Cigarette Smoking Increases the Risk of All-Cause Mortality in Male Patients with Systemic Sclerosis: An Analysis of the EUSTAR Cohort

Jacopo Ciaffi¹, Sophie Liem², Saad Ahmed², Eva Hoekstra², Piotr Wiland³, Tatsuya Atsuma⁴, Gabriella Szucs⁵, Alexandra Balbir-Gurman⁶, Laszlo Czirjak⁷, Elisabetta Zanatta⁸, Ina Koetter⁹, Joerg Henes¹⁰, marco Matucci Cerinic¹¹, Paolo Airò¹², Francesco Ursini¹³, Thomas Huizinga² and Jeska de Vries-Bouwstra², ¹IRCCS Istituto Ortopedico Rizzoli, Bologna, Italy, ²Leiden University Medical Center, Leiden, Netherlands, ³Wroclaw University of Medicine, Wroclaw, Poland, ⁴Hokkaido University, Department of Rheumatology, Endocrinology and Nephrology, Sapporo, Japan, ⁵University of Debrecen, Department of Rheumatology, Debrecen, Hungary, ⁶Rheumatology Institute, Rambam Health Care Campus and Rappaport Faculty of |Medicine, Technion, Haifa, Israel, ⁷Dept. Rheumatol Immunol, Medical School, university of Pecs, Pecs, Hungary, ⁸Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Padova, Padua, Italy, ⁹University Hospital Eppendorf, Prisdorf, Germany, ¹⁰University Hospital Tuebingen, Tuebingen, Germany, ¹¹Unit of Immunology, Rheumatology, Allergy and Rare diseases, IRCCS San Raffaele Hospital, Milan, Milan, Italy, ¹²Spedali Civili di Brescia, Scleroderma UNIT, UOC Reumatologia ed Immunologia Clinica, Piazzale Spedali Civili 1, 25123, Brescia, Italy, ¹³IRCCS Istituto Ortopedico Rizzoli, Bologna, Netherlands

Meeting: ACR Convergence 2023

Keywords: Mortality, risk factors, Smoking, Systemic sclerosis

Session Information

Date: Sunday, November 12, 2023

Title: (0609–0672) Systemic Sclerosis & Related Disorders – Clinical Poster I: Research

Session Type: Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Cigarette smoking is an established risk factor for mortality in the general population but, in systemic sclerosis (SSc), evidence about the role of smoking in the evolution of the disease is lacking. In this study, we aim to determine whether smoking is a risk factor for reduced survival in SSc and whether smoking can contribute to the excess mortality observed in male patients compared with females.

Methods: The multinational EUSTAR database was analysed. Individuals with missing or inconsistent information about smoking status were excluded. The included patients were categorised as “never-smokers” or “ever-smokers” at the baseline visit. After stratification for sex, Kaplan–Meier estimates of time until death in ever-smokers and never-smokers were compared using a log-rank test. Follow-up time was censored at 15 years. Cox proportional hazards models adjusted for age were used to assess the risk of mortality in men and women, expressed as hazard ratios (HR) and 95% confidence intervals (95% CI). Incidence rates of mortality and 95% CI were calculated in men and women according to their smoking habit, considering never-smoking women as the reference category to determine the relative risk (RR) of death.

Results: Of the 12314 included patients (Table 1), 10393 were females (84%) and 1921 were males (16%). Overall, 807 deaths were observed during 47162 patient-years of follow-up in females and 241 deaths were observed in males over 6878 patient-years of follow-up, accounting for a mortality rate of, respectively, 28% and 46%. Survival was significantly lower in ever-smokers compared to never-smokers (68% vs 70%, p= 0.001, Figure 1). This difference was accounted for by the males: survival was 50% in ever-smoking males compared to 60% in never-smoking males (p < 0.001) (Figure 2). No difference was found in ever-smoking and never-smoking female patients (survival rate 75% vs 71%, p= 0.207). In Cox regression analysis adjusted for age, smoking was associated with increased risk of mortality (HR 1.63, 95% CI 1.23 – 2.16, p= 0.001) in male patients and no association emerged in women (HR 1.13, 95% CI 0.96 – 1.32, p= 0.148). Incidence rate for mortality was 1.77/100 patient-years in never-smoking women (reference category), 1.56/100 patient-years in ever-smoking women (RR= 0.88), 2.53/100 person-years in never-smoking men (RR= 1.43), 4.10/100 person-years in ever-smoking men (RR= 2.32).

Conclusion: Using he largest available real-life registry of longitudinally collected data on SSc, we demonstrated for the first time that smoking increases the risk for mortality in male SSc patients, but not in female SSc patients. Our results indicate that smoking partially explains the excess mortality observed in male SSc patients.

Table 1. Baseline characteristics of EUSTAR cohort patients included in the analysis.
Legend: DLCO: diffusing capacity of the lungs for carbon monoxide; FVC: forced vital capacity; IQR: interquartile range; SD: standard deviation. Disease duration was defined since the date of onset of Raynaud’s phenomenon.

Figure 2. Kaplan–Meier curves showing survival rate of ever-smokers and never-smokers in the whole EUSTAR cohort.

Figure 2. Kaplan–Meier curves of ever-smokers and never-smokers showing survival rate in male and female SSc patients.

Disclosures: J. Ciaffi: AbbVie/Abbott, 6, Amgen, 6, Boehringer-Ingelheim, 2, Janssen, 1, Novartis, 6; S. Liem: None; S. Ahmed: Janssen, 5; E. Hoekstra: None; P. Wiland: None; T. Atsuma: AbbVie, 5, 6, Alexion, 5, 6, Astellas, 5, 6, Boehringer-Ingelheim, 2, Bristol-Myers Squibb, 6, Chugai, 5, 6, Daiichi Sankyo, 5, 6, Eisai, 5, 6, Eli Lilly, 5, 6, Gilead, 5, 6, GSK, 2, 5, Merck Sharp & Dohme, 2, 6, Mitsubishi Tanabe Pharma, 5, 6, Otsuka, 5, 6, Pfizer, 5, 6, Sanofi/Genzyme, 2, 6, Takeda, 5, 6, UCB, 5, 6; G. Szucs: None; A. Balbir-Gurman: None; L. Czirjak: Abbvie, AstraZeneca, Boehringer Ingelheim, MSD, 6, Roche, 6; E. Zanatta: None; I. Koetter: None; J. Henes: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, GlaxoSmithKlein(GSK), 2, 6, Janssen, 2, 6, Novartis, 2, 6, Pfizer, 2, 6, UCB, 2, 6; m. Matucci Cerinic: accelerong, 2, 6, actelion, 2, 6, bayer, 2, 6, biogen, 2, 6, Boehringer-Ingelheim, 2, 6, Chemomab, 2, 6, corbus, 2, 6, CSL Behring, 2, 6, Eli Lilly, 2, 6, galapagos, 2, 6, Inventiva, 2, 6, Janssen, 2, 6, Merck/MSD, 2, 6, Mitsubishi, 2, 6, Pfizer, 2, 6, regeneron, 2, 6, Roche, 2, 6, samsung, 2, 6; P. Airò: Boehringer-Ingelheim, 2, 5, 6, Bristol-Myers Squibb(BMS), 2, 5, 6, CSL Behring, 2, 5, 6, Janssen-Cilag, 2, 5, 6, Novartis, 2, 5, 6, Roche, 2, 5, 6; F. Ursini: AbbVie/Abbott, 6, Gilead, 6, Pfizer, 6; T. Huizinga: None; J. de Vries-Bouwstra: AbbVie/Abbott, 2, 6, Boehringer-Ingelheim, 2, 6, galapagos, 5, Janssen, 2, 6, Janssen-Cilag, 5, Roche, 5.

To cite this abstract in AMA style:

Ciaffi J, Liem S, Ahmed S, Hoekstra E, Wiland P, Atsuma T, Szucs G, Balbir-Gurman A, Czirjak L, Zanatta E, Koetter I, Henes J, Matucci Cerinic m, Airò P, Ursini F, Huizinga T, de Vries-Bouwstra J. Cigarette Smoking Increases the Risk of All-Cause Mortality in Male Patients with Systemic Sclerosis: An Analysis of the EUSTAR Cohort [abstract]. Arthritis Rheumatol. 2023; 75 (suppl 9). https://acrabstracts.org/abstract/cigarette-smoking-increases-the-risk-of-all-cause-mortality-in-male-patients-with-systemic-sclerosis-an-analysis-of-the-eustar-cohort/. Accessed .

« Back to ACR Convergence 2023

ACR Meeting Abstracts - https://acrabstracts.org/abstract/cigarette-smoking-increases-the-risk-of-all-cause-mortality-in-male-patients-with-systemic-sclerosis-an-analysis-of-the-eustar-cohort/