The VARA-ILD Combined Risk Score has demonstrated superiority to clinical risk factors alone for diagnosing interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA), Austin Wheeler, MD, said during his abstract presentation at ACR Convergence 2023 on November 12.

“Although some clinical and genetic risk factors (predominantly MUC5B rs35705950) have been identified, there are no routinely used tools for risk stratification,” Dr Wheeler said. He and colleagues sought to create a more accurate tool to stratify the risk among patients with RA of developing ILD, a primary contributor to morbidity and mortality in this population.

From the large, multicenter Veterans Affairs Rheumatoid Arthritis (VARA) registry of U.S. veterans with RA, the researchers drew a cohort of 2386 participants, predominantly male (89%), with a mean age of 69.5 years; 9.4% had ILD. The investigators genotyped participants for single nucleotide polymorphisms (SNPs) associated with idiopathic pulmonary fibrosis, computing a genetic risk score (GRS) from genetic variants. The GRS was then combined with clinical risk factors such as age, sex, smoking history, rheumatoid factor positivity and scores on the DAS28-CRP, to generate the VARA Combined Risk Score.

The VARA-ILD Combined Risk Score containing the GRS (based on 5 SNPs) and clinical factors outperformed clinical risk factors alone in discriminating ILD (AUC 0.686 vs. 0.635, p< 0.001) and also outperformed a model including clinical factors and the MUC5B rs35705950 promoter variant alone, Dr Wheeler noted.

Utilizing a risk score cut-point of 0.05 (with a sensitivity of 90%), some 25% of participants could be spared low-yield ILD diagnostic testing, the investigators found.

“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,” Dr Wheeler concluded.

Reference:

"Development and Validation of a Combined Clinical and Genetic Risk Score for Interstitial Lung Disease in a Large, Multicenter, Prospective Rheumatoid Arthritis Cohort," Veterans Affairs Rheumatoid Arthritis (VARA), November 2023.