Front Immunol. 2026 Sep 18;17:1917350. doi: 10.3389/fimmu.2026.1917350. eCollection 2026.
ABSTRACT
BACKGROUND: Xeligekimab, a monoclonal antibody targeting interleukin-17A (IL-17A), has demonstrated high efficacy in treating moderate-to-severe plaque psoriasis. However, the detailed response patterns across anatomical regions, treatment targets, and patient-reported outcomes remain incompletely elucidated.
METHODS: This post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled trial (CHICTR2100043223) included 420 Chinese patients randomized 2:1 to receive subcutaneous xeligekimab 200 mg every 2 weeks or placebo for 12 weeks, followed by open-label xeligekimab through week 52. Regional Psoriasis Area and Severity Index (PASI) responses across four anatomical sites, treatment targets [ideal target: PASI 90 or absolute PASI ≤3 or body surface area (BSA) ≤1% or Physician’s Global Assessment (PGA) 0/1; acceptable target: PASI 75 or absolute PASI ≤5 or BSA ≤3% or PGA 0/1/2; sustained remission: BSA = 0% or PGA = 0 for ≥6 months], and Dermatology Life Quality Index (DLQI) domain-specific improvements were comprehensively analyzed.
RESULTS: Xeligekimab produced rapid improvements across all PASI dimensions by week 4, with induration (-60.1%), scaling (-61.9%), and erythema (-50.3%) versus -5.3% to -7.7% for placebo (all P < 0.001). By week 12, reductions reached -91.1%, -90.9%, and -82.3%, respectively. Regional analysis showed that head lesions responded most rapidly (PASI 90: 84.2% at week 12), with week 52 regional PASI 90 rates ranging from 81.2% to 92.1%. Ideal and acceptable target achievement rates reached 86.6% and 94.9% at week 12 versus 4.6% and 9.9% for placebo (both P < 0.001), increasing to 91.0% and 98.0% by week 52. The median time to sustained remission was 48 weeks for xeligekimab. By weeks 52 and 60, sustained remission rates reached 50.1% and 54.1%, respectively. Patient-reported outcomes demonstrated rapid and comprehensive improvement across all DLQI functional dimensions by week 4, with low-impact rates exceeding 90% by week 12 for physical symptoms (97.0% for symptoms, 92.0% for pruritus), psychological burden (98.0%), daily activities (97.1%-98.2%), social functioning (98.0%), work/study (97.0%), and treatment burden (99.0%), all significantly superior to placebo (all P < 0.001).
CONCLUSION: Xeligekimab provides rapid symptom resolution across all clinical dimensions, high and sustained achievement of treatment targets, and comprehensive restoration of quality of life.
CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn, identifier CHICTR2100043223.
PMID:42827493 | PMC:PMC13630728 | DOI:10.3389/fimmu.2026.1917350
