Background/Purpose: The association between smoking and risk of rheumatoid arthritis (RA) has been well documented; however, the relationship between smoking and RA disease activity is less clear. Previous studies have indicated a null association between smoking and pain, swollen joint count, physical function, and radiographic joint damage, while others have demonstrated an inverse association. Inconsistent findings may be ascribed to heterogeneous study designs or biases in statistical analyses. We examined the causal association between smoking and RA outcomes using methods that account for time-varying confounding and loss to follow-up.

Methods: We used electronic health record data from a safety-net health system between 2013-2017. We included individuals with a diagnosis of RA and at least 2 clinic visits within 12 months (n=291). Timepoints during the study period were defined in 3-month intervals. We assessed smoking status (yes/no) at each timepoint; additional covariates included sex, race/ethnicity, age, obesity (BMI > 30 kg/m²), and medications. We also controlled for depression among a subset of patients (n=165) who had completed the Patient Health Questionnaire (PHQ-9). We used longitudinal targeted maximum likelihood estimation to estimate the causal effect of smoking on disease activity as measured by the clinical disease activity index (CDAI) and patient global assessment (PGA) at 30 months (or 2.5 years). We also accounted for time-varying covariates and informative missingness of data.

Results: Patients were 82% female, with a mean age 59.2 + 12.2 and 91% racial/ethnic minorities. Eleven percent of patients were smokers and the mean BMI was 29.0 + 6.9 (Table 1). Smoking was associated with a CDAI score of 16.67 at 30 months compared to a score of 12.05 for non-smoking after adjusting for covariates. Conversely, smoking was associated with a lower PGA score compared to non-smoking over the same period (40.53 vs. 45.42, respectively; p<0.001). However, additional control for depression based on the PHQ-9 did not change the association between smoking and disease activity based on CDAI (p<0.001), but eliminated the significant inverse relationship between smoking and PGA (p=0.24).

Conclusion: Smoking may be causally associated with higher levels of disease activity over time as measured by the CDAI. Differences in CDAI between smokers and non-smokers are likely clinically meaningful for individuals with low to moderate disease activity. Patient reported outcomes such as PGA may be influenced by other factors such as depression. These methods may be useful for investigations of additional exposures on longitudinal outcome measures in rheumatologic disease.

Table 1. Baseline characteristics of rheumatoid arthritis patients included in the study (n=291)

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/smoking-is-causally-associated-with-disease-activity-in-rheumatoid-arthritis/