Oral Icotrokinra for Plaque Psoriasis in Adults and Adolescents.

BACKGROUND

Icotrokinra, a targeted oral peptide that selectively binds the interleukin-23 receptor, is under investigation for the treatment of plaque psoriasis.

METHODS

We conducted a phase 3, double-blind, randomized, placebo-controlled trial involving adults and adolescents (≥12 years of age) with moderate-to-severe plaque psoriasis, as defined by all the following: a total body-surface area of psoriasis involvement of at least 10%, a Psoriasis Area and Severity Index (PASI) score of at least 12 (range, 0 to 72, with higher scores indicating a greater extent or severity of psoriasis), and an Investigator's Global Assessment (IGA) score of at least 3 (range, 0 [clear skin] to 4 [severe disease]). Participants were assigned in a 2:1 ratio to receive icotrokinra at a dose of 200 mg once daily through week 24 or placebo through week 16 followed by transition to icotrokinra. The coprimary end points were an IGA 0/1 response (IGA score of 0 or 1 with ≥2-point reduction from baseline) and a PASI 90 response (≥90% reduction from baseline in the PASI score) at week 16.

RESULTS

A total of 684 participants underwent randomization (456 to the icotrokinra group and 228 to the placebo group). At week 16, a total of 65% of the participants receiving icotrokinra and 8% of those receiving placebo had an IGA 0/1 response, and 50% and 4%, respectively, had a PASI 90 response (P<0.001 for both comparisons). Complete clearance of skin at week 16 was significantly more likely with icotrokinra than with placebo (IGA score of 0, 33% vs. 1%; PASI 100 response [100% reduction from baseline in the PASI score], 27% vs. <1%; P<0.001 for both comparisons). The percentage of participants with at least one adverse event through week 16 was 49% in each group; the most common adverse events in each group were nasopharyngitis and upper respiratory tract infection. The exposure-adjusted incidence of adverse events was consistent through week 24.

CONCLUSIONS

Selective blockade of the interleukin-23 receptor with the targeted oral peptide icotrokinra resulted in a significantly higher incidence of skin clearance at week 16 than placebo among adults and adolescents with moderate-to-severe plaque psoriasis. Longer-term data will provide a more complete understanding of the benefit-risk profile of icotrokinra. (Funded by Johnson & Johnson; ICONIC-LEAD ClinicalTrials.gov number, NCT06095115.)See also in NEJM Evidence: Targeted Oral Peptide Icotrokinra for Psoriasis Involving High‑Impact Sites.