Atopic dermatitis and inflammatory skin diseaseHLA-C*06:02 genotype is a predictive biomarker of biologic treatment response in psoriasis
Section snippets
Patient population
The study was conducted in accordance with the 2008 Declaration of Helsinki and in the spirit of the 1996 International Conference on Harmonisation in Good Clinical Practice. Ethical approval for this study was granted by The South East London REC 2 Ethics Committee (11/H0802/7). Written informed consent was obtained from all subjects before enrollment.
All participants are adults (>16 years) enrolled in the Biomarkers of Systemic Treatment Outcomes in Psoriasis (BSTOP) study (//www.kcl.ac.uk/lsm/research/divisions/gmm/departments/dermatology/Research/stru/groups/bstop/index.aspx
A prospective observational data resource facilitating predictive genetic biomarker identification in psoriasis
To assess the ability of HLA-C*06:02 to predict different rates of response to adalimumab and ustekinumab, we considered 3320 patients enrolled in the BSTOP study and BADBIR for whom genotype data were available (see the main Methods section). Of these patients, 53.4% were HLA-C*06:02 positive (carrying ≥1 copy of the allele), with 46.6% being HLA-C*06:02 negative. After applying eligibility criteria to ensure that valid baseline and response PASI scores were available, 1326 participants were
Discussion
This study constitutes the largest investigation to date into the pharmacogenetics of biologic response in patients with psoriasis and is the first to use jointly generated clinical and genetic data on different drugs to identify a predictive biomarker with potential clinical utility. We report that the HLA-C*06:02 allele effectively stratifies patients with psoriasis into groups with different profiles of response to the 2 most frequently prescribed biologics: adalimumab and ustekinumab.
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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.
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.
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These authors contributed equally to this work as co-senior authors.
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The members of the BADBIR study group (excluding individually named authors of this work) are Marilyn Benham, Sagair Hussain, Brian Kirby, Linda Lawson, Kathleen McElhone, Anthony Ormerod, and Caroline Owen.
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The members of the PSORT consortium (excluding individually named authors of this work) are Michael R. Barnes, Paola Di Meglio, Richard Emsley, Andrea Evans, Katherine Payne, and Deborah Stocken.