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

Nick Dand, Michael Duckworth, David Baudry, Alice Russell, Charles J Curtis, Sang Hyuck Lee, Ian Evans, Kayleigh Mason, Ali Al-Sharqi, Gabrielle Becher, Arthur David Burden, Richard Goodwin, Kevin McKenna, Ruth Murphy, Gayathri Perera, Radu Rotarescu, Shyamal Wahie, Andrew Wright, Nick J Reynolds, Richard WarrenCEM Griffiths, Catherine H Smith, Michael A Simpson, Jonathan N W N Barker, The BADBIR Study Group, The BSTOP Study Group, The PSORT Consortium

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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.
Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Early online date20 Dec 2018
DOIs
Publication statusPublished - 2019

Keywords

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

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