HLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis - 06/06/19
, Jonathan N. Barker, MD, FRCP, FRCPath b, ⁎, ∗ on behalf of the
BADBIR Study Group‡
BSTOP Study Group
and thePSORT Consortium§
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.
Le texte complet de cet article est disponible en PDF.Key words : Psoriasis, psoriatic arthritis, biologic therapy, genetics, pharmacogenetics, treatment response, HLA, adalimumab, ustekinumab, skin disease
Abbreviations used : BAD, BADBIR, BSTOP, GxE, OR, PASI, PASI75, PASI90, PASI100, PsA, UK
Plan
| Supported by PSORT, which is in turn funded by a Medical Research Council (MRC) Stratified Medicine award (MR/L011808/1). The Psoriasis Association (RG2/10), the NIHR Biomedical Research Centre at King's College London/Guy's and St Thomas' NHS Foundation Trust, the Newcastle NIHR Biomedical Research Centre, and the NIHR Manchester Biomedical Research Centre. The British Association of Dermatologists Biologic and Immunomodulators Register (BADBIR) is coordinated by the University of Manchester. BADBIR is funded by the British Association of Dermatologists (BAD). The BAD receives income from Janssen Cilag, AbbVie, Novartis, Samsung Bioepis, Eli Lilly, Celgene, Almirall, and Hexal AG for providing pharmacovigilance services. This income finances a separate contract between the BAD and the University of Manchester who coordinate BADBIR. All decisions concerning analysis, interpretation, and publication are made independently of any industrial contribution. N.D. was partly supported by Health Data Research UK (MR/S003126/1), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council; Economic and Social Research Council; Department of Health & Social Care (England); Chief Scientist Office of the Scottish Government Health and Social Care Directorates; Health and Social Care Research and Development Division (Welsh Government); Public Health Agency (Northern Ireland); British Heart Foundation; and Wellcome. N.J.R.'s laboratory is funded in part by the Newcastle NIHR Biomedical Research Centre, the Newcastle NIHR Medtech, and the In Vitro Diagnostic Co-operative and the Newcastle MRC/EPSRC Molecular Pathology Node. |
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| Disclosure of potential conflict of interest: M.A.S. has a contract of service with Genomics. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 143 - N° 6
P. 2120-2130 - juin 2019 Retour au numéro
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