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J Allergy Clin Immunol. 2018 Dec 20. pii: S0091-6749(18)32780-5. doi: 10.1016/j.jaci.2018.11.038. [Epub ahead of print]

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

Author information

1
School of Basic & Medical Biosciences, London, United Kingdom.
2
St John's Institute of Dermatology, Faculty of Life Sciences & Medicine, London, United Kingdom.
3
NIHR Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London, London, United Kingdom; Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
4
Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, University of Manchester, Manchester, United Kingdom.
5
Royal Liverpool and Brodgreen University Hospital Trusts, Liverpool, United Kingdom.
6
Alan Lyell Centre for Dermatology, West Glasgow ACH, Glasgow, United Kingdom.
7
Institute of Infection, Inflammation and Immunity, University of Glasgow, Glasgow, United Kingdom.
8
Aneurin Bevan University Health Board, Gwent, United Kingdom.
9
Department of Dermatology, Belfast City Hospital, Belfast, United Kingdom.
10
Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom; Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom; Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom.
11
Chelsea & Westminster Hospital NHS Foundation Trust, West Middlesex University Hospital, London, United Kingdom.
12
University Hospitals of North Midlands, Stoke-on-Trent, United Kingdom.
13
University Hospital North Durham, Durham, United Kingdom.
14
Centre for Skin Science, University of Bradford, Bradford, United Kingdom; Dermatology Department, St Luke's Hospital, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, United Kingdom.
15
Dermatological Sciences, Institute of Cellular Medicine, Newcastle University Medical School, Newcastle upon Tyne, United Kingdom; Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom; Newcastle MRC/EPSRC Molecular Pathology Node, Newcastle University, Newcastle upon Tyne, United Kingdom.
16
School of Basic & Medical Biosciences, London, United Kingdom. Electronic address: michael.simpson@kcl.ac.uk.
17
St John's Institute of Dermatology, Faculty of Life Sciences & Medicine, London, United Kingdom. Electronic address: jonathan.barker@kcl.ac.uk.

Abstract

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.

KEYWORDS:

HLA; Psoriasis; adalimumab; biologic therapy; genetics; pharmacogenetics; psoriatic arthritis; skin disease; treatment response; ustekinumab

PMID:
30578879
DOI:
10.1016/j.jaci.2018.11.038

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