Rheumatoid Arthritis and Risk of Depression in South Korea.

Importance: Depression is among the most common comorbidities in rheumatoid arthritis (RA). There is a lack of data regarding the association of RA seropositivity and biologic agents with depression risk among individuals with RA. Objective: To investigate the risk of depression following RA diagnosis among patients in South Korea. Design, Setting, and Participants: This retrospective cohort study included 38 487 patients with RA and a comparison group of 192 435 individuals matched 1:5 for age, sex, and index date. Data were from the Korean National Health Insurance Service database. Participants were enrolled from 2010 to 2017 and were followed up until 2019. Participants who had previously been diagnosed with depression or were diagnosed with depression within 1 year after the index date were excluded. Statistical analysis was performed in May 2023. Exposures: Seropositive RA (SPRA) was defined with the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes M05 and enrollment in the Korean Rare and Intractable Diseases program. Seronegative RA (SNRA) was defined with ICD-10 codes M06 (excluding M06.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs (DMARDs) for 270 days or more. Main Outcomes and Measures: Newly diagnosed depression (ICD-10 codes F32 or F33). Results: The mean (SD) age of the total study population was 54.6 (12.1) years, and 163 926 individuals (71.0%) were female. During a median (IQR) follow-up of 4.1 (2.4-6.2) years, 27 063 participants (20 641 controls and 6422 with RA) developed depression. Participants with RA had a 1.66-fold higher risk of depression compared with controls (adjusted hazard ratio [aHR], 1.66 [95% CI, 1.61-1.71]). The SPRA group (aHR, 1.64 [95% CI, 1.58-1.69]) and the SNRA group (aHR, 1.73 [95% CI, 1.65-1.81]) were associated with an increased risk of depression compared with controls. Patients with RA who used biologic or targeted synthetic DMARDs (aHR, 1.33 [95% CI, 1.20-1.47]) had a lower risk of depression compared with patients with RA who did not use these medications (aHR, 1.69 [95% CI, 1.64-1.74]). Conclusions and Relevance: This nationwide cohort study found that both SPRA and SNRA were associated with a significantly higher risk of depression. These results suggest the importance of early screening and intervention for mental health in patients with RA.

Does Rheumatoid Arthritis Increase the Risk of COPD?: A Nationwide Retrospective Cohort Study.

BACKGROUND: Most reports of pulmonary manifestations in rheumatoid arthritis (RA) have been related to interstitial lung diseases. RA and COPD are both chronic inflammatory systemic diseases. RESEARCH QUESTION: Does RA increase the risk of developing COPD? Is there a difference between seropositive and seronegative RA in the risk of COPD? STUDY DESIGN AND METHODS: Using the Korean National Health Insurance Database, we screened individuals diagnosed with RA between 2010 and 2017. We identified 46,030 patients with RA (32,608 with seropositive RA and 13,422 with seronegative RA) and 230,150 matched control individuals; we monitored them until December 2019. We used multivariate Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) of risk factors for the development of COPD. RESULTS: The incidence of COPD among patients with RA was 5.04 per 1,000 person-years; it was 2.23 per 1,000 person-years in the control group. Patients with RA showed a higher risk of developing COPD (aHR, 2.11; 95% CI, 1.96-2.28) compared with the control group. Although both seropositive RA and seronegative RA were associated with an increased risk of COPD, patients with seropositive RA had a higher risk for the development of COPD (aHR, 1.26; 95% CI, 1.09-1.46) than patients with seronegative RA. In the subgroup analyses, smoking history did not demonstrate significant interactions between RA and COPD development. INTERPRETATION: RA was shown to be associated with an increased risk of COPD development, augmented by seropositivity. Physicians should monitor respiratory symptoms and pulmonary function carefully in patients with RA.

Rheumatoid Arthritis and Risk of Lung Cancer: A Nationwide Cohort Study.

INTRODUCTION: There has been an increasing interest in the risk of lung cancer related to rheumatoid arthritis (RA). We investigated the association between RA and the risk of lung cancer with consideration of key confounding factors, including RA serostatus and smoking status. METHODS: Using a nationwide database, we identified 51,899 patients with newly diagnosed RA between 2010 and 2017, which were matched by sex and age at a 1:5 ratio with 259,495 non-RA population. The association of lung cancer and RA was investigated using Cox regression analyses. Stratified analyses by smoking status, sex, age, and comorbidity of interstitial lung disease were conducted using the same Cox modeling. RESULTS: During 4.5 years of follow-up, the adjusted hazard ratio of lung cancer in the patients with RA was 1.49 (95% confidence interval: 1.34-1.66). Compared with the patients with seronegative RA, an increased risk of lung cancer was not considerable in the patients with seropositive RA. In the stratified analyses, the increased risk of lung cancer was more prominent in current or previous heavy smokers with RA (interaction p value of 0.046) and male patients (interaction p < 0.001), whereas there was no substantial effect associated with age or interstitial lung disease status. CONCLUSIONS: Patients with RA had an increased risk of lung cancer compared with the non-RA group, and the risk did not differ by RA serostatus. There is a need for increased awareness of smoking cessation and potentially for regular lung cancer screening with proper risk stratification in patients with RA.

Women with Metabolic Syndrome and Unhealthy Lifestyle Factors Are at a Higher Risk for Hyperuricemia.

Hyperuricemia (HUA) has become a significant medical concern due to its complications and links to metabolic syndrome (MetS) and cardiovascular disease (CVD), which result in increased mortality. The pathogenic processes associated with unhealthy behaviors, MetS, and HUA can be cooperative and potentially synergistic in the activation of risk factors. Recent research has shown sex-based differences in the relationship between HUA and its associated risk factors. This study aimed to investigate these differences, particularly in the context of MetS and CVD risk factors and unhealthy lifestyles. We also aimed to evaluate the joint effects of these factors based on sex. We conducted a cross-sectional study using nationally representative survey data from the Korean National Health and Nutritional Examination Survey 2016-2018. We performed multivariable logistic regression analysis, calculating adjusted odds ratios (ORs) with their 95% confidence intervals (CIs). We also conducted subgroup analyses based on sex and the presence of MetS with or without unhealthy lifestyle factors (tobacco use, alcohol intake). We found sex-based differences in the relationships between HUA and MetS, CVD risk factors, and lifestyle behaviors. Our major finding was a significant association between MetS and HUA in both men and women, regardless of alcohol consumption and smoking status, and this association was stronger in women. We also observed a synergistic effect of MetS and lifestyle factors on the risk of HUA, particularly in women, in whom the risk of HUA increased up to four times compared to the reference group. A sex-based clinical strategy for HUA is necessary to reduce related complications and their socio-economic burden.

Rheumatoid Arthritis and Risk of Parkinson Disease in Korea.

Importance: Although it has been postulated that chronic inflammation caused by rheumatoid arthritis (RA) contributes to the development of Parkinson disease (PD), the association between these 2 conditions has yet to be determined. Objective: To evaluate the association between RA and subsequent PD risk. Design, Setting, and Participants: This retrospective cohort study used the Korean National Health Insurance Service database to collect population-based, nationally representative data on patients with RA enrolled from 2010 to 2017 and followed up until 2019 (median follow-up, 4.3 [IQR, 2.6-6.4] years after a 1-year lag). A total of 119 788 patients who were first diagnosed with RA (83 064 with seropositive RA [SPRA], 36 724 with seronegative RA [SNRA]) were identified during the study period and included those who underwent a national health checkup within 2 years before the RA diagnosis date (64 457 patients). After applying exclusion criteria (eg, age <40 years, other rheumatic diseases, previous PD), 54 680 patients (39 010 with SPRA, 15 670 with SNRA) were included. A 1:5 age- and sex-matched control group of patients without RA was also included for a total control population of 273 400. Exposures: Rheumatoid arthritis as defined using International Classification of Diseases, Tenth Revision codes M05 for SPRA and M06 (except M06.1 and M06.4) for SNRA; prescription of any disease-modifying antirheumatic drug; and enrollment in the Korean Rare and Intractable Diseases program. Main Outcomes and Measures: The main outcome was newly diagnosed PD. Data were analyzed from May 10 through August 1, 2022, using Cox proportional hazards regression analyses. Results: From the 328 080 individuals analyzed (mean [SD] age, 58.6 [10.1] years; 74.9% female and 25.1% male), 1093 developed PD (803 controls and 290 with RA). Participants with RA had a 1.74-fold higher risk of PD vs controls (95% CI, 1.52-1.99). An increased risk of PD was found in patients with SPRA (adjusted hazard ratio [aHR], 1.95; 95% CI, 1.68-2.26) but not in patients with SNRA (aHR, 1.20; 95% CI, 0.91-1.57). Compared with the SNRA group, those with SPRA had a higher risk of PD (aHR, 1.61; 95% CI, 1.20-2.16). There was no significant interaction between covariates on risk of PD. Conclusions and Relevance: In this study, RA was associated with an increased risk of PD, and seropositivity of RA conferred an augmented risk of PD. The findings suggest that physicians should be aware of the elevated risk of PD in patients with RA and promptly refer patients to a neurologist at onset of early motor symptoms of PD without synovitis.