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Patients with rheumatoid arthritis (RA) and RA-interstitial lung disease are at an increased risk of lung cancer, according to the results of a retrospective, matched cohort study.

Previous studies have found RA patients have a higher risk of developing lung cancer compared to the general population. However, these studies did not determine whether this risk is independent of other factors like smoking. To address this gap, the authors of a new study investigated the relationship between RA and lung cancer while controlling for other risk factors. They also evaluated whether RA patients with interstitial lung disease (ILD) experience an even greater risk of lung cancer.¹

Drawing data from the Veterans Health Administration

Investigators recruited patients from Veterans Health Administration (VA) databases between January 2000 to December 2019. An administrative-based algorithm was used to identify RA patients using International Classification of Diseases codes (ICD), rheumatologist diagnoses, disease-modifying anti-rheumatic drug (DMARD) use, and/or seropositivity. Patients with ICD codes for other inflammatory conditions were excluded. 

The RA-ILD cohort was divided into two groups: prevalent and incident. The prevalent group included patients diagnosed with ILD before the implementation of the RA algorithm, and the incident group included those diagnosed after.

A total of 72,795 RA patients and 633,937 matched controls were identified. Patients with RA were mostly male (87.6%) and White (81.8%) with a mean age of 63 years. In the RA cohort, 757 patients were diagnosed with prevalent RA-ILD. These were matched to 5,931 controls. Controls were matched on birth year, VA enrollment year, and gender.

The RA-ILD cohort was older, with a mean age of 67.4, and had a higher comorbidity burden than the RA group. Smoking history and seropositivity rates were comparable between the RA and RA-ILD groups.

The primary outcome measure for the study was to test whether RA and RA-ILD patients had an elevated risk of lung cancer compared to non-RA patients. 

RA and RA-ILD patients face higher risk of lung cancer

The study follow-up period included 4,481,323 patient-years and 17,099 incident lung cancers. The rate of incident lung cancer was higher in the RA group (58.4/10,000 patient-years) than in the non-RA group (35.6/10,000 patient-years). This association held after adjusting for confounders (adjusted hazard ratio (aHR) 1.58, 95% CI 1.52-1.64), restricting the analysis to never-smokers (aHR 1.65, 95% CI 1.22-2.24), using only incident RA cases (aHR 1.54, 95% CI 1.44-1.65), and excluding controls with idiopathic pulmonary fibrosis (IPF) diagnosis code (aHR 1.61, 95% CI 1.55-1.68). The risk of lung cancer-related mortality in the RA group was also increased compared to controls (aHR 1.58, 95% CI 1.51-1.66).

The prevalent RA-ILD cohort had an elevated rate of incident lung cancer over the follow-up period compared to controls (109.3/10,000 patient-years and 31.8/10,000 patient-years, respectively). After adjusting for confounders, the prevalent RA-ILD cohort had av higher risk of lung cancer than those without RA (aHR 3.25, 95% CI 2.13-4.95). The prevalent RA-ILD group had an elevated lung cancer mortality rate compared to the non-RA group (82.7 vs. 24.5 per 10,000 patient-years) in the adjusted model (aHR 3.46, 95% CI 2.17-5.52).

Limitations of the study include a lack of female participants, missing data on smoking duration and intensity, a small sample size of never-smokers, a lack of data on lung cancer phenotypes, and the possibility of misclassifications in the queried databases. Additionally, socioeconomic status and pollutant exposure were not considered.

Bryant England, MD, PhD, associate professor in the division of rheumatology and immunology at the University of Nebraska in Omaha and the study鈥檚 corresponding author, told MedPage today, 鈥淧rior studies have found an increased risk of lung cancer in RA, but our study really highlighted that RA patients with ILD are at an especially increased risk of lung cancer.鈥� 

Based on the study findings, Dr. England advocates for updated screening guidelines, 鈥淕iven RA and RA-ILD patients are at higher risk of lung cancer, we need to determine whether (and how) lung cancer screening strategies should be modified for these populations.鈥� He added, 鈥淭hese findings more strongly affect how we monitor and manage RA and RA-ILD patients over time. For example, an important question is whether we should obtain low-dose chest CT scans even if patients don鈥檛 fulfill the current USPSTF criteria.鈥� 

The authors call for future studies to focus on the relationship between disease activity and lung cancer risk, as well as whether lung cancer surveillance and early intervention for RA-ILD reduce mortality.

Published: October 24, 2024