High-impact site plaque psoriasis is difficult to treat. Icotrokinra, an oral peptide with high specificity for the interleukin (IL)-23 receptor, demonstrated significantly higher rates of high-impact site psoriasis clearance, versus placebo, with no safety signals, through Week (W)16. Report clinical response rates and safety through 1 year of icotrokinra treatment in participants with high-impact site plaque psoriasis. Participants (≥12 years of age; psoriasis body surface area ≥1%; Investigator's Global Assessment [IGA] ≥2) with at least moderate scalp, genital or hand/foot psoriasis were randomized (2:1) to once-daily icotrokinra 200 mg (N = 208) or placebo (N = 103), with placebo-to-icotrokinra transition at W16 (N = 92). Rates (using nonresponder imputation) of achieving clear/almost clear (0/1) or clear (0) overall skin (IGA), genital (static Physician's Global Assessment of genitalia [sPGA-G]), hand/foot (hf-PGA) psoriasis and absent/very mild (0/1) or absent (0) scalp psoriasis (scalp-specific-IGA [ss-IGA]), modified Nail Psoriasis Severity Index (mNAPSI) percent improvement and safety were assessed through W52. Eighty-eight per cent (275/311) of participants completed treatment through W52. In icotrokinra-randomized participants, response rates increased through W24 and were durable through W52 for overall psoriasis clearance (IGA 0/1 range: 67%-70%) and across high-impact sites (ss-IGA 0/1: 72%-78%; sPGA-G 0/1: 85%-90%; hf-PGA 0/1: 54%-62%); responses were consistent among placebo-randomized participants after transitioning to icotrokinra. High proportions of icotrokinra-randomized participants achieved complete clearance during W24-52 (IGA 0: 44%-51%; ss-IGA 0: 57%-66%; sPGA-G 0: 73%-84%; hf-PGA 0: 44%-58%). Mean mNAPSI improvement increased from W16 (33%) to W52 (62%). Exposure-adjusted rates of participants with ≥1 adverse event (AE) or serious AE through W16 were similar between icotrokinra and placebo, with no increase in AE rates or occurrence of a safety signal through W52. Icotrokinra demonstrated high and durable rates of psoriasis clearance across high-impact sites, with a favourable safety profile, through 1 year.
