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)
Authors: Alabas Oras A , Mason Kayleigh J , Yiu Zenas Z N , Warren Richard B , Dand Nick , Barker Jonathan N , Smith Catherine H , Grifﬁths Christopher E M ,   the BADBIR and BSTOP study group, Barker Jonathan , Morrison Simon , Bewley Anthony , Evans Ian , Griffiths Christopher , Ahmed Shehnaz , Kirby Brian , Kleyn Elise , Laws Philip , Hampton Philip , Alabas Oras , McElhone Kathleen , Yiu Zenas , Mackenzie Teena , McPherson Tess , Murphy Ruth , Ormerod Anthony , Walton Shernaz , Reynolds Nick , Smith Catherine , Shipman Alexa , Ye Christina , Hughes Olivia , Warren Richard , Strangfeld Anja , Weller Richard , Gupta Girish , Zietemann Vera , Barker Jonathan , Barnes Michael R , Burden A David , Meglio Paola di , Emsley Richard , Evans Anea , Griffiths Christopher E M , Payne Katherine , Reynolds Nick J , Smith Catherine , Stocken Deborah , Warren Richard B 
Published: December 2023

Abstract

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 registered in the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) from 2007 to 2022 on a 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 in patients ≤ 40 years of age) and late-onset psoriasis (LOP) (presenting in patients &gt; 40 years of age). BADBIR patients with available information in BSTOP were categorized as HLA-C*06:02− or HLA-C*06:02 + . 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 in the age at psoriasis onset group [2929 EOP (69%) vs. 1321 LOP (31%)] and 3094 patients in the HLA-C*06:02 status group [1603 HLA-C*06:02+ (52%) vs. 1491 HLA-C*06:02− (48%)]. There was no significant difference between EOP and LOP in drug survival associated with ineffectiveness or AEs for any biologics. However, compared with patients who were HLA-C*06:02−, patients who were HLA-C*06:02 + were less likely to discontinue ustekinumab for reasons associated with ineffectiveness (aHR 0.56, 95% CI 0.42–0.75).

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