did here was took mouse models.
And if you, if you stress the mice, this particular strain of mice by overcrowding them, they actually, you can induce the staylococcal dysbiosis with it. And what they found is you can treat that with an antibiotic either topical or systemic. But what this does is basically suppresses all of the bacteria on the skin.
Including all the nice healthy good bacteria that we want to encourage. And what, what you can get is when you stop the antibiotics is a, is a rebound of the staphylococci before anything else has had a chance to, to go. But with Topo antiseptics, they found that generally.
They lopped the heads off, if you will, these high unstable stress staff populations without affecting the underlying microbiome, so they're much better at balancing the microbiome than by using antibiotics, and I thought that's fascinating. No idea how that works, but it really should encourage us to always think about using topical antiseptics ahead of topical antibiotics. There are lots of studies about topical antiseptics that are beginning to be published because there's lots of interest now in producing new compounds.
But the one certainly that has the best evidence to support its use is chlorhexidine and certainly chlorhexidine products are now regarded as the appropriate first line therapy for surface and superficial. Staphylococcal skin, nearly said infections there, Staphylococcal dysbiosis, in dogs. And again, again, initial, products were generally around shampoos, but to improve efficacy and that's really important in antimicrobial stewardship, there's now a much wider range of, of, of products of formulations available.
Now this is some study that a student did with me back when I was at the University of Liverpool. Just very quickly, these were, we did it with lots of bacteria. This is just a headline table with 3 different MRSP isolates that we had in the lab.
These 3 products all contained chlorhexidine, and these didn't, and you can see that in vitro, we were getting a really quick kill with the chlorhexidine containing products after only 10 minutes up to, quite low dilutions, and for these other products that, that all claimed. So we, we, we selected these shampoos on, on claimed antimicrobial efficacy. The, the, the effect was, was much, much less.
And in fact, certainly at the 10 minute point we saw very little, antimicrobial activity of some of these other products at all. That's just one little bit of evidence there's plenty of other bits and pieces. And certainly one useful impact of property of chlorhexidine is that the, the shampoos, sprays, and other formulations, but not all of them, which we'll come to in a second, do display this residual activity on canine hair.
So basically you can treat a dog and then for up to a week or so afterwards, depending on the product. You can take hair clippings, plate those up with bacteria and show inhibition of bacterial growth. So again, this is helping to prolong the effect post bathing or post application.
Again for topical is very useful. This was the one that was a slight surprise for us. These are the chlorhexidine wipes here.
And we showed that if you took 6 millimetre discs of these wipes, plated them up with lots of different types of bacteria, and we also did some maesthesia, you could show a zone of inhibition, so some degree of in vitro efficacy, at least with standard staff, pseud intermediates, MRSP and E. Coli, which are all about the same. But as soon as we got to the more resistant E.
Coli, we got less efficacy and no, no inhibition at all of pseudomonas there. And this is possibly due to the lower concentration of chlorhexidine in these wipes. So it's, it's 0.15% compared to the shampoos, which are generally 2 to 4%.
There, and just a way of contrast, I've not put the, the, the data on here, because we did compare these two malaitic wipes which are 2% acetic acid, boric acid combination, and we showed no in vitro efficacy at all. We got confluent growth with all our samples on that. So these wipes can be very effective products for people to use, .
But we would say, you know, be careful if you think you've got rods there, if you think that they're pseudomonas, that you may not see quite the same efficacy as with other products. And again, interestingly, no residual activity with these products at all. So certainly if you're treating the infection, you need to use them daily, although for for maintenance, you could use them less often.
So to look now at the S3, yo. So this is a fitrium again, the same as the calm range, but with the 3% chlorhexidine, and this comes as a sort of pads or or wipes there and again, the foam and and the shampoo. And certainly antibacterial efficacy in vitro is, is pretty much the same as the other products there that I showed you in Duoy.
So again, this was using so this, this was the the one where I famously said in a room full of people, all that will never work, when the, when the clinical trial was being proposed. So basically what this was doing was looking at the standard. Protocols.
So that's once a week shampoo with the with the mousse, a couple of times between each, each weekly shampoo. And then the new S3 protocol, which is the 3 week cycle. So one shampoo followed by the mousse every 2 to 3 days.
And this was just a a single 3 week application, so 1 S3 protocol and, and 3 shampoos in this group. And, basically the so it's probably not the best way to do this actually this is a percentage decrease. So the higher you go up here, the, the, the better the outcome.
But essentially there was a reasonably good clinical outcome and there was no statistical difference between the, the, the two protocols and certainly again, the feedback from the owners and the clinicians in this study was very good, suggesting that this, this novel protocol, of these three week cycles of shampoo followed by the mousse AIDS efficacy, sorry, AIDS compliance, which is important in efficacy, which is then important in antimicrobial stewardship because it means that we're not . We see fewer treatment failures, which means that we're then using less antibiotic, which can only be, can, can only be a good thing. So moving off the, off the shampoos now.
And looking at some topical anti-inflammatory products. And again, as I said, the topical products in, in humans are your, are your absolute mainstay baseline of therapy and everything ladders or, or they tend to use models of ladders or building blocks, but everything is worked up from that. And again, the topical glucocorticoids are the first line choice in in, in humans, and they're not always suitable for dogs because we, we, we're dealing with a head species.
But if you think about it, in, in most dogs, and again, perhaps Westie, German Shepherd, sharpe aside, but in most of those other breeds I showed you. It was a relatively focal or local disease and concentrated on the less head areas, meaning that tropical therapy, can be feasible. And the, the really nice thing about glucocorticoids is that they're incredibly broad spectrum and they're very, very quick.
And so I've started using a a, a sort of peacekeeping analogy, for this. If you imagine that you've got a civil war going on with, with, with two, opposing sides fighting it out, and the United Nations comes along and imposes a ceasefire. Now if they can do that, and we'll talk about this a bit later on, at the political level, it is going to take time for those orders to philtre down to the front line, for people to stop fighting and disengage and then the peacekeepers to move in.
But if on the other hand, the United Nations decides to be rather more businesslike about this and sends in, very, very heavily armed peacekeepers with armoured support, air power and and artillery back up, then it is likely that the, the two sides will disengage very, very quickly because there are consequences if they don't. And that's how you can regard glucocorticoids because they just affect everything. So the every cell, involved in the immune reaction plus all the adhesion molecules, mediators, antibodies, and so on and so on.
So this is why you get a very quick, very broad spectrum response. And if I want to do that in an autoimmune disease or severe ectopic dermatitis, I will still go for glucocorticoids because there is nothing else going to do that for me and you get the same effect with, with the topical products. Now with traditional glucocorticoids, using them is certainly a lot safer than using systemic treatment because whilst you are supplying, because the advantages you're supplying the glucocorticoid to where it needs to be, without treating the rest of the body.
So the systemic effects can be much less. But that's not to say that they are. Side effect free and this is the ventral chest of a boxer dog that was treated with a betamethasone product, over about a 3 month period.
And you will see these, side effects and you will see some, systemic absorption, as well. And this is why in humans, you will tend to initially treat with, the more potent products and the, the products are all very carefully, . Ranked in terms of their potency, and then you'll move to a less potent, but safer product for maintenance once you're into that proactive treatment phase.
And there was basically a relationship, the more effective the glucocorticoid, the less safe it was. And then these dyes the glucocorticoids came along as a game changer, because the, the, the tweaking of their structure. So it's this one, this is hydrocortisone ipponate that you'll be familiar with, but prednicarbate, methyl prednisolone acetate, mermetosome are are similar.
These are dye ester products with no halogens. There's no fluorine molecule here. And this basically gives them a potent anti-inflammatory action but ensures their metabolism within the dermis, which makes them a lot safer.
And it's just that sort of relationship I was telling you about. So basically, the more potent the glucocorticoids, this is clobetasol here, betamethasone trimcinolone there. And hydrocortisone here.
So the more potent it is, the, the, the more side effects you have, but the safer it is, the less potent it is. And what these products have done is shifted the graph a little bit because . This is methylprednisolone acetate, which is almost the same as hydrocortisone, acipoate, sorry, predniarbate there memetasone here.
You've got the same anti-inflammatory efficacy as betamethasone and transcinolone, but the same safety as hydrocortisone. And this is the studies that I was involved with years ago now, looking at the Verbank product quartervans. And just very quickly, you know, we showed a very clear benefit in terms of lesion scores, and pruritus with a very substantial reduction.
These were often certainly moderate to severely affected dogs that were being brought down to the, to the mild end of things here. And again, a very substantial and most dogs greater than 50% reduction in pituss compared to placebo. And then this sorry I something's happened there.
But this was a subsequent study that basically showed very comparable efficacy between hydrocortisone ipponate and and systemic cyclosporin, both in terms of lesion scores and purri scores over about a 12 week period. Now this is, just again to re-emphasize the, that concept of proactive treatment, to you. So then, in this study, which was led by, Anna Mafalda Martins in, in Lisbon in Portugal.
And what we did was, basically treated all the dogs with the court of advances to the point of remission and then randomised them to placebo, or, corterants, but just at the weekend. So every Saturday, Sunday, and, and then watched as they fell out. And the median survival time, if you will, before a flare here was about 115 days in the quarter vans group, and in, much, much less in the, in the, placebo group.
And again, these days, I probably would do things slightly differently. Certainly, I think I would treat twice weekly rather than on to, you know, 2 days on 5 days off. And, and, and again, thinking back to that original wheel of, of, of complication that I showed you, we would not normally recommend monotherapy with atopic dermatitis in dogs, whereas these dogs got nothing else, we would be combining this with other things.
Looking at the skin barrier, looking at the microbiome, and possibly even allergens specific immunotherapy. So I think in this proactive, treatment can be very, very safe and combined with other things that can actually keep the dogs lesion free for long periods of time between flares. And we will do this in a topic coitus as well.
So this is off-label use. In terms of the court of ants, but we, again, in a lot of dogs that are that are managed by other means, you can still get flares of otitis and using topical, glucocorticoid there and this, this is true for the conjunctiva and often the feet as well, can be very safe and very effective. Long term, we try there as a topical triamcinolone product now, which is Reicort and long term, my concerns slightly with that are that you potentially could get more absorption and more atrophic change within the skin because remember it, it's a, it's a highly effective and potent glucocorticoid, but long term, it's maybe less safe to use.
In the early stages with chronic inflammation, we can take advantage of that because certainly the problem with chronic inflammation and hydrocortisone sipinate is it may not penetrate deeply enough to be effective. So that's where we can maybe take advantage of the triamcinolone's activity, use it initially once we're back down to normal, we can switch out to the hydrocortisone aipinate for for longer term treatment. But worth remembering that particularly in the ears and and the eyes as well, it's a very, very effective use of these products.
So these are the calcineurin inhibitors. This is basically, cyclosporin groups. So this will be cyclosporin for for systemic use and what I'm talking about here really is tacrolimus on, on the skin that you can use cyclosporin in, in the eyes.
And these have a lag phase. Now, remember my peacekeeping analogy. So this is where the United Nations would go to the two, political centres and negotiate a ceasefire.
And once that's agreed, that then gets communicated to the generals. And then once they agree, the orders fil philtre down to the front line, and the, the, the, the, the the fighting soldiers will cease fire and disengage and all that takes time. And this is because these drugs mainly work on lymphocytes.
Now, every immune reaction. Sooner or later we will burrow down to a lymphocyte, but if you stop those. Everything that's downstream of that will take time and that's why you see this 2 to 3 week lag period before you can start to see an effect or certainly before you see the maximum effect from these drugs.
So if you want something to work immediately, you're much better off using a glucocorticoid. But these are very safe products for long term use, particularly in chronic, inflammatory situations. But just remember that, that lag phase there.
And again, this is something that we use, we use a fair bit in atopic conjunctivitis as well. And my, my experience, I don't know about other people, but my experience here is that atopic conjunctivitis can be. Very significantly debilitating for dogs and does not respond well to systemic therapy as much as topical therapy.
And then just lastly, it's, if you have dogs that are not responding, just, it is worth thinking about other pathways. So, a lot of our, I talked about tonight because I've not really talked about systemic treatment, but obviously we have Lovetmab, yo, and Olaitinib Apaquil. That to a greater or lesser extent work through the IL 31 itch pathway, but we do see animals that don't respond to these drugs that don't respond to these drugs fully.
And this is because they may, they may be working through other pathways and it's worth then thinking about other ways that we can combat that. And, and these are a couple of things there. So again, just to throw that out if you've got these more challenging cases.
And so this is just again to re-emphasize that . This new approach to treatment and where we can build in the the topicals for this. And it's, it's about this reactive treatment to, to, to induce remissions.
This is phase one of our treatment protocol. This has been written up by Terry Oliy Fran Ivanovich, quite recently, just last year. And it's then about thinking about the severity, of the, of, of the disease and the balance between inflammation, and pruritus.
And the more we've got severe change, the more we've got inflammation, the more we need these broad spectrum products, such as the glucocorticoids there because these are going to work very, very quickly, remember? And the more that we're down to mild inflammation and itch, the more we can use the, more narrow spectrum products that are just targeting that. And I guess if you just had itch with almost no inflammation, you could put a local vet map site to point in there as well.
And then same really phase two, we're looking at this proactive treatment, which is to prevent the recurrence. And what we're aiming to do really is as we see the animal move down from the right to the left here, we can move to the, these more narrow spectrum, . approaches, and again, the, the, they, they were emphasising here the importance of proactive topical glucocorticoid, and again in here, I would put in our, our bathing either long term with the calm, or an antimicrobial product and this is where the allergen avoidance and immunotherapy would fit in as well.
My name is Emily, and I'm a best adviser at Animal Health. So in this short presentation, I'll give you an overview of the DUXOS3 range, how the vitrium was selected for DUXOS3, and I'll also show you the final data in some of the clinical studies that Tim touched on in his presentation. I'll start by giving you a brief run through of how Duxwey and its main ingredient came about.
The development of DS3 started with some quite extensive market research where vets and pet owners were asked what was important to them when using a dermatopical. So it's found that pet owners wanted products that are well tolerated by their pets as well as themselves, because they are the ones to apply the product, and they also wanted products that don't contain any controversial ingredients. What was also important to them was that the product obviously had proven performance on the skin barrier, and this was also the key factor for vets.
And these results then provided the criteria for the search of the active ingredient fords of vey. So with the market research done and the criteria identified, that they could then then get on with the selection process for the active ingredients. And this started off as literature searches where more than 250 ingredients were identified.
These ingredients were then narrowed down to more more than 50, which went through an in-depth research and development analysis. This identified two high performing ingredients which were subsequently tested on human and canine skin models. And following these in vitro tests, fitrium came out on top with beneficial effects on the three skin barriers of the mechanical, microbiological, and immunological skin barriers.
And beytrium is a natural extract from the Japanese monograss plant or Oopagon Japonius. We'll now move on to some of the field trials that have been carried out for DUXO S3, and I'll start with DUXO S3 PIO. So Dixo S3O contains eytrium and 3% chlorhexxale diluconate.
And this trial, the objective was to assess if weekly shampooing with mousse applications in between was a key factor when managing bacterial or yeast overgrowth cases, or if one initial shampoo at the start, followed by mousse applications for 3 weeks was sufficient. So the dogs were recruited to this study. They were clients on dogs that had a bacterial and or yeast overgrowth that was diagnosed by dermatologist.
The overgrowth was diagnosed by cytological examination and the severity and extent of the lesions were also given a score to make up the bacterial overgrowth score. The dogs were then allocated to one or two protocols, so they were either given one shampoo at the start, which was followed up by mousse applications every 2 to 3 days for 3 weeks, or they were given weekly shampoos, followed by 2 mousse applications, 2 to 3 days apart for 3 weeks in between the shampoos. And the dogs were assessed by a dermatologist on day 0, day 7, and day 21.
Moving on to the results then, so as you can see from the graph, there was no statistically significant difference between the two protocols. So this shows that one shampoo followed by mousse applications is as effective as shampooing once a week and having mousses done in between the shampoos. And as we all probably know, dogs and especially cats don't always like to be bathed.
So the fact that the owner only has to give. The pet bath that one time at the beginning, and then just use a leave on moose, could really improve compliance as it makes it a lot easier and more convenient for the owner. The pets also gets a really nice massage during the application of the moose, which makes it quite nice and enjoyable for them as well.
And obviously chlorhexidine, which is in the ducts of S3 pio range, we do know that that can be quite drying. We probably all know that from scrubbing up to several surgeries a day, we get quite, quite dry and crackly, itchy hands. So the added a fitrium to the range actually helps to counteract that drying effect, which makes the skin quite nice and hydrated.
There's also a nice added hypoallergenic cocoa vanilla scent, which masks the smell of the chlorhexidine, because chlorhexidine can have quite a medicated smell that owners don't usually like. So the addition of this scent actually could also help with compliance as the pets will smell nice and fresh, throughout the day instead of smelling like steam. Here is an example of one of the cases I was part of this trial.
And this is an 8 year old French bulldog that has suffered from itchy skin and optitis from the age of 8 months old, so quite a long time. He had been diagnosed with allergies, but kept having frequently relapses of bacterial overgrowth, which is quite frustrating for the owner, really. So as you can see in the image on the left, the dog had a large epidermal coloret on his abdomen.
The pink line there is from, is the remnants from a previous unsuccessful treatment attempt. But this dog was started on DixoS3 yo, where they used one shampoo at the start of the protocol, and then followed by mousse applications every 2 to 3 days for 3 weeks. And after 21 days, you can see that the lesions have have healed and cytology was was negative for any bacteria at that point as well.
In this next study, we're looking at the use of pile pads for localised lesions, bacterial and or yeast overgrowth in dogs. So the dogs included in this study were diagnosed with focal bacterial and or yeast overgrowth lesions. And that was done by cytological examination by a dermatologist.
So and they also scored the severity and extent of the lesions. And the owner's perception of of how itchy the lesions actually were at the time. The pads, pile pads were used once daily for 14 days, and the dog's cytological and itch scores were evaluated by a dermatologist and the owner on day 0, day 7, and day 14.
Moving on to the results then. So as you can see in the graph, the mean bacterial and yeast counts significantly decreased after just 7 days of daily applications of the pads, and 89% of the dogs in the study had cytologically recovered after just 14 days of of applying the pads to the affected areas. And this showed that the Dixo esto yo pads were effective at disinfecting the skin and restoring the skin's microflora.
When looking at the itch scores, there was a mean decrease of just over 71% at day 14 when compared to day 0, which shows the soothing effects the pads have on the skin alongside its antibacterial and. Properties. So this is important as the itching is what the owners see and by seeing an improvement in the scratching and licking, they will they will probably be more likely to continue using the product till the end of the protocol.
And 94% of owners were also very pleased with how effective the protocol was. If you would like to read further about this study, this has recently been published in Frontiers in Veterinary Medicine, and it's available as open access, and you have the reference at the in the bottom right corner there. So this is a little Yorkie that was part of this trial and she presented to the vet with a very itchy and crusty lesion on the bridge of her nose, and the cytology revealed a yeast overgrowth and she was started on DOS3 pile pads.
And after just 7 days of using the pads, the owner reported that the itch had completely resolved, and after 14 days of daily pad use, the yeast overgrowth had completely cleared up and the use of the pads was stopped. The dog was then seen again two weeks later, but for another concern that the owner had at the time, and you can see from the image on the on the far right there that the skin has fully healed without any recurrence of the problem. Next, we'll have a look at the European field trial for DuxoS3 calm.
The objective for this study was to evaluate the performance of DoxoS3 calm shampoo and mousse in dogs with sensitive skin that presented with a skin flare-up. So for dogs to be included in the study, they had to be up to date with their parasite control and have no other skin conditions, such as a yoderma. The dermatologists assessed the dog's CADC scores on day 0, day 7, and day 21, and the owners assessed their dog's score at the same time points.
The protocol that was used in this study included one shampoo at the beginning, followed by mousse applications every 2 to 3 days for 3 weeks. So looking at the results, at inclusion, the mean CAD score was 18, and by day seven, the score had decreased to 7.9, and this continued to decrease to 6.4 by day 21.
A score below 10 is considered to be normal. So this showed a mean decrease of the CADI score of 58.3% at day 21 compared to day 0, and almost 70.4% of the dogs had a decrease of 50% or more in the CAISE scores at day 21 and close to 80% of the dogs had a score of less than 10% at day 21.
When they're looking at the itch scores, there was a mean decrease of close to 31% between day 0 and day 21, and the reduction in the scores at day 7 and day 21 were statistically significant when compared to day 0. So this shows that DixoS3 calm when you're using one shampoo, followed by mousse applications every 2 to 3 days for 3 weeks, has soothing effects on the skin and significantly reduces itching. To show you an example from this study then, here we have a one year old Staffy type dog with red, irritated and very itchy skin.
And excoriations in his a silly. He was suspected to be a topic, but he was on no immunomodulatory medication at the time. So he was started on Dus S3 calm shampoo and mousse, where they gave one initial shampoo, followed by mousse applications every 2 to 3 days or 3 weeks.
And after 21 days, you can see that the redness and excoriations have gone. And the dog was much more comfortable and he wasn't scratching anymore. Lastly, I'll give you an overview of the Dux of S3 family and the 4 ranges that it comes in.
These are the four ranges of Duxo S3 that we have. So you have your calm, yo, Seb, and care. So Duxo S3 Calm is for dogs and cats with itchy, irritated and sensitive skin, and calm has a higher concentration of vitrium in it compared to the other ranges, and that's to provide that extra soothing effects.
And this is available as a shampoo and a mousse. DixoS3 pyo contains eytrium and 3% chlorhexidine diggluconate for those cases where you need an antibacterial or antifungal action. The added fitrium to this range helps to counteract the drying effects of the chlorhexidine, and it also supports the skin barrier, and this is available as a shampoo mousse or pads.
So for your oily or dandruff your patients, you have the Dexa SVE range and the se contains aytrium and seals. Seances is a natural extract from the pomegranate peel, which helps to normalise the keratinization process, and you have this available as shampoo and a mousse. And lastly, there's a Duxo Sweet care range, which is, which is your general shampoo that can be used on any dog or cat, if you like, as well as puppies.
And this, this also contains a vitrium to support and protect the skin barrier and you have that available as a shampoo. Thank you for listening. If you have any questions or would like any further information, you can always email me on the email address on this slide.
On the webinar page, you should also have access to a dynamic PDF called Journey So Far, where you can access all of our brochures, recommended protocols, case studies, abstracts of studies, and more. So please head there for for more information as well. Thanks again.
Thanks again.
