Rheumatoid Arthritis Linked to Elevated Pneumonia Risk, Especially in Seropositive Disease

Individuals living with rheumatoid arthritis (RA) face significantly higher risks of developing pneumonia and being hospitalized due to the infection, according to a study published in BMJ Open Respiratory Research.1

The analysis further revealed that serologic status and the type of disease-modifying antirheumatic drugs (DMARDs) used can influence susceptibility, underscoring the importance of infection prevention strategies in this patient population.

“Pneumococcal vaccination, as well as other viral vaccinations including influenza vaccination, might be an appropriate preventive strategy,” researchers said.

Higher Pneumonia Risk Across RA Cohorts

The nationwide cohort study drew on Korea’s National Health Insurance Service database, enrolling 41,187 individuals with RA and 205,935 matched controls between 2010 and 2017. After excluding patients with prior pneumonia, participants were followed for a median of 4.2 years.

Serologic status and DMARD type may influence susceptibility to infection. | Image credit: agenturfotografin – stock.adobe.com

During this period, RA was associated with a 73% higher adjusted risk of pneumonia (95% CI, 1.69-1.78) and a 126% higher risk of pneumonia-related hospitalization (95% CI, 2.15-2.37) compared with controls. A prior study looking at the link between RA and pneumonia reported a 68% increased risk of pneumonia and an 84% increased risk of pneumonia-related hospitalization in patients with RA compared with those without.2

Greatest Burden With Seropositive RA

The study stratified RA cases into seropositive RA (SPRA, n = 28,516) and seronegative RA (SNRA, n = 12,671).1 Both subgroups demonstrated higher risk than controls, but outcomes were notably worse in seropositive disease.

Patients with SPRA had an 86% higher risk of pneumonia (95% CI, 1.80-1.92) and a 152% higher risk of pneumonia-related hospitalization (95% CI, 2.39-2.65) compared with controls. Patients with SNRA also showed elevated risk, but to a lesser degree, with a 43% higher risk for pneumonia and 60% for hospitalization.

Compared with SNRA, SPRA was linked to a 29% higher risk of pneumonia and a 58% higher risk of hospitalization. Researchers noted that seropositivity may reflect greater systemic inflammation and disease severity, contributing to increased infection vulnerability.

“The reasons for the increased risk of pneumonia and pneumonia-related hospitalisation in SPRA compared with SNRA cannot be explained fully by our results because our study is observational,” the authors noted. “However, for the underlying mechanism of this observation, we suggest that SPRA has a stronger systemic inflammatory response to the more aggressive immunosuppressive treatments compared with SNRA.”

Medication-Specific Patterns of Risk

Researchers also examined how different DMARD classes affected pneumonia outcomes. Conventional synthetic DMARDs were associated with a 74% higher risk of pneumonia and a 122% higher risk of hospitalization

This trend persisted with biologic DMARDs. Patients using tumor necrosis factor inhibitors (TNFi) had a 75% higher risk of pneumonia and a 189% increased risk of hospitalization. The risk of pneumonia was slightly lower for those using non-TNFi biologics, increasing by 56%, but the hospitalization risk was highest for this group, increasing by 257%. Targeted synthetic DMARDs such as tofacitinib did not show a significantly increased risk of pneumonia (aHR, 0.93) or hospitalization (aHR, 1.21).

According to the authors, further studies should examine how disease activity, glucocorticoid use, and vaccination status intersect with pneumonia risk.

References

1. Moon SM, Han K, Jung JH, et al. Risk of pneumonia in individuals with rheumatoid arthritis: a nationwide cohort study. BMJ Open Respir Res. 2025;12(1):e002664. doi:10.1136/bmjresp-2024-002664
2. Doran MF, Crowson CS, Pond GR, O'Fallon WM, Gabriel SE. Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study. Arthritis Rheum. 2002;46(9):2287-2293. doi:10.1002/art.10524