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

Publication date: Available online 20 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Nick Dand, Michael Duckworth, David Baudry, Alice Russell, Charles J. Curtis, Sang Hyuck Lee, Ian Evans, Kayleigh J. Mason, 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

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 two most commonly prescribed biologics for psoriasis, adalimumab (anti-TNFα) and ustekinumab (anti-IL12/23).

Methods

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.

Results

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^-7) and the difference was greater in HLA-C*06:02 negative patients with psoriatic arthritis (PsA; OR = 5.98, P = 6.89×10^-5). 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^-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.

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