The Risk of Lung Cancer in RA and RA-Associated Interstitial Lung Disease

At December 17, 2024

Arthritis Rheumatol. 2024 Dec;76(12):1730-1738. doi: 10.1002/art.42961. Epub 2024 Aug 16.

Rebecca T Brooks 1, Brent Luedders 2, Austin Wheeler 2, Tate M Johnson 2, Yangyuna Yang 2, Punyasha Roul 2, Apar Kishor Ganti 2, Namrata Singh 3, Brian C Sauer 4, Grant W Cannon 4, Joshua F Baker 5, Ted R Mikuls 2, Bryant R England 2

Affiliations
• 1 Mayo Clinic, Rochester, Minnesota.
• 2 The Department of Veterans Affairs Nebraska-Western Iowa Health Care System and the University of Nebraska Medical Center, Omaha.
• 3 University of Washington, Seattle.
• 4 Salt Lake City Department of Veterans Affairs and the University of Utah.
• 5 Corporal Michael J. Crescenz Department of Veterans Affairs and the University of Pennsylvania, Philadelphia.
Abstract

Objective: We aimed to evaluate lung cancer risk in patients with rheumatoid arthritis (RA) and RA-interstitial lung disease (ILD).

Methods: We performed a retrospective, matched cohort study of RA and RA-ILD within the Veterans Health Administration (VA) between 2000 and 2019. Patients with RA and RA-ILD 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.

Results: We matched 72,795 patients with RA with 633,937 patients without RA (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 (adjusted hazard ratio [aHR] 1.58 [95% confidence interval (CI) 1.52-1.64]), which persisted in never smokers (aHR 1.65 [95% CI 1.22-2.24]) and in those with incident RA (aHR 1.54 [95% CI 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 [95% CI 2.13-4.95]) than RA without ILD (aHR 1.57 [95% CI 1.51-1.64]). Analyses of both prevalent and incident RA-ILD produced similar results (RA-ILD vs non-RA aHR 2.88 [95% CI 2.45-3.40]).

Conclusion: RA was associated with a >50% increased risk of lung cancer, and those with RA-ILD represented a particularly high-risk group with an approximate three-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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