Upadacitinib Safe for Atopic Dermatitis up to 7 Years in Pooled Analysis Findings

Long-term use of upadacitinib (UPA) over 7 years among patients with moderate-to-severe atopic dermatitis is safe, new data suggest.1

This conclusion regarding UPA’s safety in atopic dermatitis was the result of a recent pooled analysis presented at the 2026 Maui Derm Hawaii conference. Emma Guttman, MD, PhD, the system chair of the Department of Dermatology and Waldman professor of dermatology and immunology at the Icahn School of Medicine, led a team of investigators in authoring these data.

The poster was titled ‘Long-Term Upadacitinib Safety in Moderate‑to‑Severe Atopic Dermatitis up to 7 Years: An Integrated Analysis With Over 9600 Patient‑Years of Exposure.’ In its background section, Guttman et al noted the importance of treatments for atopic dermatitis not only for meaningful skin clearance and pruritus relief but also to maintain an acceptable safety profile in the long-term.

UPA, designed as an oral, reversible, selective Janus Kinase (JAK) inhibitor, was previously evaluated in the phase 3 Measure Up 1 (NCT03569293), Measure Up 2 (NCT03607422), and AD Up (NCT03568318) trials. The medication demonstrated significantly greater efficacy than placebo, along with a favorable risk-benefit balance among adolescent and adult populations with this skin disease.

Those on UPA reported durable improvements in skin pain, itch, and clearance of their disease extending through 188 weeks, with previous investigators pointing to safety data supporting utilization of UPA for as long as 6 years. In their current analysis, Guttman and colleagues pooled data from these 3 randomized, double-blind, multi-center, placebo-controlled phase 3 studies to evaluate longer-term use of UPA.

Adolescents aged 12 - 17 years and adults aged 18 - 75 years with moderate-to-severe disease were included. Moderate-to-severe atopic dermatitis was defined by by the investigative team as body involvement of at least 10% body surface area, a validated Investigator’s Global Assessment (IGA) score of 3 or greater, an Eczema Area and Severity Index score of 16 or higher, and a weekly average Worst Pruritus Numerical Rating Scale score of 4 at minimum.

Those recruited had been randomized in a 1:1:1 ratio to receive once-per-day oral UPA 15 mg, 30 mg, or placebo. During the Measure Up 1 and Measure Up 2 studies, the drug was administered without concomitant topical corticosteroids. However, in AD Up, they were permitted to implement background topical corticosteroids. After the initial 16-week double-blind period, those involved were originally assigned to UPA continued their respective doses in the blinded extension phase.

Those initially receiving placebo were re-randomized 1:1 to either UPA 15 mg or 30 mg, with treatment continuation permitted through Week 524.

Guttman et al’s integrated safety population was made up of 2683 subjects who were given at least a single dose of UPA, including 1337 patients on UPA 15 mg and 1346 on UPA 30 mg. A substantial proportion were shown to have baseline comorbidities and risk factors. The presence of cardiovascular risk factors was observed by the invesrtigators in 54.1% of those on the 15 mg dose and 51.3% of those on the 30 mg dose. Obesity, defined as a body mass index of 30 kg/m² or higher, was noted amng 18.9% and 19.3% of subjects, respectively. Previous vaccination against herpes zoster was shown by the team to be uncommon, with occurrences seen in no more than 5% of those included in either cohort (3.8% with 15 mg; 4.5% with 30 mg).

With up to 7 years of UPA exposure, Guttman and coauthors found overall rates of treatment-emergent adverse events (TEAEs), serious AEs, and AEs leading to treatment cessation were generally comparable between the 2 dose groups. Fatal treatment-emergent adverse events were noted to be rare. Specifically, rates were 0.1 events per 100 patient-years in both the UPA 15 mg and 30 mg arms. While overall TEAE rates were raised among those with UPA 30 mg, rates of serious AEs and discontinuations remained similar between dosing regimens.

Most of the AEs of special interest were sen at comparable frequencies across doses, though Guttman and colleagues found the exception was herpes zoster, which followed a known dose-dependent pattern. Slightly increased rates of serious and opportunistic infections were noted with UPA 30 mg versus UPA 15 mg. Eczema herpeticum accounted for most opportunistic infections. Notably, the investigators found incidence rates for malignancies excluding non-melanoma skin cancer, non-melanoma skin cancer, adjudicated major adverse cardiovascular events, and adjudicated venous thromboembolism remained low over long-term treatment. Specifically, rates were at or below 0.5 patients per 100 patient-years. These rates did not exceed background incidence levels reported in populations with atopic dermatitis.

“This integrated analysis of three phase 3 trials with over 9600 patient-years demonstrates consistently low rates of adverse events of special interest throughout 7 years of upadacitinib treatment,” Guttman and coauthors wrote.1

The study concluded AE rates between dosing regimens of UPA were generally comparable, without exceeding background incidence rates in the atopic dermatitis population. Such conclusions suggest a strong benefit-risk profile of UPA for those with moderate-to-severe disease, the team concluded.

References

1. Guttman E, Levy G, Bunick C, et al. Long-Term Upadacitinib Safety in Moderate‑to‑Severe Atopic Dermatitis up to 7 Years: An Integrated Analysis With Over 9600 Patient‑Years of Exposure. Presented at: Maui Derm Hawaii 2026; January 25-29, 2026; Maui, Hawaii.

2. Paller A, Mendes-Bastos P, Irvine A, et al. Upadacitinib in Adolescents With Moderate to Severe Atopic Dermatitis Analysis of 3 Phase 3 Randomized Clinical Trials Through 76 Weeks. JAMA Dermatol. Published online October 23, 2024. doi:10.1001/jamadermatol.2024.3696.