Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis

• Published in: The pharmacogenomics journal Vol. 13; no. 3; pp. 235 - 241
• Main Authors: Wang, J, Bansal, A T, Martin, M, Germer, S, Benayed, R, Essioux, L, Lee, J S, Begovich, A, Hemmings, A, Kenwright, A, Taylor, K E, Upmanyu, R, Cutler, P, Harari, O, Marchini, J, Criswell, L A, Platt, Adam
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2013; Nature Publishing Group
• Subjects: 692/699/249/1313/498; 692/700/565/1436/434; Adult; Analysis; Antibodies, Monoclonal, Humanized - administration & dosage; Antirheumatic Agents - administration & dosage; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - pathology; Biomedical and Life Sciences; Biomedicine; Clinical Trials, Phase III as Topic; Drug therapy; Female; Gene Expression; Genetic polymorphisms; Genome-Wide Association Study; Human Genetics; Humans; Interleukin-6 - genetics; Interleukin-6 - metabolism; Male; Methotrexate - administration & dosage; Middle Aged; Oncology; original-article; Pharmacotherapy; Polymorphism, Single Nucleotide; Prognosis; Psychopharmacology; Rheumatoid arthritis; genetic; genome; tocilizumab; rheumatoid arthritis
• ISSN: 1470-269X; 1473-1150
• DOI: 10.1038/tpj.2012.8

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease affecting the joints. A heterogeneous response to available therapies demonstrates the need to identify those patients likely to benefit from a particular therapy. Our objective was to identify genetic factors associated with response to tocilizumab, a humanized monoclonal antibody targeting the interleukin (IL)-6 receptor, recently approved for treating RA. We report the first genome-wide association study on the response to tocilizumab in 1683 subjects with RA from six clinical studies. Putative associations were identified with eight loci, previously unrecognized as linked to the IL-6 pathway or associated with RA risk. This study suggests that it is unlikely that a major genetic determinant of response exists, and it illustrates the complexity of performing genome-wide association scans in clinical trials.