Knocking out psoriasis with high-dose risankizumab?

High induction dosing of risankizumab was remarkably efficacious in a population of patients with moderate-to-severe psoriasis, according to the interim results of the phase 2 KNOCKOUT trial. Further analyses will provide data on the duration of efficacy and the role of resident-memory T cells in this process.

Dr Andrew Blauvelt (Oregon Medical Research Center, OR, USA) and co-researchers aimed to evaluate whether high-dose IL-23 inhibition results in long-term remission in patients with moderate-to-severe plaque psoriasis [1]. “By hitting hard and early in the treatment course, we may reduce resident-memory T cells in the skin, which are potential drivers for chronic recurrence of psoriasis,” he clarified. He added that IL-23 inhibitors, such as risankizumab, have been associated with long disease-free intervals after drug cessation [2]. In the ongoing, phase 2 KNOCKOUT study (NCT05283135), 20 participants were randomised 1:1 to a single dose of 300 mg or 600 mg risankizumab, subcutaneously administered. Dr Blauvelt presented the interim efficacy outcomes after 40 weeks of treatment [1].

At week 40, 88.9% of the participants achieved Psoriasis Area and Severity Index (PASI)90 and 66.7% of the participants reached PASI100. Dr Blauvelt mentioned that during the execution of this interim analysis, it was unknown if participants were on the 300 mg or the 600 mg dose. “More important, however, is that the mean absolute PASI was 0.6 at week 40,” he added. “We had 1 outlier, a morbidly obese patient who failed all biologics; he achieved an absolute PASI of 10. But everyone else is dropping out. We’re knocking out psoriasis with this initial high dosing.” Finally, there were no safety issues, according to Dr Blauvelt.

Future analyses from this study at week 52 will display how long psoriasis can be knocked out in these patients and whether the number of resident-memory T cells in fact dropped after the cessation of high-dose induction therapy with risankizumab.

1. Blauvelt A, et al. High induction dosing of Risankizumab in patients with moderate-to-severe plaque psoriasis: interim results from the phase 2 KNOCKOUT study (NCT05283135). Late-breaker Session 5, WCD 2023, 3–8 July, Singapore, Singapore.
2. Blauvelt A, et al. JAMA Dermatol. 2020;156:649–658.