Researchers have developed a new combined risk score to better diagnose patients with rheumatoid arthritis (RA) who have an increased risk of pulmonary fibrosis (PF). The study, “Validation of a Genetic Risk Score Combined With Clinical Variables for Predicting Pulmonary Fibrosis in Early Rheumatoid Arthritis,” was published in Arthritis Care & Research.
According to the authors, about one in 10 RA patients also experience RA-associated interstitial lung disease (RA-ILD). However, scientists have struggled to accurately predict which patients are at high risk of the severe expression of the disease.
“Despite the identification of several clinical risk factors, such as older age, male sex, smoking history, severe articular disease and autoantibody seropositivity, particularly in usual interstitial pneumonia, there remains a lack of standardized tools for risk stratification in RA-ILD,” the authors wrote.
The new model, which incorporates both clinical risk factors and a genetic risk score (GRS), outperforms clinical factors alone in identifying patients with early RA who have an elevated risk of the complication. Researchers developed the combined risk score using the Veterans Affairs Rheumatoid Arthritis (VARA) registry.
They externally validated the tool in an analysis of 1,118 patients from a cohort in northern Sweden who were diagnosed with early RA between 1996 and 2016. The team collected clinical data and performed genotyping of 12 single-nucleotide polymorphisms related to idiopathic pulmonary fibrosis (IPF) and determined that 60 of these individuals had pulmonary fibrosis.
The research team reported that in addition to known factors, such as age, disease activity and rheumatoid factor positivity, the single nucleotide polymorphisms MUC5B (rs35705950) and FAM13A (rs2609255) were significantly associated with PF risk.
Like the VARA RA-ILD study, the researchers observed that combining GRS with clinical factors improved the predictive value of the score. The GRS alone had an area under the curve (AUC) of 0.62, while the combined risk score had an AUC of 0.75 (P <0.001). Additionally, each unit increase in the GRS increased the risk of RA-PF by 2.6-fold (95% CI, 1.6, 4.5).
When comparing results of the two cohorts, the authors noted that the VARA cohort included primarily male individuals, while the Swedish cohort had a higher percentage of women. In both cohorts, the majority of patients had a smoking history, but the VARA cohort had a higher percentage.
“Despite the differences in these cohorts, the performance of the GRS and combined risk score were similar,” the authors wrote. “Thus, this RA-ILD combined risk score appears to be a promising tool for us to risk-stratify RA-ILD and inform RA-ILD screening approaches.”
