Frailty and Cardiovascular Safety of JAK Inhibitors versus TNF Inhibitors in Rheumatoid Arthritis

Strategic Insights -

Research conducted at the University of Ferrara has shed light on the risk of cardiovascular events (CVEs) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) or tumor necrosis factor inhibitors (TNFis). The study aimed to compare the risk of CVEs in RA patients treated with JAKis or TNFis, while also exploring the interactions with patient profiles, including age, baseline cardiovascular risk, and frailty. The researchers used a retrospective study based on healthcare administrative databases (AHDs) of the Lombardy region, Italy, covering the period from January 1, 2020, to December 31, 2023.

Key Takeaways:

  • The study identified 7,541 therapeutic courses in 5,563 patients, with 2,343 patients starting as TNFi users, 1,443 as JAKi users, and 1,777 starting with other drugs (1,459 days of follow-up).
  • The crude incidence rates for new CVEs were 16.6 and 18.6 per 1,000 person-years for TNFi and JAKi users, respectively.
  • Exposure to JAKis was not associated with a significantly increased risk of CVEs, MACEs, or TEs compared to TNFis, with adjusted hazard ratios of 0.92, 0.71, and 1.53, respectively.
  • Each 0.1-point increment of the frailty index significantly increased the hazard ratio for new CVEs, MACEs, and TEs.
  • The interaction between the period of drug delivery and the treatment with JAKis on the risk of new CVEs was not significant, while the interaction with baseline cardiovascular risk was statistically significant.

Statistics:

  • 7,541 therapeutic courses in 5,563 patients were identified in the study.
  • The crude incidence rates for new CVEs were 16.6 and 18.6 per 1,000 person-years for TNFi and JAKi users, respectively.
  • Adjusted hazard ratios for exposure to JAKis were 0.92 for CVEs, 0.71 for MACEs, and 1.53 for TEs.
  • The frailty index increased the hazard ratio for new CVEs by 180% (HR: 1.80, 95% CI: 1.48-2.19), MACEs by 66% (HR: 1.66, 95% CI: 1.10-2.51), and TEs by 69% (HR: 1.69, 95% CI: 1.03-2.78).

Sources:

  • Frailty and cardiovascular safety of JAK inhibitors versus TNF inhibitors in rheumatoid arthritis: a real-world comparative study of drug effects and patient profiles. Frontiers in Pharmacology, 2025,16.
  • http://journal.frontiersin.org/journal/pharmacology
  • Frontiers Media S.A.