番茄社区

At this year's American College of Rheumatology (ACR) annual meeting, new data were presented on interleukin (IL)-23-targeting treatments for psoriatic arthritis (PsA).

In this second of four exclusive episodes, 番茄社区 brought together three leaders in the field: moderator , of Oregon Medical Research Center in Portland, is joined by , of the SKiN Centre for Dermatology in Peterborough, Ontario, and , of Case Western Reserve University in Cleveland for a virtual roundtable discussion on two studies looking at patients' quality of life with guselkumab (Tremfya), along with pooled data examining 1-year outcomes with risankizumab (Skyrizi).

Following is a transcript of their discussion:

Blauvelt: Hello everyone. My name is Dr. Andy Blauvelt. I'm a dermatologist and president of Oregon Medical Research Center in Portland, Oregon. This is a large clinical trial center. I also have a lot of experience taking care of psoriasis patients with and without psoriatic arthritis. Joining me today are Melinda Gooderham from Peterborough, Canada, who also runs a large clinical practice and clinical trial center, and Dr. Neil Korman from Case Western Reserve University in Cleveland. So, welcome to the two of you.

Now we're going to talk about the new abstracts from the ACR on IL-23 blockers in psoriatic arthritis. So here we're gonna be discussing two abstracts, one concerning guselkumab and one concerning risankizumab, selective IL-23 blockers, both approved for psoriatic arthritis.

So in the first abstract, the investigators looked at guselkumab's effect on sort of quality-of-life measures, including work productivity and daily activity over time on guselkumab. So they looked here at 2-year data. So patients who have been compared to baseline, looking at these measures and then over 2 years of being on guselkumab, what is happening with their activity level, their work productivity, and so forth.

The summary was that in these measures of work productivity and daily activity, they were either maintained or improved from week 24, which had been reported previously up to the 2-year time point. One of the particularly interesting things is they looked at the employment level of the patients from baseline and then 2 years later on guselkumab, and it increased by over 20% during that time period -- the employment of the patients over time. So clearly showing in this abstract that patients do better in a number of different measures in their life and important things for just daily living.

Melinda, can you give us your thoughts on this abstract -- what you think about it?

Gooderham: Yeah, it's interesting because I was an investigator in this, I didn't do the joint assessments because I had a rheumatologist doing that part, but I was part of this study, so it's nice to see these results coming out.

What struck me about this poster was number one, the high rate of unemployment at baseline in this patient population, like 80% -- more than 80%, 90% unemployed. But by 2 years this changed. And like you said, over 20% of patients became employed by the end of 2 years.

So that was really nice to see that change in patients' lives, because we really did see that improvement over time. And I did have patients who started off unemployed as their skin was also clearing too, so it's PsA but they also did have skin benefits here, improving their confidence, improving their ability, and getting back to work, which I think is a huge success.

Blauvelt: Yeah, I mean, I have particular examples of PsA patients who are just disabled. I mean, they have a guitar player who has enthesitis and they can't really play without being well controlled. And patients with severe Achilles enthesitis, where they just can't walk well, they can't work out with that kind of pain. It really can be ... I think dermatologists need to really ask some of those questions about how the PsA may be affecting their [patients'] lives.

Neil, what are your comments about how PsA may affect people's lives in this abstract?

Korman: Yeah, there's no question about it. We don't give this enough credence, but certainly I have many patients, as you just described, Andy, who have major effects on their life and they will tell you about it.

One of the more common ones is the obese patient who says they've started attempting to get their lives in order and try to go on a diet and lose weight, but they can't move, they can't exercise at all. So they're stuck. And I mean, this is a very, very big deal. So I think this is important data. I'm sure it's important data for them to have to give to insurance companies to be able to convince them of the value of this therapy.

Blauvelt: One thing that irritates me always is sort of PsA is considered "just a more important disease" than psoriasis. I think we all know that just having psoriasis and not PsA really sucks too. It really ruins people's lives.

But you made the comment about the insurance companies, and we just had to sort of prove to them over the years that psoriasis by itself is an important disease and a significant impact on people's lives. I mean, I know we're talking about PsA, but what's been your experience with fighting insurance companies about maybe psoriasis coverage?

Korman: It's a continuous ongoing battle. In the last year or so, I've finally gotten a pharmacist on our team. So they put together these amazing letters that usually win on the first try and save myself and my staff an enormous amount of time and energy.

Blauvelt: Right. Melinda, any comments about that?

Gooderham: Yeah, it's sometimes, you know, you look at that unemployment rate and much of it is the disability of the joints, but it's also the skin involvement, but also mental health. There's so much anxiety and depression in that population. So when someone's not working and they're on disability, sometimes it's a whole mix of those things. So sometimes we have to bring that into the coverage issue too. It's not just about clearing the scanner, improving the joints, it's also about improving mental health.

Blauvelt: Right. Well, it's nice that the investigators here really just showed a big difference with employment. I think that's one of the more interesting aspects that I haven't quite seen yet.

Gooderham: And also, one other thing is it's studies like this why I like to argue about treating earlier. It's easier to get a 25-year-old employed than a 65-year-old -- and one argument always for being more aggressive early on in diagnosis.

Blauvelt: Absolutely. I think that's really important. We often wait too long, I think.

All right, well, we're gonna switch to another IL-23 blocker abstract, and this is risankizumab. There were two phase III trials in psoriatic arthritis called and. And what the authors did here was simply an integrated analysis, a pooled analysis from both of those trials and reported it out at week 52.

The dosing here is 150 mg every 12 weeks. So that's basically the same as the psoriasis dose. And the bottom line is that patients continue to do well. They do better from the earlier time points up to the week-52 time point.

And so not a lot of new things here, but I wanted to bring this abstract in just to talk again about it. We see that these two IL-23 blockers performing really well in psoriasis -- guselkumab and risankizumab. Do you see them competing in this psoriatic arthritis space with [IL-]17 blockers and TNF [tumor necrosis factor] blockers?

Neil, what do you think about risan[kizumab] for PsA?

Korman: Yeah, I think the data is pretty good. It may not be good enough that -- I bet if they did, no one's gonna do this, but if they did a non-inferiority trial, for example, of [risankizumab] versus, or either one of these versus one of the [IL-]17s, I'm confident for PsA that they'd be non-inferior.

And conversely, if somebody attempted to put together a trial to prove that the -17s were statistically significantly "superior," I don't think they could necessarily design that study. So I think it's right at the edge where the numbers, they look a little numerically better for PsA data than IL-23 data. But in my hands in the clinic, I don't see a whole lot of difference.

Blauvelt: Yeah, I think one important thing here is that we had used risankizumab first for PsA and the data were, I think, more poor there. And so we mentally thought, oh, the selective [IL-]23s will be like uste[kinumab, Stelara] -- they won't be as good.

The other piece of information is they failed -- the -23s have failed with ank spon, ankylosing spondylitis, and so that's kind of influencing us a little bit.

But Melinda, what do you think about this topic of -23s for PsA?

Gooderham: Yeah, I agree. It would be really hard to show superiority just because of the nature of these and how we measure it. So the ACR scores are limited in so many ways to be able to show that. I certainly have patients who were in the clinical trials who did amazing with their joints. I had one patient with 50 tender swollen joints at the beginning to zero after a year, and she continues to do well. So it really works well for some patients.

I've also had some patients who did not do as well with their joints, and I've had to switch them to IL-17 inhibitors, but it wasn't a home run there either. Some patients just have more difficult disease to treat. But I agree that IL-23 is a great option for patients who have both skin and joints, and I've seen really good improvements.

Blauvelt: Yeah, I kind of feel that way too. I think one of the things I try to teach is that they're different than ustekinumab. I think the data, the trial data, is different, and then my experience data is also different for those two compared to ustekinumab.

So yeah, I think it's a good discussion, especially when we see better skin responses with the -17s and -23s versus TNF. We see better safety in general. It really does push me towards the newer biologics versus the old TNFs, even in PsA patients.

So any other thoughts on this topic of drug of choice -23 versus -17s versus -17 or versus TNFs?

Gooderham: Yeah, I think -23s are a great way to start because you have the safety and then if you don't hit a home run, then you have some other options. That's kind of how I go through my day with my patients.

Blauvelt: Great. All right. Well, thank you for joining me and discussing these two interesting abstracts from the ACR, and we'll talk some more in the future on this topic. Thank you.

Watch episode one of this series: Safety and Efficacy of IL-17 Blockers for Psoriatic Arthritis

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