HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis

Dand, N. et al. (2019) HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis. Journal of Allergy and Clinical Immunology, 143(6), pp. 2120-2130. (doi: 10.1016/j.jaci.2018.11.038) (PMID:30578879)

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Abstract

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. We sought to test whether HLA-C*06:02, the primary genetic susceptibility allele for psoriasis, predisposes patients to respond differently to the two most commonly prescribed biologics for psoriasis, adalimumab (anti-TNFα) and ustekinumab (anti-IL12/23). The study utilises 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 1,326 patients for whom PASI90 response status (90% reduction in psoriasis area and severity index) 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. HLA-C*06:02 negative patients were significantly more likely to respond to adalimumab than ustekinumab at all time-points (most strongly at 6m: odds ratio (OR) = 2.95, P = 5.85×10 ) and the difference was greater in HLA-C*06:02 negative patients with psoriatic arthritis (PsA; OR = 5.98, P = 6.89×10 ). Biologic naive patients that were HLA-C*06:02 positive and PsA negative demonstrated significantly poorer response to adalimumab at 12m (OR = 0.31, P = 3.42×10 ). 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. 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:Articles
Keywords:HLA, adalimumab, biologic therapy, genetics, pharmacogenetics, psoriasis, psoriatic arthritis, skin disease, treatment response, ustekinumab.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Burden, Professor David
Authors: Dand, N., Duckworth, M., Baudry, D., Russell, A., Curtis, C. J., Lee, S. H., Evans, I., Mason, K. J., Alsharqi, A., Becher, G., Burden, A. D., Goodwin, R. G., McKenna, K., Murphy, R., Perera, G. K., Rotarescu, R., Wahie, S., Wright, A., Reynolds, N. J., Warren, R. B., Griffiths, C. E. M., Smith, C. H., Simpson, M. A., and Barker, J. N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Allergy and Clinical Immunology
Publisher:Elsevier
ISSN:0091-6749
ISSN (Online):1097-6825
Published Online:19 December 2018
Copyright Holders:Copyright © 2018 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma and Immunology
First Published:First published in Journal of Allergy and Clinical Immunology 143(6):2120-2130
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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