Background/Purpose: Electronic cigarettes, or e-cigarettes, are inhalable aerosol nicotine-delivery devices increasingly used in addition or in place of cigarettes. Cigarette smoking is strongly associated with an at least ~1.5-fold increased risk of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The association of e-cigarettes with RA and SLE risk has not been well studied, however. We investigated e-cigarette use and risks of developing RA or SLE in a nationwide US cohort.

Methods: We used data from the All of Us Research Program (version 8), comprised of >393,000 U.S. adults with linked electronic health records. Using a matched cohort design, we identified participants with baseline self-reported ever use of e-cigarettes, including electronic nicotine products such as vape pens and hookah pens. We created a cohort matched on age, sex at birth, race/ethnicity, enrollment year, and cigarette smoking status, without any e-cigarette use. The primary outcome was RA or SLE, identified by ≥ 2 ICD9, ICD10, or SNOMED codes. After excluding those with RA or SLE pre-enrollment, individuals were followed from enrollment until 1st occurrence of RA or SLE, death, end of study period (October 1, 2023), or up to 5 years, whichever occurred first. We estimated incidence rates (IRs) and an incidence rate ratio (IRR) and plotted the cumulative incidence curves. Stratified and interaction analyses by cigarette smoking status were performed.

Results: We identified 60,285 e-cigarette users and 60,285 matched non-users (Table 1). The mean age was 40 (SD 14) years and 40% were male; 65% were ever smokers. A total of 271 cases developed among e-cigarette users in 182,978 person-years (IR 1.48 [95% CI 1.31-1.67]) vs 239 incident cases among matched non-users in 186,127 person-years (IR 1.28, 95% CI 1.13-1.46; IRR 1.15 [95% CI: 0.97-1.37]). E-cigarette users had a not statistically significant higher risk of RA or SLE (p 0.1, Figure 1). In analyses stratified by smoking status, a similar trend was observed among smokers, while the risk of RA or SLE was comparable between e-cigarette users and non-users among non-smokers (Figure 2). No statistically significant interaction according to smoking status was observed on either the additive or multiplicative scale.

Conclusion: Our findings suggest that e-cigarette users may have a slightly higher risk of developing RA or SLE vs. non-users, especially in smokers. Key considerations in interpreting these results include that a substantial proportion of e-cigarette users were smokers, a known risk factors for RA and SLE itself and the intensity of smoking and e-cigarette use were not well captured by the survey. E-cigarette users were also younger, although we matched by age to limit age-related bias. Further studies are warranted, particularly those assessing the amount, frequency, or duration of e-cigarette use.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/electronic-cigarette-use-in-association-with-risks-of-developing-rheumatoid-arthritis-or-systemic-lupus-erythematosus-in-the-all-of-us-research-program/