Study Models Variable Smoking Status and All-Cause Mortality in RA

Compared with the general population, people with rheumatoid arthritis (RA) have a 50% greater mortality risk. Because smoking is a risk factor for RA, some degree of the elevated mortality risk may be explained by the significant numbers of RA patients who are smokers. In a large, population-based study published in Arthritis Care & Research, investigators at the University of Manchester in the UK examined mortality rates among patients with RA and their relation to various diseases.¹ They also examined the association between smoking cessation and these variables.

In general, people who smoke have been found to have an 83% higher risk of mortality compared to people who have never smoked, with smoking linked to premature mortality from numerous diseases—including cardiovascular disease (CVD), lung cancer and other types of cancer, and infection.²

Previous findings suggest that smoking worsens RA symptoms and overall disease severity, and that patients with RA who smoke have an especially elevated risk of CVD.³ In addition, smoking may decrease the effectiveness of both anti-tumor necrosis factor (TNF) agents and disease-modifying anti-rheumatic drugs (DMARDs).⁴

The authors of the current research¹ pulled data on 5,677 patients from a large UK database of primary care medical records. Over 25% of the patients were current smokers; 34% were former smokers, and 40% never smoked.

The findings were as follows:

• Current smokers had a higher risk of all-cause mortality than those who never smoked (hazard ratio [HR]: 1.98; 95% confidence interval [CI], 1.56 to 2.53).
• After adjusting for patient age and sex, the current smokers had a higher risk of death than those who never smoked (HR: 2.18; 95% CI, 1.73 to 2.76) or former smokers (HR: 1.77; 95% CI, 1.43 to 2.20).
• Current smokers had higher mortality due to circulatory disease than those who never smoked (subdistribution hazard ratio [SHR]: 1.96; 95% CI, 1.33 to 2.90) as well as lung cancer (SHR: 23.2; 95% CI, 5.15 to 105).
• Circulatory disease was the major cause of death for the cohort, corresponding with a crude mortality rate of 8.3 per 1,000 person-years (95% CI, 7.3 to 9.4). Rates were generally highest for current smokers.
• Each year following smoking cessation was linked with a reduced risk of all-cause mortality for former heavy smokers (SHR: 0.85; 95% CI, 0.77 to 0.94) and former light smokers (SHR: 0.90; 95% CI, 0.84 to 0.97).
• Each year following smoking cessation was linked with reduced risk of death from circulatory disease in former heavy smokers, and a reduced risk of death from respiratory infection in former light smokers.

Considering the multitude of negative health effects associated with smoking tobacco — effects that are even greater for people with RA — efforts to facilitate smoking cessation are crucial. “This information on the risks of continuing to smoke after receiving a diagnosis of rheumatoid arthritis could be useful in smoking cessation programs,” the authors noted.

Summary and Clinical Applicability

Although previous studies have indicated an increased risk of all-cause mortality in patients with RA who smoke, that research failed to identify a significant link between smoking and CVD mortality. Although the current study did not identify a significant association between current smoking and all-site cancer deaths, the researchers did find that patients with RA who smoke tobacco have an elevated risk of all-cause mortality and death due to lung cancer and circulatory disease.

Study Limitations

• Limited follow-up time led to reduced sample size and study window.
• Researchers relied on an algorithm vs individual classification criteria to identify patients with RA.
• General practitioner records were used to identify smoking information, which could have led to misclassification of smoking exposure.

References

1. Joseph RM, Movahedi M, Dixon WG, Symmons DP. Smoking-related mortality in patients with early rheumatoid arthritis: a retrospective cohort study using the clinical practice research datalink. Arthrit Care Res. 2016;68(11):1598-1606. doi:10.1002/acr.22882
2. Nakajima A, Inoue E, Tanaka E, et al. Mortality and cause of death in Japanese patients with rheumatoid arthritis based on a large observational cohort, IORRA. Scand J Rheumatol. 2010;39:360–7. doi:10.3109/03009741003604542
3. Masdottir B, Jónsson T, Manfredsdottir V, Víkingsson A, Brekkan A, Valdimarsson H. Smoking, rheumatoid factor isotypes and severity of rheumatoid arthritis. Rheumatology. 2000;39:1202-1205. doi:10.1093/rheumatology/39.1.1202
4. Saevarsdottir S, Wedrén S, Seddighzadeh M, et al. Patients with early rheumatoid arthritis who smoke are less likely to respond to treatment with methotrexate and tumor necrosis factor inhibitors: observations from the epidemiological investigation of rheumatoid arthritis and the Swedish rheumatology register cohorts. Arthritis Rheum. 2011;63:26-36. doi:10.1002/art.27758

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