Age, Sex, Smoking Status, and Presence of Autoantibodies Risk Factors for ILD Among Patients With RA

Recent study results published in Rheumatic Musculoskeletal Diseases Open revealed consistent associations between age, sex, smoking status, and autoantibodies in the development of interstitial lung disease (ILD) among patients with rheumatoid arthritis (RA). These findings emphasize the importance of screening individuals with these risk factors for early detection and intervention.

Researchers conducted a systematic review, spanning from January 2011 to July 2021, to identify patients with RA who exhibited certain risk factors at the individual level, and reported on factors that could potentially indicate the highest risk of developing ILD among these patients.

A total of 23 studies across 31 publications were included in the final analysis (17 full-papers, 1 letter, 5 conference abstracts).

A total of 15 studies reported autoantibodies among patients with and without ILD. A longitudinal study reported a strong association between rheumatoid factor (RF) positivity and ILD among 923 patients (odds ratio [OR], 1.728; 95% CI, 1.042-2.867).

A separate study reported that RF positivity at baseline with titres greater than 15 U/mL was associated with ILD, indicating a higher risk as titres increased.

Interstitial lung disease was also associated with anti-citrullinated protein antibody (ACPA) positivity at titres greater 15 U/mL and with combined RF and ACPA positivity, regardless of titre.

A total of 12 studies reported on the age of patients with and without ILD. A single study reported that individuals over the age of 50 were at greater risk for ILD compared with those aged 50 years or less (hazard ratio (HR), 2.20; 95% CI, 1.04-4.65). Additionally, patients aged over 40 years at the time of RA onset were associated with a greater risk for ILD vs those aged 40 years or less (HR, 2.55; 95% CI, 1.11-5.90).

Of the 11 studies reporting sex differences among patients with and without ILD, 4 reported a significant association between male sex and ILD in adjusted analyses. Additionally, one large longitudinal study reported an association between male sex and ILD in an unadjusted analysis.

Nine studies reported potential associations between smoking and ILD. Among 4 adjusted analyses, 3 compared patients with and without a history of smoking and found no association with ILD, while the remaining analysis reported a strong association (P =.001).

Nongenetic biomarker matrix metalloproteinase 7, along with autoantibodies, demonstrated a significant association with ILD development according to an adjusted analysis of a 2 center, prospective cohort study (ORs for both cohorts, 1.82 and 1.50).

“Identification of patient-level factors may aid in the development of a risk algorithm to identify patients at the highest risk of ILD for screening, monitoring and possible early treatment,” the study authors concluded.