• 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, Griffiths Christopher E M CEM Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centr, Catherine H Smith, Michael A Simpson, Jonathan N Barker, BADBIR Study Group, BSTOP Study Group, and PSORT Consortium.
• School of Basic & Medical Biosciences, London, United Kingdom.
• J. Allergy Clin. Immunol. 2019 Jun 1; 143 (6): 2120-2130.

BackgroundBiologic 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.ObjectiveWe 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).MethodsThis 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.ResultsHLA-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.ConclusionThis large observational study suggests that reference to HLA-C*06:02 status could offer substantial clinical benefit when selecting treatments for severe psoriasis.Copyright © 2018. Published by Elsevier Inc.

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