title: Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.
abstract: 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.
authors.affiliation: Roche Products Ltd, Welwyn Garden City, UK. jianmei.wang@roche.com
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: A T
authors.initials: AT
authors.lastname: Bansal
authors.forename: M
authors.initials: M
authors.lastname: Martin
authors.forename: S
authors.initials: S
authors.lastname: Germer
authors.forename: R
authors.initials: R
authors.lastname: Benayed
authors.forename: L
authors.initials: L
authors.lastname: Essioux
authors.forename: J S
authors.initials: JS
authors.lastname: Lee
authors.forename: A
authors.initials: A
authors.lastname: Begovich
authors.forename: A
authors.initials: A
authors.lastname: Hemmings
authors.forename: A
authors.initials: A
authors.lastname: Kenwright
authors.forename: K E
authors.initials: KE
authors.lastname: Taylor
authors.forename: R
authors.initials: R
authors.lastname: Upmanyu
authors.forename: P
authors.initials: P
authors.lastname: Cutler
authors.forename: O
authors.initials: O
authors.lastname: Harari
authors.forename: J
authors.initials: J
authors.lastname: Marchini
authors.forename: L A
authors.initials: LA
authors.lastname: Criswell
authors.forename: Adam
authors.initials: A
authors.lastname: Platt
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D015850:Interleukin-6; C502936:tocilizumab; D008727:Methotrexate