Safety of Janus Kinase Inhibitors in Older Patients: A Focus on the Thromboembolic Risk

Area of Science:

• Immunology
• Pharmacology
• Geriatrics

Background:

• The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway regulates gene transcription.
• JAK inhibitors are effective treatments for autoimmune conditions like rheumatoid arthritis.
• Concerns exist regarding increased infection risk, particularly varicella-zoster reactivation, with JAK inhibitor use.

Purpose of the Study:

• To review the adverse effects and risks associated with JAK inhibitors.
• To highlight the heightened risks in the older population due to comorbidities and altered pharmacokinetics.
• To emphasize the importance of understanding these risks for clinicians treating elderly patients.

Main Methods:

• Literature review and analysis of safety data.
• Examination of regulatory warnings from the US FDA and European Medicines Agency.
• Assessment of risk factors including age, comorbidities, and cardiovascular risk.

Main Results:

• JAK inhibitors are associated with an increased risk of infections and thromboembolic events (deep vein thrombosis, pulmonary embolism).
• Older patients (>50 years) with cardiovascular risk factors face a significantly elevated risk.
• Regulatory agencies have issued warnings, including a black box warning from the FDA, regarding these risks.

Conclusions:

• Clinicians must be aware of the serious adverse effects of JAK inhibitors, particularly in older adults.
• Careful patient selection and monitoring are crucial to mitigate risks like infection and thrombosis.
• Understanding pharmacokinetic changes and comorbidities in the elderly is essential for safe JAK inhibitor prescribing.