Genetic and genomic predictors of anti-TNF response

• Published in: Pharmacogenomics Vol. 12; no. 11; pp. 1571 - 1585
• Main Authors: Prajapati, Rita, Plant, Darren, Barton, Anne
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2011
• Subjects: Anti-Inflammatory Agents - therapeutic use; Antibodies, Monoclonal - therapeutic use; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Biomarkers, Pharmacological; Care and treatment; Dosage and administration; Genetic aspects; Genetic Association Studies; Genetic research; Genetic variation; Humans; Identification and classification; Inflammatory Bowel Diseases - drug therapy; Infliximab; Patients; Polymorphism, Single Nucleotide - genetics; Tumor necrosis factor inhibitors; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.11.114

The introduction of anti-TNF therapy has dramatically improved the outlook for patients suffering from a number of inflammatory conditions including rheumatoid arthritis and inflammatory bowel disease. Despite this, a substantial proportion of patients (approximately 30-40%) fail to respond to these potentially toxic and expensive therapies. Treatment response is likely to be multifactorial; however, variation in genes or their expression may identify those most likely to respond. By targeted testing of variants within candidate genes, potential predictors of anti-TNF response have been reported; however, very few markers have replicated consistently between studies. Emerging genome-wide association studies suggest that there may be a number of genes with modest effects on treatment response rather than a few genes of large effect. Other potential serum biomarkers of response have also been explored including cytokines and autoantibodies, with antibodies developing to the anti-TNF drugs themselves being correlated with treatment failure.