HLA-Cw6 in Psoriatic Arthritis: Clinical Phenotype and Therapeutic Impact

Psoriatic arthritis (PsA) shares genetic features with psoriasis (PsO), with HLA-Cw6 being the main risk allele that may shape its clinical phenotype. This study aimed to evaluate the association between HLA-Cw6 status and clinical features, comorbidities, and treatment outcomes in PsA.

We conducted a retrospective study of 426 patients with PsA who fulfilled the CASPAR criteria and had documented HLA-Cw6 status. Demographic, clinical, laboratory, and treatment-related variables were extracted from medical records. Patients were compared according to HLA-Cw6 positivity using descriptive, bivariate, and multivariate analyses.

HLA-Cw6 was present in 24.6% of the patients. HLA-Cw6-positive individuals were more frequently female (65.7% vs. 46.1%, P =0.001) and showed earlier PsO onset (28.0 vs. 35.3 y, P =0.009) and longer PsO-arthritis latency (17 vs. 9 y, P =0.024). Dactylitis was significantly less common in HLA-Cw6-positive patients (25.7% vs. 38.0%, P =0.022). HLA-Cw6-positive patients received more targeted therapies (1.8 vs. 1.5 drug classes, P =0.014) and had shorter TNFi persistence (17 vs. 36 mo, P =0.044). IL-12/23 inhibitors showed longer persistence in this group, although the difference was not statistically significant. In multivariate models, HLA-Cw6 was independently associated with female sex (OR: 4.11, P =0.003), lower frequency of dactylitis (OR: 0.33, P =0.020), and greater odds of difficult-to-manage PsA (OR: 12.53, P =0.001) and treatment-refractory PsA (OR: 15.39, P =0.001) based on recent EULAR definitions.

HLA-Cw6 identifies a PsA subset with distinctive clinical features and increased therapeutic complexity. These findings support the potential of HLA-Cw6 as a biomarker for PsA characterization and individualized therapy.