Long-term Upadacitinib Data Show Low Rates of MACE, Malignancy

Key Takeaways

• Upadacitinib demonstrated a stable safety profile over 6 years in patient groups of multiple agew with moderate-to-severe atopic dermatitis (AD), according to a new study presented at AAD 2026.
• Exposure-adjusted rates of serious adverse events remained low, though higher rates were observed in patients ≥65 years, particularly with 30 mg dosing.
• Herpes zoster showed a dose-dependent increase, while rates of malignancy, MACE, and VTE remained low and generally similar between doses.

Long-term safety data from three phase 3 trials (Measure Up 1, Measure Up 2, and AD Up) provided a 6-year view of upadacitinib in moderate-to-severe atopic dermatitis (AD) stratified across multiple age groups.

A total of 2,683 patients in the analysis received at least one dose (UPA 15 mg, n = 1337; UPA 30 mg, n = 1346), representing 9187.7 patient-years of exposure globally.

Exposure-adjusted event rates remained low across age groups. Serious infections occurred at rates of 2.2 and 2.6 events per 100 patient-years (E/100 PY) for UPA 15 mg and 30 mg, respectively. Herpes zoster rates were higher with the 30 mg dose (5.2 vs 3.2 E/100 PY), demonstrating a dose-dependent trend. Opportunistic infections were infrequent (1.6–2.0 E/100 PY), with eczema herpeticum among the most reported.

Malignancy rates excluding nonmelanoma skin cancer (0.3 vs 0.5 E/100 PY), nonmelanoma skin cancer (0.4 vs 0.4 E/100 PY), major adverse cardiovascular events (0.2 vs <0.1 E/100 PY), and venous thromboembolism (0.1 vs 0.1 E/100 PY) were low and generally comparable between dose groups. Notably, no MACE events were reported in patients aged 12–49 years.

Age-stratified findings showed higher adverse event rates among patients ≥65 years, particularly with UPA 30 mg (eg, serious infections up to 5.7 E/100 PY), while rates were largely similar across doses in patients <65 years. No active tuberculosis cases were observed outside a very low frequency in adults aged 18–49 years.

“Based on the integrated analysis of long-term safety data for up to 6 years, rates of adverse events of special interest were low for UPA 15 mg and UPA 30 mg in patients with moderate-to-severe atopic dermatitis,” the authors wrote. "These findings support the use of UPA across all approved ages in moderate-to-severe AD, with UPA15 remaining the dose of choice in patients ≥65 years to optimize safety."

Source: Bunick CG; Irvine AD, Lio P, Eyerich K, Lima H, DPrefontaine D, Levy G, Dilley D, Grada A, Silverberg JI. Long-Term 6-Year Safety of Upadacitinib in Moderate-to-Severe Atopic Dermatitis Across Ages: Results From Three Phase 3 Studies. Poster 75678. Presented at: American Academy of Dermatology Annual Meeting; March 27-31, 2026; Denver.