ACR Meeting Abstracts

ACR Meeting Abstracts

  • Meetings
    • ACR Convergence 2024
    • ACR Convergence 2023
    • 2023 ACR/ARP PRSYM
    • ACR Convergence 2022
    • ACR Convergence 2021
    • ACR Convergence 2020
    • 2020 ACR/ARP PRSYM
    • 2019 ACR/ARP Annual Meeting
    • 2018-2009 Meetings
    • Download Abstracts
  • Keyword Index
  • Advanced Search
  • Your Favorites
    • Favorites
    • Login
    • View and print all favorites
    • Clear all your favorites
  • ACR Meetings

Abstract Number: 0769

Development and Validation of a Combined Clinical and Genetic Risk Score for Interstitial Lung Disease in a Large, Multicenter, Prospective Rheumatoid Arthritis Cohort

Austin Wheeler1, Joshua Baker2, Yangyuna Yang1, Punyasha Roul1, K Wysham3, Grant Cannon4, Gary Kunkel5, Gail Kerr6, Dana Ascherman7, Paul Monach8, Andreas Reimold9, Jill Poole1, Tony Merriman10, Ted R Mikuls11 and Bryant England1, 1University of Nebraska Medical Center, Omaha, NE, 2University of Pennsylvania, Philadelphia, PA, 3VA Puget Sound/University of Washington, Seattle, WA, 4University of Utah and Salt Lake City VA, Salt Lake City, UT, 5University of Utah, Salt Lake City, UT, 6Washington DC VAMC/Georgetown and Howard Universities, Washington, DC, 7University of Pittsburgh, Pittsburgh, PA, 8VA Boston Healthcare System, Boston, MA, 9University of Texas Southwestern Medical Center, Dallas, TX, 10University of Alabama at Birmingham, Birmingham, AL, 11Division of Rheumatology and Immunology, University of Nebraska Medical Center, Omaha, NE

Meeting: ACR Convergence 2023

Keywords: genomics, interstitial lung disease, rheumatoid arthritis

  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print
Session Information

Date: Sunday, November 12, 2023

Title: Abstracts: RA – Diagnosis, Manifestations, & Outcomes I: RA-ILD

Session Type: Abstract Session

Session Time: 2:00PM-3:30PM

Background/Purpose: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an extra-articular manifestation of RA that causes substantial morbidity and mortality. Although some clinical and genetic risk factors (predominantly MUC5B rs35705950) have been identified, there are no routinely used tools for risk stratification. We sought to develop a risk model for ILD in a large, multicenter RA cohort.

Methods: Participants were enrollees in the Veterans Affairs Rheumatoid Arthritis (VARA) registry, a multicenter prospective cohort of U.S. Veterans with RA. Participants were genotyped for single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis, including MUC5B rs35705950 and 11 other SNPs. ILD was validated through systematic medical record review of provider diagnosis, imaging, and biopsy findings. A meta-analytic odds ratio for ILD was calculated for each SNP by pooling results from VARA (N=2386; N=224 ILD) and Juge et al. (N=514; N=272 ILD) (Table 1). A genetic risk score (GRS) was computed from variant alleles weighted by their effect size with ILD, using backwards predictor selection. The GRS was combined with established clinical risk factors (age, sex, smoking history, DAS28-CRP, and RF positivity) using logistic regression to generate the VARA-ILD Combined Risk Score. Internal validation and calibration were completed using bootstrapping techniques to address over-fitting and determine a shrinkage-corrected performance. Model performance was assessed using the area under the receiver operating curve (AUC), and models were compared via nested likelihood ratio tests as well as Akaike and Bayesian information criterion (AIC, BIC).

Results: Of 2,386 participants (89% male, mean age 69.5 years), 9.4% had ILD. VARA-ILD Combined Risk Score containing the GRS (based on 5 SNPs) and clinical factors (Table 2) outperformed clinical risk factors alone in discriminating ILD (AUC 0.686 vs. 0.635, p< 0.001; Figure 1). Following internal validation and bootstrapping, the shrinkage-corrected performance for combined and clinical-only models was 0.675 (95% CI 0.635, 0.709) and 0.623 (95% CI 0.584, 0.651). VARA-ILD Combined Risk Score also outperformed a model including clinical factors and the MUC5B rs35705950 promoter variant alone (AUC 0.648 [95% CI 0.612, 0.681]) based on AIC (1408 vs. 1429) and BIC (1448 vs. 1469). Demonstrating its potential role in ILD screening, utilizing a risk score cut-point of 0.05 (sensitivity 90%) would eliminate 25% (N=582) of participants from undergoing low-yield ILD diagnostic testing.

Conclusion: The VARA-ILD Combined Risk Score, including multiple genetic risk variants, discriminated ILD in a large, multicenter RA cohort better than established clinical risk factors alone. These results demonstrate the potential utility of genetic risk scores in RA-ILD identification and will support further investigation into individualized risk stratification and screening.

Supporting image 1

Abbreviations: ILD (interstitial lung disease), no-ILD (no interstitial lung disease), VARA (Veterans Affairs Rheumatoid Arthritis registry), OR (odds ratio)
Pooled OR obtained by meta-analysis of OR from VARA and Juge et al. 2018, calculated via fixed-effects model.

Supporting image 2

Abbreviations: interstitial lung disease (ILD), RA (rheumatoid arthritis), CI (confidence interval), DAS_28-CRP (disease activity score with 28 joints and c-reactive protein), RF (rheumatoid factor), single nucleotide polymorphism (SNP)

Supporting image 3

Abbreviations: ROC (receiver operating characteristic), ILD (interstitial lung disease), AUC (area under the curve),
P value calculated via nested likelihood ratio test.


Disclosures: A. Wheeler: None; J. Baker: CorEvitas, 2, Cumberland Pharma, 2, Horizon Pharmaceuticals, 5; Y. Yang: None; P. Roul: None; K. Wysham: None; G. Cannon: None; G. Kunkel: None; G. Kerr: AstraZeneca, 2, Aurinia, 6, Horizon, 2, Janssen, 2, Pfizer, 1, Sanofi, 2; D. Ascherman: None; P. Monach: Genentech, 12, Lecture with honorarium, HI-Bio, 2; A. Reimold: None; J. Poole: AstraZeneca, 12, I have received no monies. I received anti-IL-33 monoclonal antibody from AstraZeneca for animal research sutdies.; T. Merriman: None; T. Mikuls: Elsevier, 9, Horizon Therapeutics, 2, 5, Pfizer, 2, Sanofi, 2, UCB Pharma, 2, Wolters Kluwer Health (UpToDate), 9; B. England: Boehringer-Ingelheim, 2, 5.

To cite this abstract in AMA style:

Wheeler A, Baker J, Yang Y, Roul P, Wysham K, Cannon G, Kunkel G, Kerr G, Ascherman D, Monach P, Reimold A, Poole J, Merriman T, Mikuls T, England B. Development and Validation of a Combined Clinical and Genetic Risk Score for Interstitial Lung Disease in a Large, Multicenter, Prospective Rheumatoid Arthritis Cohort [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/development-and-validation-of-a-combined-clinical-and-genetic-risk-score-for-interstitial-lung-disease-in-a-large-multicenter-prospective-rheumatoid-arthritis-cohort/. Accessed .
  • Tweet
  • Click to email a link to a friend (Opens in new window) Email
  • Click to print (Opens in new window) Print

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/development-and-validation-of-a-combined-clinical-and-genetic-risk-score-for-interstitial-lung-disease-in-a-large-multicenter-prospective-rheumatoid-arthritis-cohort/

Advanced Search

Your Favorites

You can save and print a list of your favorite abstracts during your browser session by clicking the “Favorite” button at the bottom of any abstract. View your favorites »

All abstracts accepted to ACR Convergence are under media embargo once the ACR has notified presenters of their abstract’s acceptance. They may be presented at other meetings or published as manuscripts after this time but should not be discussed in non-scholarly venues or outlets. The following embargo policies are strictly enforced by the ACR.

Accepted abstracts are made available to the public online in advance of the meeting and are published in a special online supplement of our scientific journal, Arthritis & Rheumatology. Information contained in those abstracts may not be released until the abstracts appear online. In an exception to the media embargo, academic institutions, private organizations, and companies with products whose value may be influenced by information contained in an abstract may issue a press release to coincide with the availability of an ACR abstract on the ACR website. However, the ACR continues to require that information that goes beyond that contained in the abstract (e.g., discussion of the abstract done as part of editorial news coverage) is under media embargo until 10:00 AM ET on November 14, 2024. Journalists with access to embargoed information cannot release articles or editorial news coverage before this time. Editorial news coverage is considered original articles/videos developed by employed journalists to report facts, commentary, and subject matter expert quotes in a narrative form using a variety of sources (e.g., research, announcements, press releases, events, etc.).

Violation of this policy may result in the abstract being withdrawn from the meeting and other measures deemed appropriate. Authors are responsible for notifying colleagues, institutions, communications firms, and all other stakeholders related to the development or promotion of the abstract about this policy. If you have questions about the ACR abstract embargo policy, please contact ACR abstracts staff at [email protected].

Wiley

  • Online Journal
  • Privacy Policy
  • Permissions Policies
  • Cookie Preferences

© Copyright 2025 American College of Rheumatology