Is it safe to start upadacitinib (Janus kinase inhibitor) in an elderly male with Giant Cell Arteritis (GCA)?

Starting Upadacitinib in an Elderly Male with Giant Cell Arteritis

Yes, upadacitinib 15 mg once daily can be started in an elderly male with GCA, as it demonstrated superior efficacy over placebo in achieving sustained remission (46.4% vs. 29.0%, P=0.002) while allowing for a shorter glucocorticoid taper, with no major adverse cardiovascular events observed in the pivotal trial. 1

Evidence Supporting Use in GCA

The SELECT-GCA phase 3 trial specifically evaluated upadacitinib in patients with giant cell arteritis and provides the strongest evidence for this indication 1:

• Upadacitinib 15 mg once daily achieved sustained remission at week 52 in 46.4% of patients compared to 29.0% with placebo (P=0.002) 1
• The trial included 70% of patients with new-onset GCA and 30% with relapsing disease 1
• Upadacitinib allowed for a 26-week glucocorticoid taper versus 52 weeks with placebo, significantly reducing cumulative steroid exposure 1
• The 7.5 mg dose was not superior to placebo and should not be used 1

Real-world data from multiple centers supports these findings 2, 3:

• In a 35-patient retrospective series, 57% achieved clinical remission and 46% achieved complete remission on JAK inhibitors (including upadacitinib), with median follow-up of 11 months 2
• Swedish data from 15 GCA patients showed significant CRP reductions at 3 months (p=0.02) and successful prednisolone tapering without relapses over mean 19-month exposure 3

Critical Safety Considerations in Elderly Patients

Cardiovascular Risk Assessment

The FDA boxed warning for upadacitinib is based on data from the ORAL Surveillance trial of tofacitinib in rheumatoid arthritis patients ≥50 years with cardiovascular risk factors, which showed increased rates of MACE, malignancy, and thromboembolism compared to TNF inhibitors 4, 5. However:

• No major adverse cardiovascular events occurred in either upadacitinib group during the 52-week SELECT-GCA trial 1
• Post-hoc analysis of upadacitinib 15 mg in RA patients at higher CV risk showed MACE, malignancy, and VTE rates were comparable to adalimumab 6
• The European Medicines Agency recommends caution in patients ≥65 years with CV risk factors but does not prohibit use when no suitable alternatives exist 4, 7

Age-Specific Considerations

Proceed with upadacitinib if:

• The patient requires glucocorticoid-sparing therapy due to steroid toxicity or inability to taper
• Alternative therapies (tocilizumab, methotrexate) have failed or are contraindicated 2
• Benefits of disease control outweigh theoretical CV risks, particularly given lack of MACE in the GCA trial 1

Exercise heightened caution if the patient has:

• Current or past smoking history 4
• History of cardiovascular disease (MI, stroke) 4
• Active malignancy or history of cancer 4
• History of venous thromboembolism 5

Infection Risk

The FDA label warns about serious infections, opportunistic infections, and tuberculosis reactivation 5:

• Screen for latent TB before initiating therapy and treat if positive 5
• Herpes zoster rates are elevated with upadacitinib versus comparators across all populations 6
• Serious infection rates were 11.7-12.4 events per 100 patient-years in long-term UC data 8
• Consider herpes zoster vaccination before starting therapy if not contraindicated 5

Dosing and Monitoring Protocol

Recommended Dosing

• Upadacitinib 15 mg once daily is the only effective dose for GCA 1
• Combine with a 26-week glucocorticoid taper as used in SELECT-GCA 1
• Do not use the 7.5 mg dose, as it showed no superiority over placebo 1

Monitoring Requirements

Based on FDA labeling and clinical trial protocols 5, 8:

• Baseline: Complete blood count with differential, comprehensive metabolic panel, lipid panel, TB screening, hepatitis B/C screening 5
• Follow-up: CBC, CMP every 3 months; lipid panel at 1-2 months then every 6-12 months 7, 5
• Clinical assessment at each visit for signs of infection, cardiovascular symptoms, or thrombosis 7, 5
• Interrupt therapy if serious or opportunistic infection develops until controlled 5

Common Pitfalls to Avoid

• Do not use the 7.5 mg dose - it was ineffective in the phase 3 trial 1
• Do not withhold therapy solely based on age - the SELECT-GCA trial included elderly patients and showed favorable outcomes 1
• Do not ignore CV risk factors - optimize blood pressure, lipids, and encourage smoking cessation before and during treatment 7
• Do not skip TB screening - latent TB must be identified and treated before starting upadacitinib 5
• Do not continue if thrombotic event occurs - discontinue immediately and evaluate 5