Building a Psoriasis Knockout Regimen Around Risankizumab, with Andrew Blauvelt, MD, MBA

Initial reaction was highly positive for the phase 2 KNOCKOUT study data, presented last week at the American Academy of Dermatology (AAD) 2024 Annual Meeting in San Diego, CA. Research presented by investigator Andrew Blauvelt, MD, MBA, formerly of the Oregon Medical Research Center, showed an early, brief dose regimen of 600 mg risankizumab (SKYRIZI) was associated with significantly reduced psoriasis lesions and resident memory T cell levels after 52 weeks.¹

There’s still more to learn about the dosing strategy of KNOCKOUT—and more robust data necessary from later-stage trials before it could impact psoriasis care. But the potential is there.

In the second segment of an interview with HCPLive during AAD 2024, Blauvelt discussed the exclusive nature of effect observed in KNOCKOUT: from his opinion and on the basis of understood biology, this high-dose treatment effect may only be effective with an IL-23 inhibitor like risankizumab.

“I think it’s the fact those particular cell types that are involved in recurrences are more sensitive to IL-23 inhibition, so that’s the key thing there,” Blauvelt said.

Despite the smaller design of this pilot study, Blauvelt did derive some excitement from not only the efficacy findings, but the continued safety of risankizumab at the 600 mg dose.

“For some reason, IL-23 inhibition doesn’t seem to do much in terms of hurting us, and when we increase doses as we did in KNOCKOUT—and by the way, it’s the same dose as that used to initially treat Crohn’s disease,” Blauvelt noted. “So, 600 mg of SKYRIZI is already an FDA-approved dose to initially treat Crohn’s disease.² So I’m like, why aren’t we doing it in psoriasis?”

The answer to that hypothetical is that more evidence is needed, of course. Blauvelt is interested to see what more data will show—potentially, he said, “a completely different way to treat psoriasis.”

“You could maybe hit the disease once a year,” he said. “To get to that point may take years of development, but we may see it development. And I know there’s a lot of patient support for this idea.”

References

1. ^{Kunzmann K. High Risankizumab Induction Dose Rapidly Clears Psoriasis, Reduces Resident Memory Cells. HCPLive. Published March 9, 2023. https://www.hcplive.com/view/risankizumab-dose-clears-psoriasis-resident-memory-cells}
2. ^{Walter K. FDA Appropves Risankizumab For Crohn’s Disease. HCPLive. Published June 17, 2022. https://www.hcplive.com/view/fda-appropves-risankizumab-crohns-disease}