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Association of HLA-DRB1 Haplotypes With Rheumatoid Arthritis Severity, Mortality, and Treatment Response

Overview of attention for article published in JAMA: Journal of the American Medical Association, April 2015
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (97th percentile)
  • Good Attention Score compared to outputs of the same age and source (79th percentile)

Mentioned by

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2 news outlets
blogs
2 blogs
twitter
69 X users
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9 Facebook pages

Citations

dimensions_citation
118 Dimensions

Readers on

mendeley
257 Mendeley
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1 CiteULike
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Title
Association of HLA-DRB1 Haplotypes With Rheumatoid Arthritis Severity, Mortality, and Treatment Response
Published in
JAMA: Journal of the American Medical Association, April 2015
DOI 10.1001/jama.2015.3435
Pubmed ID
Authors

Sebastien Viatte, Darren Plant, Buhm Han, Bo Fu, Annie Yarwood, Wendy Thomson, Deborah P. M. Symmons, Jane Worthington, Adam Young, Kimme L. Hyrich, Ann W. Morgan, Anthony G. Wilson, John D. Isaacs, Soumya Raychaudhuri, Anne Barton

Abstract

Advances have been made in identifying genetic susceptibility loci for autoimmune diseases, but evidence is needed regarding their association with prognosis and treatment response. To assess whether specific HLA-DRB1 haplotypes associated with rheumatoid arthritis (RA) susceptibility are also associated with radiological severity, mortality, and response to tumor necrosis factor (TNF) inhibitor drugs. The Norfolk Arthritis Register (NOAR; 1691 patients and 2811 radiographs; recruitment: 1989-2008; 2008 as final follow-up) was used as a discovery cohort and the Early Rheumatoid Arthritis Study (421 patients and 3758 radiographs; recruitment: 1986-1999; 2005 as final follow-up) as an independent replication cohort for studies of radiographic outcome. Mortality studies were performed in the NOAR cohort (2432 patients; recruitment: 1990-2007; 2011 as final follow-up) and studies of treatment response in the Biologics in Rheumatoid Arthritis Genetics and Genomics Study Syndicate cohort (1846 patients enrolled at initiation of TNF inhibitor; recruitment: 2006-2010; 2011 as final follow-up). Longitudinal statistical modeling was performed to integrate multiple radiograph records per patient over time. All patients were from the United Kingdom and had self-reported white ancestry. Sixteen HLA-DRB1 haplotypes defined by amino acids at positions 11, 71, and 74. Radiological outcome using the Larsen score (range: 0 [none] to 200 [severe joint damage]) and erosions of the hands and feet on radiographs, all-cause mortality, and treatment response measured by change in Disease Activity Score based on 28 joint counts and European League Against Rheumatism (EULAR) response. Patients with RA and valine at position 11 of HLA-DRB1 had the strongest association with radiological damage (OR, 1.75 [95% CI, 1.51-2.05], P = 4.6E-13). By year 5, the percentages of patients with erosions of the hands and feet were 48% of noncarriers (150/314) of valine at position 11, 61% of heterozygote carriers (130/213), and 74% of homozygote carriers (43/58). Valine at position 11 also was associated with higher all-cause mortality in patients with inflammatory polyarthritis (hazard ratio, 1.16 [95% CI, 1.03-1.31], P = .01) (noncarriers: 319 deaths in 1398 patients over 17 196 person-years, mortality rate of 1.9% per year; carriers: 324 deaths in 1116 patients in 13 208 person-years, mortality rate of 2.5% per year) and with better EULAR response to TNF inhibitor therapy (OR, 1.14 [95% CI, 1.01-1.30], P = .04) (noncarriers: 78% [439/561 patients] with moderate or good EULAR response; heterozygote carriers: 81% [698/866]; and homozygote carriers: 86% [277/322]). The risk hierarchy defined by HLA-DRB1 haplotypes was correlated between disease susceptibility, severity, and mortality, but inversely correlated with TNF inhibitor treatment response. Among patients with RA, the HLA-DRB1 locus, which is associated with disease susceptibility, was also associated with radiological severity, mortality, and treatment response. Replication of these findings in other cohorts is needed as a next step in evaluating the role of HLA-DRB1 haplotype analysis for management of RA.

X Demographics

X Demographics

The data shown below were collected from the profiles of 69 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 257 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 3 1%
Japan 1 <1%
Colombia 1 <1%
Canada 1 <1%
Unknown 251 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 37 14%
Researcher 35 14%
Student > Master 32 12%
Student > Bachelor 29 11%
Student > Postgraduate 16 6%
Other 50 19%
Unknown 58 23%
Readers by discipline Count As %
Medicine and Dentistry 89 35%
Biochemistry, Genetics and Molecular Biology 31 12%
Immunology and Microbiology 24 9%
Agricultural and Biological Sciences 16 6%
Pharmacology, Toxicology and Pharmaceutical Science 7 3%
Other 23 9%
Unknown 67 26%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 69. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 August 2022.
All research outputs
#621,069
of 25,411,814 outputs
Outputs from JAMA: Journal of the American Medical Association
#6,267
of 36,456 outputs
Outputs of similar age
#7,204
of 279,343 outputs
Outputs of similar age from JAMA: Journal of the American Medical Association
#88
of 428 outputs
Altmetric has tracked 25,411,814 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 97th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 36,456 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 72.5. This one has done well, scoring higher than 82% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 279,343 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 97% of its contemporaries.
We're also able to compare this research output to 428 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 79% of its contemporaries.