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

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.

Figure 1

Cumulative hazard of lung cancer in RA and RA‐ILD versus matched non‐RA controls. Cumulative hazard of incident lung cancer in (A) RA versus matched non‐RA controls and (B) RA‐ILD versus matched non‐RA controls. Non‐RA comparators were matched on age, gender, and Veterans Health Administration enrollment year. All models were adjusted for race, ethnicity, smoking status, Agent Orange exposure, and Rheumatic Disease Comorbidity Index (lung disease was not included in the Rheumatic Disease Comorbidity Index score in RA‐ILD analyses). aHR, adjusted hazard ratio; ILD, interstitial lung disease; RA, rheumatoid arthritis.

Figure 2

Cumulative hazard of lung cancer death in RA and RA‐ILD versus matched non‐RA controls. Cumulative hazard of lung cancer death in (A) RA versus matched non‐RA controls and (B) RA‐ILD versus matched non‐RA controls. Non‐RA comparators were matched on age, gender, and Veterans Health Administration enrollment year. All models were adjusted for race, ethnicity, smoking status, Agent Orange exposure, and Rheumatic Disease Comorbidity Index (lung disease was not included in the Rheumatic Disease Comorbidity Index score in RA‐ILD analyses). aHR, adjusted hazard ratio; ILD, interstitial lung disease; RA, rheumatoid arthritis. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.42961/abstract.