title: Using genetic and clinical data to understand response to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study.
abstract: The objective of this review is to report on the progress of the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS) Registry data collection and summarize previous research in understanding therapeutic response to DMARDs using clinical and genetic data. The BRASS Registry, established in 2003, is a large, single-centre, prospective and observational cohort of 1100 RA patients. Patients with either new-onset or established RA disease are recruited from the practices of rheumatologists. Annual visits collect information on demographics, 28-joint DAS-CRP3 (DAS-28-CRP3), medication use, comorbidities and functional status (Modified Health Assessment Questionnaire, Short Form Health Survey 12). Two published studies have utilized BRASS to examine genetic predictors of treatment response. In a cross-sectional study, examining the association between candidate single nucleotide polymorphisms (SNPs) and disease activity in a subset of 120 RA patients on MTX monotherapy, the minor allele of ATIC rs4673993 was associated with low disease activity (P=0.01, DAS-28-CRP3≤3.2). In an international collaboration, 55 BRASS patients receiving anti-TNF therapy were genotyped for 31 SNPs associated with the risk of RA. With our collaborators, we discovered an SNP at the protein tyrosine phosphatase, receptor type, C (PTPRC) gene locus that was associated with EULAR 'good response'. With accurate data collection and the capacity to run genome-wide association studies and SNP analyses, the BRASS Registry has the ability to determine the contribution of genetic variants to disease onset and to assess their usefulness as biomarkers for treatment response and drug toxicity.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital, PBB-B3, 75 Francis Street, Boston, MA 02115, USA. ciannaccone@partners.org
authors.forename: Christine K
authors.initials: CK
authors.lastname: Iannaccone
authors.forename: Yvonne C
authors.initials: YC
authors.lastname: Lee
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Frits
authors.forename: Roberta J
authors.initials: RJ
authors.lastname: Glass
authors.forename: Robert M
authors.initials: RM
authors.lastname: Plenge
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Shadick
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D015415:Biomarkers; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D012042:Registries; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha