The association of age at psoriasis onset and HLA-C*06:02 with biologic survival in patients with moderate-to-severe psoriasis: a cohort study from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR)

BACKGROUND: Few studies have used real-world data to investigate the association between biologic therapy survival and age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis. The robustness of these studies is limited by small sample size, short follow-up and diverse safety and effectiveness measures.

OBJECTIVES: To describe biologic survival and explore whether the response to biologics is modified by age at psoriasis onset or HLA-C*06:02 status in patients with moderate-to-severe psoriasis.

METHODS: Data from patients in the UK and the Republic of Ireland registering to the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007-2022 on first course of adalimumab, etanercept, secukinumab or ustekinumab with at least 6 months' follow-up and a subset of BADBIR patients with available HLA-C*06:02 information registered to Biomarkers and Stratification To Optimise outcomes in Psoriasis (BSTOP) were analysed. Patients aged ≥50 years at treatment initiation were classified into early onset psoriasis (EOP; presenting ≤40 years of age) and late onset (LOP; presenting > 40 years of age); BADBIR patients with available information in BSTOP were categorised into HLA-C*06:02-ve and HLA-C*06:02+ve. Biologic survival was defined as treatment discontinuation associated with ineffectiveness or occurrence of adverse events (AEs). Adjusted survival function and hazard ratio (aHR) with 95% confidence interval (CI) were estimated using a flexible parametric model to compare discontinuing therapy between age at psoriasis onset and HLA-C*06:02 groups. Each model included exposure (biologics), effect modifier (age at onset or HLA-C*06:02 status), interaction terms and several baseline demographic, clinical and disease severity covariates.

RESULTS: Final analytical cohorts included 4250 patients (2929 [69%] EOP vs. 1321 [31%] LOP) and 3094 patients (1603 [52%] HLA-C*06:02+ve vs. 1491 [48%] HLA-C*06:02-ve). There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, HLA-C*06:02+ve compared with HLA-C*06:02-ve patients were less likely to discontinue ustekinumab associated with ineffectiveness 0.56 [0.42, 0.75].

CONCLUSIONS: HLA-C*06:02 but not age at psoriasis onset is a predictive biomarker for biologic survival in psoriasis patients. Findings from this large cohort provide further, important information to aid clinicians using biologic therapies to manage psoriasis patients.