Psoriasis: an update on topical and systemic therapies

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Psoriasis is a chronic immune-mediated disease which can affect both physical and mental health. In this episode with dermatologist, Dr Jonathan Chan, we will discuss the different types of psoriasis, how it's diagnosed, and the treatment options available.

Hi, and welcome to the Australian Prescriber Podcast. I'm Jo Cheah, hospital pharmacist in Melbourne, and your host for this episode. It's a pleasure to welcome Dr Jonathan Chan.

Hi, Jo.

Thank you for joining us. Dr Jonathan Chan is a dermatologist at Sir Charles Gairdner Hospital and clinical associate professor at the University of West Australia in Perth. So, Jonathan, to start, I thought it would be good to have a quick introduction or refresher. So what are the causes of psoriasis?

It's a difficult question to answer mainly because it's so genetically linked. I think it's probably more important to actually talk about what psoriasis as an entity is and how it's actually evolved over a period of time. So psoriasis is predominantly a skin disease and it presents with well circumscribed red, salmon-pink plaques with very non-adherent scale. So it's a scaly red skin disease.

It usually occurs on external surfaces, so things like knees and elbows, but it can occur all over the body. That's how it looks like. But to actually talk about the entity of psoriasis, I think, it's really important to get back to what it is. And as you said in the introduction, it's an immune mediated systemic disease, and it is systemic. And I think as soon as somebody has any plaques at all in their skin, they usually have inflammation somewhere else. And that somewhere else includes their gut, their joint. It can be inflammation around their eyes.

And so it's really a disease which is whole body but predominantly presents as a rash. And when you talk about psoriasis as a rash, there's many presentations. That's why we originally talked about what types of psoriasis. There's guttate psoriasis, [where] there's like little raindrops all over the body, and then there's standard plaque psoriasis. So plaque is probably 5 to 10 centimetres in diameter in areas which are traumatised, elbows, knees, that sort of area.

But it can go all the way to where people have extensive disease, whole body. So they're all red. Erythrodermic psoriasis, they can be limited just palms and soles. And so it's this disease where there's multiple presentations, but essentially when one sees a person with psoriasis, one has to recognise that it's more than just skin deep.

Definitely. So at what point do you think patients should be referred to a specialist if they were originally being seen by GP or even in a community pharmacy?

I think if a disease is not gotten on top of. So if there's a rash, and the only treatments are topical therapies. If they tend not to settle down with it, I think it is really time to push on. I think it's really important now to talk about what psoriasis actually is in terms of its impact for a patient. It's a disease which has significant quality of life impact.

We could give an example of an 18-year-old young lady, has a sore throat that's associated with guttate psoriasis. She comes up with guttate psoriasis. She's spotted in the face, the trunk. Suddenly she's got this rash. She's embarrassed about what it is. She's worried that it's contagious. She feels worried about this. Will it impact her? Will it impact her job chances? Will it impact the way in which she makes friends?

So the impact of just a bit of skin disease is actually a lot more than what might be clinically obvious. Coming back to your question, when should a patient be referred? I think if the rash fails to settle and the patient comes back to the doctor or back to the pharmacist, it really means that it's more of an impact than just what one can see and it probably needs to go on and see a specialist.

We have access to some great medications now which can essentially clear psoriasis, almost a hundred percent clearance of skin. And that's the expectation we have once we start a patient on treatment.

On the topic of the quality of life impacts that psoriasis can have, what other holistic treatments or supports can you offer a patient if in addition to treating the skin condition, if they are feeling that it's impacting their quality of life?

Yeah. It's difficult mainly because it is so hard to get rid of without the specific therapies. For us, it's easy because there's a treatment that works and once you start them on a biologic for example, they're clear. But up until that point, really nothing much works that well. Diets may have an impact on some people, particularly alcohol, but really there's lots of psoriasis diets out there. They have a modest impact on psoriasis, on patients.

Similarly exercising, getting a bit of sunlight, sleeping well, stopping smoking. They're all good things to have, but they have a marginal impact if any, on a patient with psoriasis. Every so often you'll have patients who say, ‘Well, when I stopped drinking milk, my psoriasis settled.’ But they're never ever clear and I think it's more that some diets are just more pro-inflammatory for some patients than others.

So in terms of holistically, it's good to exercise. It's good not to eat junk. It's good not to drink too much alcohol. It's good to stop smoking. I mean, they're all great for health, but unfortunately they don't do a huge amount to improve somebody's psoriasis.

And since we've been talking about some treatments already, would you be happy to discuss the various topical and systemic therapies for psoriasis?

Absolutely. The mainstay of treatment in the community, I suppose would be the creams. So there's calcipotriol cream, which is the type of vitamin D analogue that works well. It's now only available in Australia [on the PBS] mixed in with a topical steroid. The mainstay of treatment really are topical steroids, but it's a 2-edged sword because psoriasis is exquisitely sensitive to topical steroids in terms of tachyphylaxis [reduced response over time]. And so often you keep on applying topical steroids and suddenly it stops working and it comes back even worse. So topical steroids are really not a great long-term therapy for it. Before the advent of things like topical steroids and calcipotriol, people use things like tars and salicylics [salicylic acid]. So they're keratolytic. They're messy, they're smelly. They do settle the scale down, but they don't actually clear the disease.

Similarly, old therapies like Dithranol (an anthralin); it's an anti-metabolide, it slows down skin growth. It stains the skin, it's smelly, it can burn. All of the topical therapies, there's a limit to how far we can use with it. Certainly if somebody's really scaly, you even put just a simple emollient on it like a simple moisturiser like QV cream or something and it looks the scaly. So that helps the appearance, but it doesn't really turn off the inflammation or really take the disease away that active therapies can do.

So where would we go in addition to or after trying the topical therapies?

So psoriasis is quite sensitive to UV [light], especially UVB. And so I suppose we're now talking about some of the treatment options that are available for a specialist or advanced GPs. GPs have a special interest in psoriasis. So we have access to narrow-band UVB. So it's a particular waveform of light which really turns off the inflammation and slows down the growth of psoriasis. I suppose it's a good time now to actually talk about the pathology, a little bit of psoriasis.

So what happens with psoriasis is that the immune system is turned on, and there are many causes of why it turns on. But the end result of that is that the skin cells rapidly proliferate. So instead of taking about a month for a non-specific cell to actually grow and become an invisible scale going basically from the bottom of the skin to the top of skin and coming off, sometimes it cycles within a week.

And because it grows so fast, the skin cell doesn't lose the cell organelles within. It doesn't differentiate properly. And so you then can see the scale. And because the skin grows so fast, it thickens up very quickly and that's where you get the pathological term acanthosis, thickening of the skin. So when you talk about the treatments of psoriasis, you can reduce the scale. So that's like moisturiser. You can try and slow down that hyperproliferation. So that's where things like the calcipotriol [cream] comes in, the tars come in, the topical steroids come in.

You can try and turn off the inflammation, which is where the topical steroids work. When you talk about systemic therapies, UV tends to slow down the hyperproliferation and it helps settle down the inflammation. If you talk about things like [oral] methotrexate, that slows down the hyperproliferation of those keratinocytes and does have some impact in terms of the inflammation. So really they're the mainstay of easy-to-access treatments. There are a whole bunch of new medications. There's a drug called apremilast, which is a PDE4 inhibitor that works more towards a prostaglandin pathway. It's modest in its effect on the skin, but pretty good for joints.

There's another drug called deucravacitinib, which is a TYK2 [tyrosine kinase 2 inhibitor] inhibitor, and that works in a slightly different way. It works on cell signalling, which reduces one of the interleukins which drives psoriasis. So as time is going on, we're getting more and more novel treatments for psoriasis, but the end result, it's to really stop that immune-generated hyperproliferation of keratinocytes in the skin.

And would you recommend particular treatments if a patient had particular comorbidities? So for example, psoriatic arthritis or any other various type of psoriasis?

Absolutely. I think the thing is, as we said before, if there's good-going psoriasis, there's a high chance that there's already some of these other comorbidities going on, even if they're undetectable. When somebody starts getting things like psoriatic arthritis, the danger is that if there's damage to the joint, it's irreversible. And so really once a patient starts getting the typical joint type symptoms of psoriasis, then I think they really need to go on and see a specialist and get some form of systemic therapy.

If they've got any comorbidities like psoriatic arthritis or if they have blood in their stools, I mean, that's obviously an indicator that they may have more an inflammatory bowel disease. So any of these comorbidities, I think they really need to move on and get some form of systemic treatment.

And would those systemic treatments be managed by, for example, the rheumatologist or the gastroenterologist or in collaboration with the dermatologist?

Generally in collaboration, I think one of the quirks of psoriasis, psoriatic arthritis, is that a dermatologist can get onto a biologic [medicine] a little bit easier than a rheumatologist may be able to get on with psoriatic arthritis. There's no blood test for psoriatic arthritis, so it's a clinical diagnosis. And to get onto a biologic, so now we're talking about medications, we can actually change the course of the disease. We have some strict criteria, but there's even stricter criteria for a rheumatologist. And so in some ways it's easier for a dermatologist to get onto treatment quicker.

On saying that, I see a lot of patients, we do screen them for psoriatic arthritis. If it's relatively simple, we would just crack on and get them onto a biologic, which tends to work in both fields. But if it's a little bit tricky, sometimes not sure whether those cases are osteoarthritis or psoriatic arthritis or a combination of both, then I have some good colleagues who fast-track seeing my patients and then I get them seen by a rheumatologist.

In talking about biologic medicines, you were saying that they can change the course of the disease. So, are there any risks or monitoring that we would need to do if you did start a patient on biologic medicines?

To get a patient onto a biologic in Australia for skin disease, we need to fail 2 conventional type therapies. So going back to some of the systemic options available, there is narrow-band UVB as we talked about. There's acitretin which is a type of vitamin A. It's a retinoid that has some impact in terms of changing the differentiation and growth of skin. We have cyclosporin, which is predominantly an anti-T cell medication, and that turns off the inflammation which reduces the psoriasis.

And then we have methotrexate. So to get onto biologic, patients need to fail at least 2 out of all of these treatments and they need to trial for at least 6 weeks. And so, if a patient is being tried for methotrexate and has failed that, and then started on cyclosporine and they've failed that in terms of their skin has not improved enough, then they qualify for having a biologic in Australia.

And there are essentially 2 families, 3 families of biologics, but really 2 that we use a lot of. One is a type of anti-interleukin-23, which is sort of a controller interleukin and the other is [anti-]interleukin-17, which is more an effector type of interleukin. And so both of these are incredibly effective at healing the skin, getting it close to a hundred percent clear. And because they get things clear, they also seem to have big impact on turning off inflammation systemically. So there's some data coming out now that if a patient starts off with just skin disease and they started on an [anti-]interleukin-23 for example, then they tend not to progress on to get psoriatic arthritis in 5- or 10-years’ time.

So it does seem to have an impact in terms of progression of the disease and maybe changing the course of the disease. Now, once you actually clear somebody's skin, it significantly impacts the chronic life-course impairment. So chronic life-course impairment is a measure of how much impact the disease has, in many ways. So it's not just the disease, but its impact on quality-of-life life choices that somebody gets just because they've got skin disease, as well as some of those other comorbidities that some people can get. And so strong data out there showing that there's a complete change in the CLCI [Cumulative Life Course Impairment] for a patient who wants to start on a biologic.

And would they be on the biologic long term?

Yeah, a really good question. I think because psoriasis is a genetic disease, I don't think we can change the way the immune system is triggered and causes psoriasis. There are some great studies out there at the moment where they aggressively treat early-onset disease. Now, there's a paper talking about a group of patients who have first onset of guttate psoriasis, and they're really given megadoses of an [anti-]interleukin-23. I think the data is now up to 90 weeks. There's still no evidence of any psoriasis whatsoever and a blood test looking for a circulating and inflammatory marker is gone.

So it seems to be that that can at least delay the onset of disease. There's also some really nice data showing [treatment at] early onset. In this case, they looked at less than 2 years onset of psoriasis, [patients] were treated quite aggressively with an [anti-]interleukin-23. They tended to go into remission. In other words, they tended to use much less biologics and they had better quality of life and skin outcomes now up to 4 years down the track.

So I think early aggressive treatment disease seems to indicate that that will give a better outcome overall for a patient.

And what side effects or risks are there with starting a biologic in this condition?

So the [anti-]interleukin-23s are actually incredibly safe, and we don't usually expect to see any side effects at all, which is really quite unusual, isn't it, when you've got a drug which has such great impact on disease that has almost no side effects. Now, [anti-]interleukin-23s are also used in inflammatory bowel disease and in some cases they use 10 times the dose of what we use in psoriasis. And so the safety profile of those drugs that are really quite impressive in that we don't usually expect any side effects whatsoever. The [anti-]interleukin-17s, being an effector interleukin, is associated with a little bit more side effects.

The stronger [anti-]interleukin-17s are associated with increased risk of thrush because that is actually one of the interleukins that's used in terms of generating an immune response against things like candida and so on. So we are starting to see some patients, especially when you start the course of treatment where they have a loading dose. They have an increased risk of having things like oral thrush.

So if you actually look at these 2 big families of drugs that we tend to use for psoriasis, they're actually incredibly safe overall and really not with many side effects that we would expect. Certainly none that would stop us from continuing the medication.

And are there any other clinical trials that you're excited about in this particular area at the moment, or are we still just gathering data from the newer biologic therapies that we've discussed earlier?

We've had biologics for psoriasis now for 25 years, so we are really quite established in that field. I think a lot of it is just refinement of what we have. So, we have the 2 main families, the [anti-]interleukin-23s and [anti-]interleukin-17s. We have now started to look at the more difficult to treat psoriasis. So palmar plantar psoriasis has always been difficult. There's some subsets of psoriasis. There's a very rare but quite devastating pustular psoriasis where the whole body just explodes in pus.

So there are some treatments now available for that looking at different interleukins. So there's an [anti-]interleukin-36 or spesolimab. So there's more research going into the refinement of general psoriasis, I think partly because our treatments are really good. So one of the ways in which we originally looked at whether a drug worked is we looked at something called a PASI 75. So PASI is a psoriasis activity severity index, is sort of an objective measure of it.

And a PASI 75 means a 75% improvement in that. And now we're getting drugs where the PASI 75 is too high. In other words, we're now looking at PASI 100 drugs that give us a hundred percent clearance. And some of the medication we have available, like 70% of patients will have a PASI 100. So when we are starting to get to such effective drugs, it's really now refinement, I think at the edges. The next big thing I think will be oral medications. I'm not so sure about the efficacy of those because all of the biologics, of course, are injection drugs.

You have to inject yourself, so to speak. But some of them are just 4 times a year, which means you only ever think of your disease 4 times a year because your skin is completely clear. Whereas oral medication, you have to take it every day, which implies that you're not really ever clear of disease. You've just got to keep taking it. But I'm saying that that's going to be great for children, for example, where it's always difficult to give injections.

And so oral biologic type medications are coming with decent PASI 75 efficacy. So I think people are more refining now rather than looking at the great big breakthroughs because I think in many ways psoriasis has been licked.

So given how effective the treatments are in the area and how much they can improve the disease and the quality of life, it seems that referral as soon as possible is really important so that patients can get on top of their condition?

So I am biased because when I look at a patient with psoriasis, I know how much of an impact this potentially can have. And because we have these great medications available, it almost implies that these patients need to all be on them. And this is of course difficult because these drugs are seriously expensive. And also getting into see a dermatologist is difficult. I started a psoriasis clinic as an urgent case, so if a GP had a case of psoriasis, they could get them in urgently, and now we're blowing out to 6 or 7 months for a patient to come in because we're just so busy. So access to treatment is still going to be difficult.

Yes.

Basically, if a patient has got moderate to severe psoriasis, I think it's better for them overall in terms of the health that they get onto a biologic. There's also some data to show that patients with untreated psoriasis have a 2 to 3 times increased risk of heart attacks and strokes. They have a 3 times increased risk of diabetes. There is this odd association with metabolic syndrome, and it's really chicken or egg, is it that people with metabolic syndrome have high risk of psoriasis. These are all things which are yet to be teased out. But overall, once a patient is started on a biologic, it appears that all of those other non-specific comorbidities, seem to improve as well.

It almost points to the fact that if a patient has got significant psoriasis, it's actually better for their life and health overall if they can get on to a dermatologist with an interest in psoriasis and get onto a biologic as soon as they can.

For our listeners who might be visual learners and might want to look at some photos of the different kinds of psoriasis that they might come across, would you recommend any references or websites that they can refer to in their practise?

Yeah, so DermNet is a fantastic resource for dermatological diseases, which is run through the New Zealand Dermatology Association. We've got one in Australia, but it's nowhere near as comprehensive and complete as DermNet is. There's also many support groups for psoriasis on the net. It's a matter of just searching psoriasis support groups, and there's usually a lot of pictures, a lot of information available.

Yeah. Well, it's been great to talk to you, Jonathan. Thanks for your time on the Australian Prescriber Podcast.

Thanks so much for having us.

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Jonathan's full article titled Psoriasis: an update on topical and systemic therapies is available on the Australian Prescriber website. The views of the host and guest on the podcast are their own and may not represent Australian prescriber or Therapeutic Guidelines. Jonathan Chan has received speaker fees or conference registration fees from Johnson & Johnson, Janssen, AbbVie, Novartis, La Roche-Posay, Sanofi, and UCB Pharma, and has been on advisory boards for AbbVie, Bristol-Myers Squibb, Janssen, and Novartis. I'm Jo Cheah, and thanks again for joining us on the Australian Prescriber Podcast.