Impact and Timing of Smoking Cessation on Reducing Risk of Rheumatoid Arthritis Among Women in the Nurses’ Health Studies

OBJECTIVE: To investigate the impact and timing of smoking cessation on developing rheumatoid arthritis (RA) and serologic phenotypes. METHODS: We investigated smoking cessation and RA risk in the Nurses' Health Study (NHS) (1976-2014) and the NHS II (1989-2015). Smoking exposures and covariates were obtained by biennial questionnaires. Self-reported RA was confirmed by medical record review for American College of Rheumatology/European League Against Rheumatism criteria. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RA serologic phenotypes (all, seropositive, seronegative) according to smoking status, intensity, pack-years, and years since cessation. RESULTS: Among 230,732 women, we identified 1,528 incident cases of RA (63.4% of which were seropositive) during 6,037,151 person-years of follow-up. Compared with never smoking, current smoking increased the risk of all RA (multivariable HR 1.47, 95% CI 1.27-1.72) and seropositive RA (HR 1.67, 95% CI 1.38-2.01) but not seronegative RA (HR 1.20, 95% CI 0.93-1.55). An increasing number of smoking pack-years was associated with an increased trend for the risk of all RA (P < 0.0001) and seropositive RA (P < 0.0001). With increasing duration of smoking cessation, a decreased trend for the risk of all RA was observed (P = 0.009) and seropositive RA (P = 0.002). Compared to recent quitters (<5 years), those who quit ≥30 years ago had an HR of 0.63 (95% CI 0.44-0.90) for seropositive RA. However, a modestly increased risk of RA was still detectable 30 years after quitting smoking (for all RA, HR 1.25 95% CI 1.02-1.53; for seropositive RA, HR 1.30 95% CI 1.01-1.68; reference, never smoking). CONCLUSION: These results confirm that smoking is a strong risk factor for developing seropositive RA and demonstrate for the first time that a behavior change of sustained smoking cessation could delay or even prevent seropositive RA.