451 Association between HLA-Cw6 status and response to guselkumab in patients with moderate to severe plaque psoriasis

Abstract

Modestly better responses to ustekinumab, a fully human monoclonal antibody that targets the common p40 subunit of IL-12 and IL-23, were previously reported among psoriasis (PsO) patients (pts) carrying the human leukocyte antigen (HLA)-Cw6 (C*06:02) allele. Guselkumab (GUS) is a fully human monoclonal antibody that binds the p19 subunit of IL-23 and selectively blocks IL-23-mediated signaling. In this study, we set out to test whether better responses to GUS may be similarly observed among pts carrying the HLA-Cw6 allele in large cohorts of pts from the phase 3 VOYAGE 1 and 2 studies that evaluated the efficacy and safety of GUS in pts with moderate to severe plaque PsO. HLA-Cw6 genotype status was determined using a PCR-based method. Responses to GUS at Week 2, 4, 12, 16, 20, 24 and 28 for 519 Caucasian pts, stratified by HLA-Cw6 status, were evaluated. Potential associations between several baseline clinical variables and responses to GUS were also evaluated. Variables demonstrating statistical significance were included as covariates in multivariate regression models evaluating association between HLA-Cw6 status and response to GUS. Both HLA-Cw6-positive (n=260; 50.1%) and HLA-Cw6-negative (n=259; 49.9%) pts demonstrated good response to GUS; 83% vs. 77%, respectively, achieved at least 90% improvement in their baseline Psoriasis Area and Severity Index (PASI 90) at Week 28. HLA-Cw6-positive pts achieved PASI 90 response more rapidly, as this group had a significantly higher percentage of PASI 90 responders at Weeks 8, 12, 16, and 20, and PASI 100 responders at Weeks 8, 12, 16, 24 and 28, compared to the HLA-Cw6-negative group. The largest differences in proportion of responders between the two groups were observed at Week 8 (18%) for PASI 90 and at Week 20 (15.2%) for PASI 100 responses. These results demonstrate a distinct, but modest, positive association between response to IL-23 blockade with GUS and HLA-Cw6-positive status among PsO pts.