Risk of lung cancer in rheumatoid arthritis and in relation to autoantibody positivity and smoking

OBJECTIVE: Lung cancer is a common malignancy in rheumatoid arthritis (RA). Since smoking is a risk factor for both (seropositive) RA and lung cancer, it remains unclear whether RA, in itself, increases lung cancer risk. METHODS: We performed a population-based cohort study of patients with RA and individually matched general population reference individuals identified in Swedish registers and from the Epidemiological Investigation of RA early RA study, prospectively followed for lung cancer occurrence 1995–2018. We calculated incidence rates and performed Cox regression to estimate HRs including 95% CIs of lung cancer, taking smoking and RA serostatus into account. RESULTS: Overall, we included 44 101 patients with RA (590 incident lung cancers, 56 per 100 000), and 216 495 matched general population individuals (1691 incident lung cancers, 33 per 100 000), corresponding to a crude HR (95% CI) of 1.76 (1.60 to 1.93). In subset analyses, this increased risk remained after adjustment for smoking (HR 1.77, 95% CI 1.06 to 2.97). Compared with general population subjects who were never smokers, patients with RA who were ever smokers had almost seven times higher risk of lung cancer. In RA, seropositivity was a significant lung cancer risk factor, even when adjusted for smoking, increasing the incidence 2–6 times. At 20 years, the risk in patients with RA was almost 3%, overall and over 4% for patients who were ever smokers and had at least one RA autoantibody. CONCLUSIONS: Seropositive RA is a risk factor for lung cancer over and above what can be explained by smoking, although residual confounding by smoking or other airway exposures cannot be formally excluded. There is a need for increased awareness and potentially for regular lung cancer screening, at least in a subset of patients with RA.