Abstract
BackgroundTNFα inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, however at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFα inhibitors in patients with rheumatoid arthritis (RA).Methodology and Principal FindingsIn the DANBIO Registry we identified 237 TNFα inhibitor naïve patients with RA (81% women; median age 56 years; disease duration 6 years) who initiated treatment with infliximab (n = 160), adalimumab (n = 56) or etanercept (n = 21) between 1999 and 2008 according to national treatment guidelines. Clinical response was assessed at week 26 using EULAR response criteria. Based on literature, we selected 213 INDELS potentially related to RA and treatment response using the GeneVa® (Compugen) in silico database of 350,000 genetic variations in the human genome. Genomic segments were amplified by polymerase chain reaction (PCR), and genotyped by Sanger sequencing or fragment analysis. We tested the association between genotypes and EULAR good response versus no response, and EULAR good response versus moderate/no response using Fisher’s exact test. At baseline the median DAS28 was 5.1. At week 26, 68 (29%) patients were EULAR good responders, while 81 (34%) and 88 (37%) patients were moderate and non-responders, respectively. A 19 base pair insertion within the CD6 gene was associated with EULAR good response vs. no response (OR = 4.43, 95% CI: 1.99–10.09, p = 7.211×10−5) and with EULAR good response vs. moderate/no response (OR = 4.54, 95% CI: 2.29–8.99, p = 3.336×10−6). A microsatellite within the syntaxin binding protein 6 (STXBP6) was associated with EULAR good response vs. no response (OR = 4.01, 95% CI: 1.92–8.49, p = 5.067×10−5).ConclusionGenetic variations within CD6 and STXBP6 may influence response to TNFα inhibitors in patients with RA.
Highlights
Tumor necrosis factor alpha (TNFa) inhibitor therapy has greatly improved outcome in patients with moderate and severe rheumatoid arthritis (RA) [1,2,3]
The aim of the present study was to investigate the association between insertions and deletions (INDELS) and response to TNFa inhibitors in patients with RA treated in routine care
Patients were included in the study if they had RA according to the ACR 1987 criteria [27] and had available DNA samples drawn before start of TNFa inhibitor treatment
Summary
Tumor necrosis factor alpha (TNFa) inhibitor therapy has greatly improved outcome in patients with moderate and severe rheumatoid arthritis (RA) [1,2,3]. Drug response is variable and approximately 30% of patients with RA do not respond to TNFa inhibitors or fail to maintain initial response [1,2,3,4]. Since the completion of the Human HapMap Project, there has been a burst in the number of pharmacogenetic studies aiming to identify genetic variation associated with response to TNFa inhibitors in patients with RA. TNFa inhibitor therapy has greatly improved the treatment of patients with rheumatoid arthritis, at least 30% do not respond. We aimed to investigate insertions and deletions (INDELS) associated with response to TNFa inhibitors in patients with rheumatoid arthritis (RA)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call