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Serious Infection Risk With TNF Inhibitors vs. JAK Inhibitors in Rheumatoid Arthritis: A Nationwide Claims-Based

Ryosuke Ota1, Atsushi Hirata1, Takeo Hata2,3

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Clinical Pharmacology and Therapeutics
|December 21, 2025
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This summary is machine-generated.

Tumor necrosis factor-α inhibitors (TNFαi) reduced serious infections in rheumatoid arthritis patients compared to Janus kinase inhibitors (JAKi). TNFαi are recommended for infection-prone populations, emphasizing personalized treatment decisions.

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Area of Science:

  • Rheumatology
  • Immunology
  • Pharmacology

Background:

  • Rheumatoid arthritis (RA) treatment involves biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).
  • Tumor necrosis factor-α inhibitors (TNFαi) and Janus kinase inhibitors (JAKi) are common RA therapies.
  • Comparing serious infection risks between TNFαi and JAKi is crucial for patient safety.

Purpose of the Study:

  • To compare the risk of serious infections in rheumatoid arthritis patients treated with TNFαi versus JAKi.
  • To evaluate the safety profile of TNFαi and JAKi concerning serious infections.

Main Methods:

  • Retrospective cohort study using a Japanese nationwide claims database.
  • Included new users of TNFαi or JAKi for rheumatoid arthritis (ICD-10 codes M05 or M06).
  • Propensity score overlap weighting was applied; serious infection was the primary outcome.

Main Results:

  • TNFαi use was associated with a significantly lower risk of serious infections compared to JAKi (HR: 0.55; 95% CI: 0.39-0.77).
  • Lower risks of respiratory tract infections, urogenital infections, and sepsis were observed with TNFαi.
  • Baricitinib and infliximab showed an elevated infection risk in drug-specific analyses.

Conclusions:

  • TNFαi use is linked to a lower risk of serious infections than JAKi in rheumatoid arthritis patients.
  • Findings support preferential use of TNFαi in infection-prone RA populations.
  • Individualized risk assessment is vital for RA treatment decisions.