Age-Specific Risk Factors for Cancer in a Long-Term Korean Cohort of Patients with Ankylosing Spondylitis Treated with TNF Inhibitors.

Background/Objectives: Tumor necrosis factor (TNF) inhibitors are widely used in ankylosing spondylitis (AS), but data on cancer risk in this young population remain limited. We aimed to identify factors associated with cancer during TNF inhibitor therapy and evaluate age-specific risks in Asian patients with AS. Methods: We analyzed 810 AS patients who initiated TNF inhibitors between 2003 and 2023 at a Korean tertiary center. Cox regression assessed cancer predictors; when sparse data limited conventional models, Firth's penalized likelihood was applied. Kaplan-Meier curves compared cumulative cancer incidence by age. Results: Over a mean follow-up of 7 years, cancer incidence was 323 per 100,000 person-years. Patients with cancer were older (48.6 vs. 39.0 years, p = 0.002) and more likely to have hypertension (33.3% vs. 14.6%, p = 0.041). In multivariable analysis, only age remained significant, with each year increasing hazard by 5.7%. Stratified analyses showed rising risks: HR 2.0 (≥30 vs. <30 years), 3.6 (≥40), 6.0 (≥50), and 8.8 (≥60). Risk profiles differed by age: in patients aged <40 years, female sex and elevated ESR were associated with cancer, while in patients aged ≥40 years, only age was associated. Thyroid cancer predominated in younger patients and lung cancer in older patients. Conclusions: In this long-term Korean cohort of patients with AS treated with TNF inhibitors, age was the primary independent risk factor, though determinants varied across age groups. These findings underscore the need for age-specific cancer risk assessment in AS.