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Psoriasis showing on elbow

Roundtable discussion: Biologics in plaque psoriasis

Transcript: Switching and combination therapies to optimise response
Last updated: 24th Apr 2024
Published:24th Apr 2024

Professor Luis Puig, Professor Matteo Megna and Professor Matthias Augustin

Roundtable recorded Apr 2024. All transcripts are created from roundable footage and directly reflect the content of the roundtable at the time. The content is that of the speakers and is not adjusted by Medthority.

And I would like to start by showing you a graph which comes from, there are many publications like those, with those Sankey graphs, in which you can see the itinerary of patients, because we used to see our patients getting complete clearance quite often and follow on that, but that's not the practise for most of the patients, especially because they have started for a long time ago, perhaps with some drugs which might be inferior, taking into account current standards, in terms of efficacy, in terms of safety, in terms of durability of the effect. And then eventually, these patients, the degree of satisfaction, or let's say confirmation in terms of effectiveness has changed.

Nowadays we are more exacting in terms of the degree of response that they want to achieve. So this has also led to changes in treatment when newer drugs, more effective drugs appear. And since we are compelled nowadays in many countries to start with biosimilars, again, the promise of immunogenicity with adalimumab come back as a matter of concern. We are seeing loss of response, perhaps in up to 40% of patients or even more. Anti-drug antibodies appear in the course of treatment relatively early on. And this might lead to loss of response, even in the case of infliximab of course, in infusion reactions and the like. And there's been one proposal that was to add methotrexate to this combination to improve the durability of the response.

This has been proved to be true for rheumatoid arthritis patients in rheumatology, but it has never been proved to be really effective, especially for patients with psoriasis. Because we might prevent a bit, the appearance of anti-drug antibodies, but eventually, methotrexate, especially also in our patient population with the whole liver disease and the like, is able to increase the gastrointestinal adverse events, and eventually those patients must be switched because of that. So, that's a bit of a problem with a combination of methotrexate with adalimumab. We are not using that anymore in most cases. Then we have combination with UVB. This among many cases is unpractical. And topicals. The idea of biologics is to be able to get rid of topicals. So in the end, topicals are just for some refractory lesions. I would say refractory areas are not special areas. Difficult to treat areas are perhaps the legs, the sacroiliac, the forearms.

These might be more difficult, and then the use of combination with some topicals might be very helpful. There's another issue about the dose escalation. In the real world it is often required for patients underweight, and quite often we are using high doses, especially when there's a flat price of ustekinumab a bit off label for patients weighing less than 100, but still in some other cases the adjustment are, the possibility of adjustments are included in the summary of poly-characteristics. and the frequency with which we need to do that might also depend on the drop. But again, any increase in dosing might increase the cost and reduce the efficiency of treatment. We know that with second line biologics, the persistence is always lower than with the first one. And we know that the greater the number of biologics a patient has been through, the lower the persistence and generally when a patient has failed a TNF-alpha antagonist, this is not effective as a second line, not in psoriatic arthritis not in rheumatology, so it's better to change the class and to switch to something else.

Nowadays, in most cases, unless the patient has psoriatic arthritis, if it were not because of efficiency, we would not be starting with anti TNF-alpha agents in most cases nowadays. And then the real-world switch patterns change over time, and in some cases, some patients might stop treatment on demand perhaps, because of they want holidays, they want cyclic. We are getting back perhaps, in some cases, to cyclic treatment schedules, not because of safety concerns, but also in sometimes, because in the United States the patients are losing their insurance or in some other, in some parts, the patients might be moving or perhaps purely because of this success, and management of success nowadays is more important perhaps than management of failure, which was our main concern not so many years ago. And that ends my comment and perhaps you will be willing to give your view on these topics.

If I may start looking at the real-world situation then, we see in the registry, which, in the meantime, has accumulated a large number of patients, that the switches do not happen at an early time point, and also not in a obviously not sufficient treatment situation. Many patients stay on the drug even if it's, they barely reach PASI 75. So I think in the real-world, many derms think conservatively and want to keep the patient on the drug in spite of many drugs available. I don't know if this is also your experience, but the potential for treatment optimisation is there, and in some, I think I would switch before. And of course the question is, do we really lose probability of response with the switching itself, or is it another selection effect?

I don't think it's the switch per se, but it's a selection of those, who after several switches Yeah. come out to be really hard to treat patients. Yeah. I would like to add that PASI 75, or relative improvement, is not the way to assess the response of patients, because in most cases, we are not starting our patients on a PASI of 20 like in clinical trials. So most of our patients will start with a PASI of 10, 12, which is really severe. Psoriasis patients are quite miserable with that. So, eventually our goal is to keep our patients on a PASI below 2 or with some limited body surface area minimal disease activity. Matteo, what's your take? Yeah, yes, I agree. Also we, in clinical practise, do not look at PASI 75, PASI 90, but to residual PASI in failure to 2 or 3, so minimal disease activity.

Yes. So, this is the main outcomes. And so thanks to our interleukin drugs, we are using very, very infrequently the association between conventional systemic DMARDs and the biologic drugs. And of course, all this reinforce the importance to try to choose the most efficacious drugs since the beginning to keep the long-term control of the disease. And so we all know that with all class of biologic drugs, when you use the drugs as second, third, fourth choice, that the efficacy cannot be the same as for biologic patients in clinical practise. In my view, when we analyse drug survival curves, only real switching is the real hallmark of failure. Because in some patients, some cases, patients might be willing to stop treatment for many reasons, surgical intervention, pregnancy, Yeah. holidays, whatever, and the way in which we interpret the the data from real-world evidence, or series, or registries, might differ a lot, depending on which is the kinds or reasons for discontinuation we are censuring or not.

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