Are High Doses of Skyrizi a Cure for Plaque Psoriasis? | AAD 2024

High doses of Skyrizi (risankizumab) drove plaque psoriasis into remission and dramatically reduced the number of resident memory T cells that play a role in the disease coming back, according to results presented this morning at the annual meeting of the American Academy of Dermatology in San Diego,

Andrew Blauvelt, M.D., MBA

Andrew Blauvelt, M.D., MBA, the lead investigator who presented the study, said high-dose Skyrizi can’t be characterized as a cure for plaque psoriasis now because in this study the disease came “trickling back” in the second year of follow-up. But he said there was reason to hope that it could be a cure in people who haven’t had plaque psoriasis for very long.

“It’s the hit-it-hard, hit-it-early hypothesis, and we see it in medicine. You don't wait for the disease to establish itself,” Blauvelt said.

The results were from a small study of 20 patients with plaque psoriasis conducted at a single center and so inherently preliminary. Blauvelt, a veteran researcher, is the president and owner of Oregon Medical Research Center in Portland, a business that advises drug companies about clinical trial research, with a focus on a skin conditions. Blauvelt described the AbbVie, the marker of Skyrizi, as a partner in the high-dose Skyrizi study.

Blauvelt’s presentation was one of 18 in the late-breaking abstracts session of the meeting. Researchers — and the companies whose products they have studied — covet inclusion in the late-breaking abstract session. Thousands of the dermatologists attending AAD meeting go to at least part of the three-hour late-breakers session, and the meeting's organizers have deemed the research worthy of the spotlight.

Blauvelt has presented findings from this study, dubbed KNOCKOUT, before, but he said this morning's presentation included some not previously shared data comparing the 10 study participants treated with 300 milligram (mg) doses, which is twice the standard dose of Skyrizi, to the 10 study participants who treated with 600 mg doses.

The results showed greater improvement in plaque psoriais in the 300 mg group in the first weeks of the trial when the patients were being treated, but then the 600 mg group catches up. Blauvelt noted that the patients in the 600 mg group had more severe cases of plaque psoriasis than those in the 300 mg group. The Psoriasis Area and Severity Scale (PASI) is a standard scale for measuring psoriasis severity, especially in clinical trials. The average PASI of the patients in the 300 mg group was 17.1. In the 600 mg group it was 20.

"I think if the groups were clinically similar, we would have seen the 600 mg group do better than the 300 mg group," Blauvelt wrote in an email after his presentation.

As he explained in the presentation, the patients in the KNOCKOUT study were treated with Skyrizi three times: at enrollment, four weeks later and then 12 weeks later (Weeks 0, 4 and 16). The results he presented today were assessments of the patients a year after they were enrolled (Week 52), or 36 weeks after they were lasted treated.

One of the predicates of the study, as described by Blauvelt, is that particular types of T cells, called resident memory T cells, are responsible for recurrences of psoriasis and, furthermore, those T cells are influenced by interleukin (IL)-23, one of the many types of interleukins, proteins that play a crucial, mediating role in the immune response. Plaque psoriasis is one of the autoimmune disorders caused by a dysregulated immune response. Skyrizi inhibits IL-23.

Blauvelt showed colorful, maplike visualized data generated by RNA-based technology that identifies T cells levels in skin tissue. Those images, and some charts, showed a share decline in resident memory T cells.

“You can see right away it looks like nonlesional skin 52 weeks out," he said. Some of the presented data showed an especially steep decline in a particular type of resident memory T cell, called type 17, that may be especially instrumenal in cause plaque psoriasis, Blauvelt said.

After 52 weeks of follow-up, 43% of the patients in the study were rated at PASI 100 (a measure of the improvement of the PASI score), which means that their psoriasis plaques had resolved and they had cleared skin. Blauvet said the safety data for the high doses of Skyrizi were similar to that for the normal dose.

When a member of the audience asked whether Skyrizi was a cure, Blauvelt demurred.

“I don't think it's cure is the quick answer because this is a two year study, and those eight patients that were still clear at week 52, [although] three or four of them are still clear far into the second year, half of them have trickled back, so the disease is trickling back, but it's taking a long time. I expect everybody to trickle back,” said Blauvelt. It is likely that there are still some remaining resident memory T cells in the skin tissue that was affected by psoriasis, he said.