The Institute for Continuing Healthcare Education

Therapeutic Hotline_2023_UCBIL17

MD, FRCPC

Explain the role of the IL-17 pathway in the pathophysiology of chronic inflammatory dermatologic disorders

Review data for IL-17 inhibitors for the management of inflammatory dermatologic disorders

Discuss strategies to educate patients about IL-17 inhibitors and incorporate these agents into clinical care

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Psoriasis

On-Demand CME Videos

Therapeutic Hotline: Expert Perspectives on IL17 Inhibitors in Targeted Management of Inflammatory Skin Disorders

IL Inhibitors

Hi, I'm Mark Lebwall, and I am pleased to be giving this talk on the therapeutic hotline on IL 17 inhibitors. This session is supported by an educational grant from UCB. I am the dean for clinical therapeutics at Mount Sinai in New York City, have been chairman of the Department of Dermatology for the 25 years before that, and I'm very pleased to be doing this talk with my friend Ron vendor. Ron, please introduce yourself. I am Ron vendor from Canada. I am part of McMaster University here in Hamilton, the home of evidence based medicine. And this program is approved for one quarter point 25 AMA CME credits. So, Ron, let's start out and tell us what's new in IL 17 inhibition. What are the new developments? Well, we've had three very stable anti IL 17s on the market for quite some time, sachicinumab, ixicizumab, and brodalumab. And the newest, antiil 17 is vimicizumab. That was approved about 18 months ago in Canada and Australia around the same time, February of 2022. And this is a different anti il 17. It affects the a and AF as well as the f part. And this allows a different type of efficacy, as well as an extended type of frequency in terms of injection. So instead of the usual frequent every two to four week injection of the other anti Il seventeen s, the mechizumab allows every four to every eight weeks. Yeah. Interesting. We've always known il 17 a is important because secuchinumab works so well and ixicizumab works so well, and 17 a clearly plays a major role. But it turns out 17 f is more prevalent in the skin of psoriatics, and that may explain why blocking the two together gives an added benefit. One of the things that we know about il 17 blockade is that these are the fastest drugs we have, and we've actually published data on this, where the three fastest drugs, until bimikizumab came out, were indeed bridalumab, ixicizumab, and sechiniumab, in that order, very fast, all three of them. And now, of course, we have this data on bimicizumab, which shows that at week four, over 75% achieved passy 75. So a very fast therapeutic outcome. What about the degree of efficacy, Ron? Well, at the Pasi 100, which is our target that we're trying to get to all the time, by week 16, we're seeing the majority of patients, almost 60%, are Pazi 100. Now, when we have the ixicizumab and psychicinumab and verdeliumab. And we look at them all at four weeks. It's hard to clinically tell the difference at that point. But by week 16, when you're having 58% with bimikizumab that are Pazi 100, that's extremely impressive. Ron, now that you have experience with bimikizumab in the real world, what can you tell us about the fungal infections which we know were reported in the clinical trials? Well, the good news is that my real world evidence that I'm seeing in my practice is mimicking what was reported in the clinical trials where the fungal infections that I see with bimikizumab is oral candidiasis. That's very easily manageable, does not recur often whatsoever. Most of the patients have one or two episodes, responds to either oral nystatin or oral diflucan, which is available by prescription here in Canada. And the patients are doing so well with it that they really don't want to stop the mcKizumab because of one or two yeast infections. And we're not seeing extensive yeast infections. No one had to stop it in my practice, because of oral thrush. It occurs less than 25% of the time in the first four months, and then when the dose is extended to every eight weeks, we see it half of that. So maybe 9% of the time, and that's maybe where they're getting their second episode. Yeah, you show a picture also of tinia versicolor, which I'm glad you're showing. It was not reported in the clinical trials, but we also have seen with other IL 17 blockers. Tinia corporus developed when I, years ago, took care of a patient with chronic mucocutaneous candiditis, which is an IL 17 deficiency. That patient had horrific tinia infections. But in the clinical trial, what we saw really was limited to infrequent, mild to moderate monilial infections that were easy to treat. And as you see here, that in the first year, 9% of patients had one episode, another 4.1% had two episodes, and almost nobody had more than that in that year. Over two years, those numbers hardly changed. A small fraction of a percent more had one or two episodes during the two years, and very few patients had more than two episodes. So, infrequent, mild or moderate, and easy to treat. Agreed. So my next question to you is, how, why, and when do you switch from one biologic to another if the patients are doing well? I'm not switching anything, even if they say, oh, I'd like to have something that's less frequent, leave well enough alone. Very rare nowadays to have a primary non response. This lack of initial efficacy, we just don't see that with the power of these biologics anymore. The secondary non response, again, is very uncommon. It may occur 1015 percent of the time. And we know that the more biologics that we use to treat these patients, the tougher it is and the more secondary response. Of course, if there's an adverse event, we're going to switch the biologic, and occasionally the patient is not that satisfied. So we may do a switch, but generally, if they're doing well, we don't do a switch. If they're not doing well, we'll switch. Now, if they had secondary response, I will switch within class. If they had an adverse event in that class, then I usually switch out of class. Okay. And this is called treatment sharing. I believe there's a word for it. But basically you're sharing with the patient the decision of what to do, and if they're not doing well enough, you switch. And unfortunately, we do have another option. Now, do we know anything else about long term safety? We do know a lot from the clinical trials. Do you know anything from real world safety? Do we have to worry about anything else? The good thing is that these biologics are super targeted, very focused molecules. And in the 18 months of using bimikizumab, there's no signals that have come up. There's very little data from real world registries like coravitus, still a bit too early for that. With other anti IL 17s like secucinomab or ixicizumab, we're not seeing any safety signals long term. We're not seeing malignancy or increase in Canada infections or mace. It just doesn't occur. And we're not seeing a reactivation of tuberculosis, especially in those areas and countries where tuberculosis is more prevalent. We're not seeing that. So short term safety equals long term safety and comfort for the patients especially. And allows the dermatologist or prescribing physician to sleep at night. Right. I will say that when we ask our gastroenterologist, because secucinum was tested for Crohn's disease and did not work, and there were a few patients who even had a little exacerbation, they will not allow us to use 17 blockers in patients with psoriasis and Crohn's disease. The last thing I want to touch on is what other indications are IL 17 blockers used for and I will say that we have a little bit of experience using them off label for hydratinitis separativa. And now, of course, secuchiniumab has been approved. And as you can see, there is very good efficacy data comparing that to placebo. Bimakizumab, I know, is in trials for hydratnitis. So hopefully that will be another future indication. And of course, the 17 blockers are great for psoriatic arthritis. And what you see here is that secuchemab and executionumab are approved in the US for psoriatic arthritis. Burdeliumab is approved for psoriasis along with the other two IL 17 blockers in the US. And we're waiting for approval of vimicizumab for psoriatic arthritis. Bridalimab is approved Xus as is vimakizumab. But secuchenab isa kizumab are available for psoriatic arthritis. The only one approved to date for hydronitis suprativa is indeed secukenumab. And hopefully we'll be getting more for hydratinitis as well. So with that, I want to thank everyone for participating. Thank you, Ron, for that excellent discussion. And we are delighted to have this expanding armamentarium of, of treatments for psoriasis. Thank you. Thank you very much. Thank.

Therapeutic Hotline: Expert Perspectives on IL17 Inhibitors in Targeted Management of Inflammatory Skin Disorders

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