The Risk of Lung Cancer in Rheumatoid Arthritis and Rheumatoid Arthritis-Associated Interstitial Lung Disease.

To evaluate lung cancer risk in rheumatoid arthritis (RA) and RA-interstitial lung disease (ILD). We performed a retrospective, matched cohort study of RA and RA-ILD within the Veterans Health Administration (VA) between 2000-2019. RA and RA-ILD patients were identified with validated administrative-based algorithms then matched (up to 1:10) on age, gender, and VA enrollment year to individuals without RA. Lung cancers were identified from a VA oncology database and the National Death Index. Conditional Cox regression models assessed lung cancer risk adjusting for race, ethnicity, smoking status, Agent Orange exposure, and comorbidity burden among matched individuals. Several sensitivity analyses were performed. We matched 72,795 RA to 633,937 non-RA persons (mean age 63 years; 88% male). Over 4,481,323 patient-years, 17,099 incident lung cancers occurred. RA was independently associated with an increased lung cancer risk (aHR 1.58 [1.52, 1.64]), which persisted in never-smokers (aHR 1.65 [1.22, 2.24]) and incident RA (aHR 1.54 [1.44, 1.65]). Compared to non-RA controls, prevalent RA-ILD (n=757) was more strongly associated with lung cancer risk (aHR 3.25 [2.13, 4.95]) than RA without ILD (aHR 1.57 (1.51, 1.64]). Analyses of both prevalent and incident RA-ILD produced similar results (RA-ILD vs. non-RA aHR 2.88 [2.45, 3.40]). RA was associated with a >50% increased risk of lung cancer, and RA-ILD represented a particularly high-risk group with an approximate 3-fold increased risk. Increased lung cancer surveillance in RA, and especially RA-ILD, may be a useful strategy for reducing the burden posed by the leading cause of cancer death.

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