Switch to IL-23 Blocker Yields Deep Responses in Recalcitrant Plaque Psoriasis

Many plaque psoriasis patients that responded inadequately to an interleukin (IL)-17 inhibitor had deep and durable responses after switching to the IL-23 inhibitor risankizumab (Skyrizi), according to trial results presented at the American Academy of Dermatology (AAD) annual meeting.

MedPage Today brought together three expert leaders in the field: moderator Melinda Gooderham, MSc, MD, a dermatologist and clinical researcher from Peterborough, Ontario, is joined by Jennifer Soung, MD, a dermatologist and director of clinical research at Southern California Dermatology in Orange County, and Geeta Yadav, MD, founder of FACET Dermatology in Toronto, for a virtual roundtable discussion. This second of four exclusive episodes focuses on the results from this long-term prospective trial.

Following is a transcript of their remarks:

Gooderham: Hello, I'm Melinda Gooderham. I'm a dermatologist and clinical researcher from Peterborough, Ontario, at the SKiN Centre for Dermatology and an assistant professor at Queen's University. I wanted to welcome you to this roundtable discussion on top news from AAD 2023, and I'm delighted to have with me today Dr. Geeta Yadav, who is the founder and medical director at FACET Dermatology in Toronto and a lecturer at the University of Toronto, and Dr. Jennifer Soung, who is the director of clinical research at Southern California Dermatology and is on clinical faculty at Harbor-UCLA.

So let's move on to the next late-breaker presentation about the efficacy and safety after 52 weeks in psoriasis, patients switching to risankizumab after suboptimal response to secukinumab [Cosentyx] and ixekizumab [Taltz]. So this was an AbbVie sponsored study that was basically an open-label 52-week study where they took patients who had received secukinumab or ixekizumab for at least 6 months, yet had failed to have an adequate response.

So they had residual disease with body surface area [BSA] between 3% and 10%, sPGA [static Physician Global Assessment] 2 or 3, and then they were immediately put onto risankizumab at the beginning of the study. So there was no washout associated with the treatment.

And there were some differences in the baseline characteristics and demographics in this study, which was called the aIMM study. If you compare it to the pivotal trials, you do see lower disease compared to patients who are washed out and starting a clinical trial. So the median PASI [Psoriasis Area and Severity Index] was 6 compared to 18 in the pivotal trials, the BSA median was about 6% compared to 20% in the clinical trials. So although the disease characteristics at baseline were a bit lower, this is on treatment. So very recalcitrant patients.

So to be in the study, you had to have the suboptimal response. So we have 100% of patients failing one biologic, but we also had 40% of patients that had two or greater prior biologic treatments. So these are those heavily treated recalcitrant patients that entered this study.

And the primary endpoint being the sPGA 0/1, so clear or almost clear at week 16, there was about 56% of patients. So you could gain response in these IL-17 failures by giving them an IL-23 inhibitor.

What also was noted while at week 16 -- the percentage of patients with completely clear skin was about 20%. A bit lower than the pivotal trials, but this is a different population. Those patients with DLQI [Dermatology Life Quality Index] 0/1 was about 40%, and the PSS [Psoriasis Symptom Score] of 0 was again 20%, similar to the clear skin.

What they saw over the 52 weeks is there was still some more improvement. The sPGA 0/1 at week 52 went up to 63% and completely clear skin in 26% of patients by week 52 after failing that IL-17 inhibitor.

So some pretty good responses for a difficult-to-treat population. And one other nice thing is that there were no new safety issues despite the fact that they weren't washed out of their first treatment, they just switched right over as we would do in the real world. So it's always good to get more safety information on these treatments in this patient population.

Soung: Yeah, I found the results really interesting. It's a very practical question, right? We have many biologics that have high skin clearance rates, and when you look at meta analyses, we really see our IL-17s and 23s at the top. However, one thing I want to point out in this trial is that I don't think all IL-17s are the same, and they put both secukinumab and ixekizumab together in this population. So really important to note that 62% of patients were considered secukinumab inadequate responders and 38% were considered inadequate responders to ixekizumab.

Gooderham: Fantastic.

Yadav: Yeah, I agree with that. The baseline demographics in a few ways are a little bit different, because they're tough responders, but also the drugs that they were on before being put into this trial, it's not equivalent. They're not equal necessarily in how we might think of their efficacy. But I think what's more, it's not clear if that's because more people are prescribing secukinumab so you tend to see more of those failures, or is it because that truly there's maybe an efficacy difference between these two drugs?

And I always find that hard with NMEs [new molecular entities], right? Because it sort of depends on who designed it, how that initial trial data was collected and how it was interpreted. But I take your point, I think that's an important thing to highlight with this poster for people that are kind of trying to assess this data critically.

Gooderham: Yeah, that's really important. And there's still so much to get from this study. In the eight minutes they have to present a late-breaker, you don't get all of the information. I think one of the questions at the end was, could this be related to weight? What is different about these patients? There was no difference in weight from the patient population seen here versus the pivotal trial. So it didn't seem to be weight-related. But I think we'll see a lot more coming out of this study as they do some more post hoc analyses to help us figure out who is that patient that's not going to respond to IL-17, but may still respond to interleukin-23.

So something to stay tuned for there. So keep an eye out for future meetings for the aIMM study. So thanks, guys.

Watch episode one here: Trial of Novel TYK2 Inhibitor Hits Its Endpoint in Plaque Psoriasis

Comment