title: Genetic and genomic markers of anti-TNF treatment response in rheumatoid arthritis.
abstract: Despite the success of anti-TNF drugs in the treatment of rheumatoid arthritis, a significant rate of nonresponse remains. Current clinical factors confer little power for predicting response and, in current practice, an unsatisfactory 'trial and error' approach governs therapeutic decisions. Candidate gene and unbiased genome-wide investigations have sought to identify genetic biomarkers that predict who will respond to anti-TNF drugs before the drug is administered. To date, few studies have yielded robust associations; herein, we discuss currently identified associations and the issues that need to be addressed in future investigations including insufficient power and an inadequate measure of disease activity. The potential for alternative predictors of anti-TNF therapy response from transcriptomic and epigenetic data will also be explored.
authors.affiliation: Arthritis Research UK Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Institute of Inflammation & Repair, University Of Manchester, Manchester, M13 9PL, UK.
authors.forename: James
authors.initials: J
authors.lastname: Oliver
authors.affiliation: NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academy of Health Sciences, Manchester, M13 9PL, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Plant
authors.affiliation: Arthritis Research UK Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Institute of Inflammation & Repair, University Of Manchester, Manchester, M13 9PL, UK.
authors.forename: Amy P
authors.initials: AP
authors.lastname: Webster
authors.affiliation: Arthritis Research UK Centre for Genetics & Genomics, Centre for Musculoskeletal Research, Institute of Inflammation & Repair, University Of Manchester, Manchester, M13 9PL, UK.|NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester Academy of Health Sciences, Manchester, M13 9PL, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D057890:Epigenomics / Q000379:methods*; D020869:Gene Expression Profiling / Q000379:methods*; D005819:Genetic Markers; D006801:Humans; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D005819:Genetic Markers; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: GWAS; anti-TNF; biologics; biomarker; prediction; rheumatoid arthritis; treatment response