Pharmacogenetics of TNF inhibitor response in rheumatoid arthritis utilizing the two-component disease activity score-Reference-Cited by-同舟云学术

Pharmacogenetics of TNF inhibitor response in rheumatoid arthritis utilizing the two-component disease activity score

Published:2020-11 Issue:16 Volume:21 Page:1151-1156
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Gilani Syed SA¹^ORCID,Nair Nisha²³^ORCID,Plant Darren²³^ORCID,Hyrich Kimme²⁴^ORCID,Morgan Ann W⁵^ORCID,Morris Andrew P³^ORCID,Wilson Anthony G⁶^ORCID,Isaacs John D⁷^ORCID,Barton Anne²³^ORCID,Bluett James²³^ORCID,

Affiliation:

1. School of Medicine, University of Manchester, Manchester, M13 9PT, UK

2. NIHR Manchester Biomedical Research Center, Central Manchester NHS Foundation Trust, Manchester Academic Health Science Center, Manchester, M13 9WL, UK

3. Versus Arthritis Centre for Genetics & Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester, M13 9PL, UK

4. Versus Arthritis Center for Epidemiology, Center for Musculoskeletal Research, The University of Manchester, Manchester, M13 9PL, UK

5. School of Medicine, University of Leeds & NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, LS2 9JT, UK

6. School of Medicine & Medical Science, Conway Institute, University College Dublin, Dublin, Dublin 4, Ireland

7. Institute of Translational & Clinical Research, Newcastle University & Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 7RU, UK

Abstract

Aim: TNF inhibitor drugs are a treatment option for rheumatoid arthritis, but response is not universal. Response is typically measured using the composite 4-component (4C) disease activity score 28 (DAS28) which contains more subjective measures. This study used a validated 2-component (2C) DAS28 score to determine whether SNPs associated with response were replicated in the UK population. Materials & methods: A literature review identified TNF inhibitor response SNPs. Linear regression was conducted to replicate associations with 4C or 2C-DAS28 response. Results: Eighteen independent SNPs were analyzed in 1828 patients. One and four associations with 4C and 2C-DAS28 response respectively were identified (p ≤ 0.05). Conclusion: Further genetic associations were replicated using the 2C-DAS28 which may reflect the objective nature of 2C-AS28.

Funder

Medical Research Council

Versus Arthritis

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2020-0043

Reference21 articles.

1. Biologic Therapy for Rheumatoid Arthritis

2. Long-term impact of early treatment on radiographic progression in rheumatoid arthritis: A meta-analysis