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

Christine K. Iannaccone*, Yvonne C. Lee, Jing Cui, Michelle L. Frits, Roberta J. Glass, Robert M. Plenge, Daniel H. Solomon, Michael E. Weinblatt, Nancy A. Shadick

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

63 Scopus citations

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 43.2). 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.

Original languageEnglish (US)
Pages (from-to)40-46
Number of pages7
JournalRheumatology
Volume50
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Anti-tumour necrosis factor
  • Disease-modifying anti-rheumatic drugs
  • Patient registries

ASJC Scopus subject areas

  • Rheumatology
  • Pharmacology (medical)

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