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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.

Original publication

DOI

10.1038/tpj.2012.8

Type

Journal article

Journal

Pharmacogenomics J

Publication Date

06/2013

Volume

13

Pages

235 - 241

Keywords

Adult, Antibodies, Monoclonal, Humanized, Antirheumatic Agents, Arthritis, Rheumatoid, Clinical Trials, Phase III as Topic, Female, Genome-Wide Association Study, Humans, Interleukin-6, Male, Methotrexate, Middle Aged, Polymorphism, Single Nucleotide