Risk of lung cancer in systemic lupus erythematosus patients with interstitial lung disease: A retrospective cohort study.

Abstract

e20088 Background: Systemic lupus erythematosus (SLE) is a chronic heterogeneous autoimmune disease that may affect virtually any organ system including the joints, skin, kidneys, heart, and lungs. Interstitial lung disease (ILD) is an uncommon pulmonary manifestation of SLE and is seen in other rheumatological diseases such as rheumatoid arthritis (RA). While ILD is a well-established risk factor for lung cancer in RA, its association with lung cancer in SLE remains poorly characterized. This study aims to assess whether ILD in SLE is associated with an increased risk of lung cancer. Methods: We conducted a retrospective cohort study using TriNetX, a multi-institutional, de-identified EHR database, restricted to adults aged ≥18 years. The exposure cohort included SLE patients with ILD while the control cohort included SLE patients without ILD. Patients with drug induced lupus erythematosus, systemic sclerosis, dermatopolymyositis, and prior history of lung cancer were excluded. One-to-one propensity score matching was performed based on age, sex, race, tobacco use, obesity, hypertension, type 2 diabetes mellitus, chronic kidney disease, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, connective tissue diseases, and exposures to medications such as glucocorticoids, immunosuppressants, and antineoplastics. The primary outcome was defined as the development of lung cancer, and the secondary outcome was defined as all cause mortality. Results: After matching, 10,773 patients were included per cohort. Lung cancer occurred in 143 patients in the exposure cohort and 62 patients in the control cohort with a risk ratio of 2.31 (95% CI 1.71-3.10) and an odds ratio of 2.32 (95% CI 1.72-3.14). All-cause mortality occurred in 1947 patients in the exposure group and 1316 patients in the control group with a risk ratio of 1.48 (95% CI 1.39-1.58) and an odds ratio of 1.59 (95% CI 1.47-1.71). Conclusions: ILD in SLE is associated with a 2.3-fold increased risk of lung cancer and a 1.5-fold increased risk of all-cause mortality, with an absolute risk of 1.33% and 18.14% respectively. These findings suggest that chronic pulmonary inflammation and fibrosis in SLE-ILD may drive lung carcinogenesis as is well described in idiopathic pulmonary fibrosis and RA-ILD. Collectively, these results highlight ILD as a clinically meaningful risk marker in SLE patients, supporting targeted lung cancer surveillance in this population.