Dand, N, Duckworth, M, Baudry, D, Russell, A, Curtis, CJ, Lee, SH, Evans, I, Mason, KJ, Alsharqi, A, Becher, G, Burden, AD, Goodwin, RG, McKenna, K, Murphy, R, Perera, GK, Rotarescu, R, Wahie, S, Wright, A, Reynolds, NJ, Warren, RB, Griffiths, CEM, Smith, CH, Simpson, MA, Barker, JN, Study Group, BADBIR, Study Group, BSTOP and Consortium, PSORT (2018) HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis. Journal of Allergy and Clinical Immunology, 143 (6). 2120 - 2130. ISSN 0091-6749

[thumbnail of HLA-C_06_02 genotype is a predictive biomarker of biologic treatment response in psoriasis.pdf]
HLA-C_06_02 genotype is a predictive biomarker of biologic treatment response in psoriasis.pdf - Accepted Version

Download (2MB) | Preview


BACKGROUND: Biologic therapies can be highly effective for the treatment of severe psoriasis, but response for individual patients can vary according to drug. Predictive biomarkers to guide treatment selection could improve patient outcomes and treatment cost-effectiveness. OBJECTIVE: We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the 2 most commonly prescribed biologics for psoriasis: adalimumab (anti-TNF-α) and ustekinumab (anti-IL-12/23). METHODS: This study uses a national psoriasis registry that includes longitudinal treatment and response observations and detailed clinical data. HLA alleles were imputed from genome-wide genotype data for 1326 patients for whom 90% reduction in Psoriasis Area and Severity Index score (PASI90) response status was observed after 3, 6, or 12 months of treatment. We developed regression models of PASI90 response, examining the interaction between HLA-C*06:02 and drug type (adalimumab or ustekinumab) while accounting for potentially confounding clinical variables. RESULTS: HLA-C*06:02-negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time points (most strongly at 6 months: odds ratio [OR], 2.95; P = 5.85 × 10-7), and the difference was greater in HLA-C*06:02-negative patients with psoriatic arthritis (OR, 5.98; P = 6.89 × 10-5). Biologic-naive patients who were HLA-C*06:02 positive and psoriatic arthritis negative demonstrated significantly poorer response to adalimumab at 12 months (OR, 0.31; P = 3.42 × 10-4). Results from HLA-wide analyses were consistent with HLA-C*06:02 itself being the primary effect allele. We found no evidence for genetic interaction between HLA-C*06:02 and ERAP1. CONCLUSION: This large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.

Item Type: Article
Additional Information: The final accepted manuscript and all relevant information linked to this can be found at; https://www.jacionline.org/article/S0091-6749(18)32780-5/fulltext https://www.sciencedirect.com/science/article/pii/S0091674918327805
Uncontrolled Keywords: Psoriasis, psoriatic arthritis, biologic therapy, genetics, pharmacogenetics, treatment response, HLA, adalimumab, ustekinumab, skin disease
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > RL Dermatology
Divisions: Faculty of Medicine and Health Sciences > School of Medicine
Related URLs:
Depositing User: Symplectic
Date Deposited: 11 Aug 2020 12:39
Last Modified: 11 Aug 2020 12:39
URI: https://eprints.keele.ac.uk/id/eprint/8503

Actions (login required)

View Item
View Item