Upadacitinib Safety Considerations in Older Adults

Introduction to Safety Risks

The European Medicines Agency recommends using tofacitinib (and by extension, JAK inhibitors as a class) in patients with rheumatoid arthritis "above the age of 65 only when there is no alternative treatment" 2
The American Gastroenterological Association suggests cautious use of JAK inhibitors in patients at high risk of major adverse cardiovascular events, such as those with prior cardiovascular disease, current or past smoking, hypertension, diabetes, or a family history of premature coronary disease 4

Upadacitinib should only be prescribed for patients aged ≥65 years when no suitable alternatives exist, due to increased risk of major cardiovascular events, serious infections, and malignancy 1
Patients aged ≥50 years with cardiovascular risk factors should not receive JAK inhibitors as first-line therapy when TNF inhibitors remain an option 4, 1

Age is a major independent risk factor for venous thromboembolism (VTE) with JAK inhibitors, with patients older than 65 years at higher risk 3
The risk of VTE may be up to 10-fold for patients with a history of VTE and twofold for those taking COX-2 inhibitors 2
Patients aged ≥50 years with cardiovascular risk factors require cautious use of JAK inhibitors 4

If TNF inhibitors, IL-23 inhibitors, or other biologics are viable options, these should be prioritized over upadacitinib in older patients 4, 1
If ≥1 cardiovascular risk factor is present in addition to age ≥78 years, alternative treatments are strongly preferred 4, 1

Laboratory monitoring, including CBC with differential and comprehensive metabolic panel, should be performed at baseline, 4-8 weeks after starting, then every 3 months 6
Clinical monitoring should include signs of infection, particularly herpes zoster, and warning signs of VTE 6, 5

Do not use upadacitinib as first-line therapy in older patients when biologics are available and appropriate 4, 1, 7
Do not overlook the cumulative effect of multiple risk factors, which may make upadacitinib inappropriate even if no single absolute contraindication exists 2, 4, 3
Do not fail to vaccinate before starting therapy, as patients should receive recombinant zoster vaccine (Shingrix) before initiating treatment 6, 1