Rheumatoid Arthritis Linked to Greater Depression Risk in South Korea

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New data reveals both seropositive rheumatoid arthritis (RA) and seronegative RA are associated with a greater risk of depression.¹

“To the best of our knowledge, the current study is the first investigation to find an association between RA and subsequent depression risk based on RA seropositivity,” wrote investigators, led by Keun Hye Jeon, MD, from the department of family medicine at CHA Gumi Medical Center, CHA University School of Medicine, in the Republic of Korea.

Individuals with RA have a greater prevalence of depression, ranging from 14.8% - 22.5%, which is 2 – 3 times greater than the general population.² Depression alongside RA is associated with increased pain and disease activity, increased risk of incident myocardial infarction, poor health quality-of-life, less frequent remission, and greater use of health care services.¹

Despite depression being common for people with RA, a lack of research evaluating the association between RA seropositivity and biologic agents with depression risk existed. Thus, investigators conducted a retrospective cohort study of 38,478 patients with RA and 192,435 controls in South Korea to assess the risk of depression among recently diagnosed RA patients.

Participants were followed from 1 year after RA diagnosis or the corresponding index date to either the date of depression diagnosis, death, or the end of the follow-up period on December 31, 2019—whichever arrived first. The endpoint was newly diagnosed depression.

Investigators excluded participants if they had a previous depression diagnosis or were diagnosed with depression within a year after the index data. Additionally, participants had a mean age of 54.6 years and the majority were female (71%).

Investigators matched RA patients with controls 1:5 by age, sex, and index date. They collected information about the participants from the Korean Health Insurance Service database. Participants were enrolled from 2010 – 2017 and were followed up until 2019; the team analyzed the data in May 2023.

The team defined seropositive RA 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. Additionally, seronegative RA was defined with ICD-10 CODES M06 (not including MO6.1 and M06.4) and a prescription of any disease-modifying antirheumatic drugs for ≥ 270 days.

After a median follow-up of 4.1 years (2.4 – 6.2), 27,063 participants—6422 with RA and 20,641 controls—developed depression. Investigators found participants with RA had a 1.66-fold greater risk of depression compared to controls (adjusted hazard ratio [aHR], 1.66; 95% CI, 1.61 – 1.71). Both the seropositive RA group (aHR, 1.64; 95% CI, 1.58 – 1.69) and the seronegative RA group (aHR, 1.73; 95% CI, 1.65 – 1.81) were linked to an increased depression risk compared to controls.

When the team used the SNRA group as a reference group, the risk for depression in the SPRA group was 0.96 (95% CI, 0.91 – 1.01).

Furthermore, patients with RA who used biologic or targeted synthetic disease-modifying antirheumatic drugs (aHR, 1.33; 95% CI, 1.20 – 1.47) had a lower risk of depression compared with RA patients who did not take these medicines (aHR, 1.69; 95% CI, 1.64 – 1.74).

After adjusting for demographic characteristics, the team found no significant association between RA with age, gender, and behavioral factors.

“Given the female predominance in RA, male patients remain largely underrepresented and understudied, with comparatively smaller sample sizes,” investigators wrote. “Our study included a substantial number of male RA patients (n = 11 166) and provides strong evidence to support our findings.”

Investigators highlighted limitations, including limited data on RA disease activity preventing them from assessing RA severity and the level of depression, as well as not adjusting for potential confounders of social and family support. Additionally, participants came from health screenings, and thus could have been healthier and adopted healthier lifestyles than the general population.

“This nationwide cohort study found a strong association between RA and an increased risk of depression, regardless of age, sex, behavioral factors, and RA serologic status,” investigators concluded. “Therefore, clinicians should consistently screen all RA patients for depression and provide comprehensive health care that addresses both mental and physical well-being.”

^References

1. ^{Jeon KH, Han K, Jung J, et al. Rheumatoid Arthritis and Risk of Depression in South Korea. JAMA Netw Open. 2024;7(3):e241139. Published 2024 Mar 4. doi:10.1001/jamanetworkopen.2024.1139}
2. ^{Pine, L. Depression Prevalence in Patients with Rheumatoid Arthritis. HCPLive. September 22, 2021. https://www.hcplive.com/view/depression-prevalence-in-patients-with-rheumatoid-arthritis. Accessed March 11, 2024.}