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

Dand, Nick; Duckworth, Michael; Baudry, David; Russell, Alice; Curtis, Charles J.; Hyuck Lee, Sang; Evans, Ian; Mason, Kayleigh; Alsharqi, Ali; Becher, Gabrielle; David Burden, A.; Goodwin, Richard G.; McKenna, Kevin; Murphy, Ruth; Perera, Gayathri K.; Rotarescu, Radu; Wahie, Shyamal; Wright, Andrew; Reynolds, Nick J.; Warren, Richard B.; Griffiths, Christopher E.M.; Smith, Catherine H.; Simpson, Michael A.; Barker, Jonathan N.; Study Group, BADBIR

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Nick Dand

Michael Duckworth

David Baudry

Alice Russell

Charles J. Curtis

Sang Hyuck Lee

Ian Evans

Ali Alsharqi

Gabrielle Becher

A. David Burden

Richard G. Goodwin

Kevin McKenna

Ruth Murphy

Gayathri K. Perera

Radu Rotarescu

Shyamal Wahie

Andrew Wright

Nick J. Reynolds

Richard B. Warren

Christopher E.M. Griffiths

Catherine H. Smith

Michael A. Simpson

Jonathan N. Barker

BADBIR Study Group


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-a) 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.

Journal Article Type Article
Acceptance Date Nov 27, 2018
Online Publication Date Dec 20, 2018
Publication Date 2019-06
Publicly Available Date May 26, 2023
Journal Journal of Allergy and Clinical Immunology
Print ISSN 0091-6749
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 143
Issue 6
Pages 2120-2130
Keywords Psoriasis, psoriatic arthritis, biologic therapy, genetics, pharmacogenetics, treatment response, HLA, adalimumab, ustekinumab, skin disease
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