TOPLINE:

A combined model incorporating a genetic risk score and clinical risk factors outperformed the genetic risk score alone in predicting pulmonary fibrosis in patients with early rheumatoid arthritis (RA) and could be used to identify individuals at elevated risk for this complication.

METHODOLOGY:

• Researchers externally validated a previously developed clinical and genetic risk score in an independent cohort of patients with RA to determine whether these scores reliably predict pulmonary fibrosis and could support targeted screening.
• They analyzed data from an inception cohort of 1115 patients diagnosed with early RA in northern Sweden between 1996 and 2016, of whom 60 had pulmonary fibrosis.
• Clinical data collected included Disease Activity Score in 28 joints, pharmacologic treatments, and smoking history at baseline and during multiple follow‑up visits; rheumatoid factor status was assessed at baseline using routine laboratory methods.
• Genotyping was performed for 12 single‑nucleotide polymorphisms associated with idiopathic pulmonary fibrosis, including the MUC5B promoter variant.
• Pulmonary fibrosis was diagnosed through high‑resolution CT based on reticular patterns, honeycombing, or traction bronchiectasis, with occasional ground‑glass opacities, in the lungs of patients presenting with symptoms or abnormalities on plain chest radiographs.

TAKEAWAY:

• When five single-nucleotide polymorphisms from the previously established genetic risk score were tested, two — MUC5B (odds ratio [OR], 3.02; P < .001) and FAM13A (OR, 1.82; P < .01) — were independently associated with increased risks for RA-associated pulmonary fibrosis.
• Each unit increase in the genetic risk score was associated with a 2.6‑fold increase in the odds of RA‑associated pulmonary fibrosis (P < .0001).
• In the combined model, age, rheumatoid factor positivity, and the genetic risk score all remained significant predictors of pulmonary fibrosis (P < .05).
• The combined risk score showed significant discriminative ability for RA-associated pulmonary fibrosis, with an area under the curve (AUC) of 0.75 (95% CI, 0.69-0.81), outperforming the genetic risk score, which showed an AUC of 0.62 (95% CI, 0.54-0.69); this difference was statistically significant (P < .001).

IN PRACTICE:

“These results emphasize the potential role of combined genetic and clinical risk scores to inform RA-ILD [interstitial lung disease] screening strategies,” the authors wrote.

SOURCE:

The study was led by Mikael Brink, PhD, MD, Umeå University, Umeå, Sweden. It was published online on November 14, 2025, in Arthritis Care & Research.

LIMITATIONS:

High-resolution CT examinations were not performed randomly or on all included patients but rather selectively on those with abnormalities on plain x-rays or clinical indications suspicious for pulmonary fibrosis. Additionally, these examinations were conducted over almost 20 years, during which methodological improvements could have affected the results. The researchers also refrained from further diagnostic evaluations to differentiate between usual interstitial pneumonia and nonspecific interstitial pneumonia disease patterns.

DISCLOSURES:

The study received support from the Swedish Research Council, King Gustaf V’s 80-Year Fund, the Swedish Rheumatism Association, and Umeå University. Some authors declared receiving grants or contracts, payments or honoraria, support for attending meetings, or consulting fees from and having other ties with various pharmaceutical companies and institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.