Men with systemic sclerosis who smoke face greater excess mortality than women
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Key takeaways:
- Men with systemic sclerosis who smoked had greater excess mortality risk than women.
- Among women, smoking has negative dose-dependent relationship with anti-topoisomerase antibodies.
Men with systemic sclerosis who smoke demonstrate a greater risk for death than women with SSc who smoke, according to a study published in RMD Open.
The study also found that, among women with SSc, smoking has a dose-dependent association with lower prevalence of anti-topoisomerase antibodies (ATA).
“Previous cross-sectional studies showed a correlation between smoking and vascular, gastrointestinal or respiratory symptoms in SSc, but these findings were not confirmed in other cohorts,” Jacopo Ciaffi, MD, of the IRCCS Istituto Ortopedico Rizzoli, in Bologna, Italy, and colleagues wrote.
“Elucidating the extent of the impact of smoking on SSc, and whether smoking exerts distinct effects in men and women, or in patients with different disease characteristics, would have important implications for risk stratification,” they added.
To further clarify the relationship between smoking and SSc, Ciaffi and colleagues analyzed data from the European Scleroderma Trials and Research cohort. The researchers compared the disease progression between men and women who smoked and, following clues from previous research, examined the cohort’s ATA levels and anti-citrullinated peptide antibodies.
The study included 12,314 patients (84% women; 35% ever-smokers) followed over a median period of 30 months. The researchers used Kaplan-Meier curves to assess the time to disease progression, while Cox models were used to examine smoking’s influence over a maximum of 15 years of follow-up.
According to the researchers, smoking “significantly compromises survival” among men with SSc (HR = 1.63; 95% CI, 1.23-2.16) but not women (HR = 1.13; 95% CI, 0.97-1.32).
Among women, 34% of those who never smoked were ATA-positive compared with 21% of ever-smokers (P < .001). Lower frequencies of ATA were seen among women with higher smoking exposure, quantified as pack-years (OR = 0.98; 95% CI, 0.97-0.99) and smoking duration (OR = 0.96; 95% CI, 0.95-0.97).
Whether patients were positive for ACA or ATA, they had increased risk for mortality, skin progression and “any organ progression.”
“Our results corroborate the association between smoking and a reduced prevalence of ATA positivity among SSc patients, particularly notable in females,” Ciaffi and colleagues wrote. “The impact of smoking on SSc outcomes is heterogeneous and can be modified by factors like sex and autoantibody status. Given the poor prognosis of ATA-positive patients, the negative relationship between smoking and ATA introduces an additional layer of complexity.
“The advantages of smoking cessation are unquestionable,” they added. “We strongly advocate for the implementation of targeted smoking cessation counseling and effective interventions for all individuals with SSc.”
Perspective
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The relationship between smoking and anti-citrullinated peptide antibody-positive rheumatoid arthritis is well-established. However, the role of smoking in systemic sclerosis disease progression and etiology is not well defined. Given the complex phenotype of disease, risk factors based on various scleroderma antibodies, as well as the differential effect of autoantibody presence on end organ damage in SSc, make smoking an important variable to control and study. Prior studies by Jaeger and colleagues in 3,319 patients with SSc did not observe a role of smoking on cutaneous or pulmonary outcomes.
In this study by Ciaffi and colleagues, the apparently protective influence of smoking on the presence of anti-topoisomerase antibodies (ATA) does not correspond to any beneficial clinical outcome for ever-smokers. Considering that ATA have been traditionally related to aggressive SSc, with a higher risk for interstitial lung disease and increased mortality, the negative association between smoking and ATA is highly intriguing and needs to be further investigated.
In males with SSc who as we already know have much higher disease burden, the data indicate that smoking significantly compromises survival. Smoking cessation strategies in both males and female patients with SSc must be implemented, given the holistic benefits rendered.
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