Upadacitinib Sustained Efficacy, Safety Among Patients with Atopic Dermatitis Over 188 Weeks

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Upadacitinib treatment leads to sustained itch reduction, skin clearance, and consistent safety through 188 weeks among adolescents and adults with moderate-to-severe atopic dermatitis, according to recent findings.¹

These data were the conclusion of a recent interim analysis of the ongoing phase 3 studies known as Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422). The abstract in which this data was included was titled ‘Efficacy and Safety of Upadacitinib Through 188 Weeks in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial’ and presented during the Revolutionizing Atopic Dermatitis Conference Mid-Year Virtual Update on December 8, 2024.

The Measure Up 1 and 2 studies of upadacitinib, an oral Janus kinase 1 (JAK1) inhibitor, was previously approved by the US Food and Drug Administration (FDA) and in other countries for treating moderate-to-severe atopic dermatitis.² This integrated analysis, led by Alan D. Irvine MD, DSc, assessed the medication’s long-term efficacy and safety over 188 weeks.

Design Details

Both the Measure Up 1 and Measure Up 2 analyses were randomized, double-blinded, and multi-center in their design. Those who decided to participate in these 2 studies were aged 12 - 75 years and had been diagnosed with moderate-to-severe atopic dermatitis.

The subjects were randomized into 3 groups initially, with each being given an administratoion of upadacitinib 15 mg (UPA15), upadacitinib 30 mg (UPA30), or a placebo on a basis of once-per-day. Those featured in the upadacitinib cohorts, following a period of 16 weeks, continued to be given their respective dosages.

Meanwhile, the investigative teams of these studies re-randomized the participants who had initially been assigned to the placebo cohort. Specifically, they were all split into those receiving either UPA15 or UPA30.

The teams assessed several key outcomes at the 16-week mark. Specifically, they looked at participants who achieved at least a 75% reduction in their EASI scores (EASI 75) as well as those with a vIGA-AD score labeled as 'clear' (0) or 'almost clear' (1).

For the latter outcome, the investigators noted those who had a reduction of at least 2 grades from the point of baseline (vIGA-AD 0/1). Additionally, the research team evaluated any improvements in pruritus, also known as itch, and these improvements included a ≥4-point reduction on the Worst Pruritus Numeric Rating Scale (WP-NRS) as well as combined endpoints such as WP-NRS 0/1 and EASI 90.

The team heading the interim analysis looked at efficacy outcomes and summarized them using observed cases (OC). This suggests that all treatment-period data were considered by them.

The evaluations of safety included monitoring serious adverse events (SAEs), monitoring treatment-emergent adverse events (TEAEs), and monitoring any adverse events of special interest (AESIs). They calculated these as exposure-adjusted rates per 100 patient-years.

Findings on Upadacitinib

When looking at the studies' efficacy findings, the investigators identified several sustained improvements through to the 188-week mark. By this point, 86.3% of those in the UPA15 arm and 89.0% of those in the UPA30 arm successfully achieved EASI 75.

They noted, however, that only 59.5% and 61.8% reached vIGA-AD 0/1, respectively. The team found that there was a ≥4 point reduction in WP-NRS seen among 63.8% of those given UPA15 and 68.7% of those given UPA30.

Additionally, 41.1% of those in the UPA15 group and 41.3% of those in the UPA30 group were shown by the investigators to have met the combined endpoint of EASI 90 and WP-NRS 0/1.

After assessing safety, the researchers determined that findings were consistent with earlier analyses. They also noted that the known safety profile of the medication was consistent, with both dosages shown to be well-tolerated.

In terms of commonly-observed adverse events, notable examples included COVID-19 infections, nasopharyngitis, acne, atopic dermatitis, upper respiratory tract infections, increased blood CPK, and cases of oral herpes. Data included from the 188-week period within these pivotal studies were noted in the abstract as covered in greater detail at the time of presentation.

“In this interim analysis, sustained skin clearance, itch reduction, and a consistent safety profile were observed with upadacitinib 15 mg and UPA 30 mg through 188 weeks in adolescent and adult patients with moderate-to-severe [atopic dermatitis],” they wrote.¹

References

1. ^{Irvine A, Silverberg J, Pechonkina A, et al. Efficacy and Safety of Upadacitinib Through 188 Weeks in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis: Phase 3 Randomized Clinical Trial Results. Presented as part of the 2024 Revolutionizing Atopic Dermatitis Mid-Year Virtual Update. December 8, 2024.}
2. ^{Butera A. FDA Approves Upadacitinib for Patients 12 Years and Older with Moderate to Severe Atopic Dermatitis. January 14, 2022. https://www.hcplive.com/view/fda-upadacitinib-children-atopic-dermatitis. Date accessed: December 13, 2024.}