Upadacitinib Led to Sustained, 140-Week Improvements for Atopic Dermatitis Patients

Individuals with moderate-to-severe atopic dermatitis may see continuous improvement in their skin symptoms and overall condition through 140 weeks of treatment with upadacitinib, according to recent findings, with better long-term patient-reported outcome (PRO) improvements observed among those given 30 mg versus 15 mg.¹

These late-breaking data were presented at the 2024 Revolutionizing Atopic Dermatitis (RAD) Annual Meeting in Chicago, Illinois. The study, led by Vimal H. Prajapati, a clinical associate professor at the University of Calgary, was conducted to examine the impact of upadacitinib as a monotherapy for moderate-to-severe atopic dermatitis patients’ skin conditions and PROs over a period of 140 weeks.

Prajapati and colleagues noted that the condition is a long-lasting, recurring inflammatory disease driven by patients’ immune systems and resulting in skin pain, pruritus, and disrupted sleep. Therefore, the team’s assessment considered ymptoms and their impact on quality of life (QoL).

Upadacitinib is an oral selective Janus kinase (JAK) inhibitor which has been approved by the US Food and Drug Administration (FDA) for treatment of moderate-to-severe eczema, referred to interchangeably here as atopic dermatitis. These trials had been previously covered in an interview featured in the coverage of the 2024 American Academy of Dermatology (AAD) Annual Meeting.²

Measure Up 1 and 2 Design

The investigators’ findings were drawn from the Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) studies, 2 parallel, multicenter, phase 3 trials which evaluated once-per-day oral upadacitinib in adolescents in the age range of 12–17 years as well as adults at or over 18 years of age.¹

Participants were randomly assigned in a 1:1:1 ratio to receive upadacitinib 15 mg, upadacitinib 30 mg, or a placebo at the start of the study. This analysis included data from patients in the upadacitinib 15 mg and 30 mg groups from both studies, with observations reported from week 16 (end of the double-blind period) to week 140 of the blinded extension period. Data for placebo recipients at week 16 were also included.

The investigators looked at measures assessing subjects’ eczema severity (Eczema Area and Severity Index [EASI]), life quality (Dermatology Life Quality Index [DLQI] for patients aged 16 and older, and Children’s DLQI [CDLQI] for those under 16), itch (Worst Pruritus Numerical Rating Scale [WP-NRS]), overall symptoms in their skin (ADerm-SS 7-item Total Symptom Score [TSS-7]), pain (AD Symptom Scale [ADerm-SS] Skin Pain), symptom severity (Patient-Oriented Eczema Measure [POEM]), and effect on sleep, daily activities, and emotional condition (AD Impact Scale [ADerm-IS]).

Findings

The research team looked at improvements from the point of baseline (WP-NRS, ADerm-SS Skin Pain, POEM improvements of ≥ 4; ADerm-SS TSS-7 improvement of ≥ 28; ADerm-IS Sleep, Daily Activities, and Emotional State improvements of ≥ 12, ≥ 14, and ≥ 11, respectively), minimal disease burden or impact (WP-NRS 0/1, ≥ 90% improvement from baseline in EASI [EASI 90], DLQI 0/1, CDLQI 0/1), as well as simultaneous EASI 90 and WP-NRS 0/1 achievement.

There were 1213 individuals included, with 603 being on upadacitinib 15 mg and 610 on upadacitinib 30 mg. The team noted that 19.9% were adolescents and 80.1% were adults.

At the 16-week mark, the investigators reported that meaningful improvements had been observed in participants’ PROs, with 36.7% and 53.1% of those on 15 mg and 30 mg, respectively, having WP-NRS 0/1. Additionally, 29.0% and 44.1% were able to achieve DLQI 0/1 as well as 23.5% and 50.0% with CDLQI 0/1, respectively.

These results were found by the team to be maintained or additionally enhanced through to the 140-week mark. By this point in time, the research team identified the proportions of subjects who had gotten clinically meaningful upadacitinib results among the 15 mg and 30 mg cohorts.

Specifically, the percentages were 74.6% and 81.5% for skin pain, 79.2% and 84.0% for daily activities, 64.8% and 70.9% for pruritus, 89.0% and 94.2% for skin symptom severity, 67.6% and 75.4% for skin symptoms, 76.5% and 84.0% for sleep, and 78.6% and 82.7% for emotional condition, respectively.

Rates identified by the team at the 140-week mark for the 15 mg and 30 mg arms of the trials were 67.3% and 75.6% for EASI 90, 45.1% and 51.4% for WP-NRS 0/1, 40.2% and 48.5% for DLQI 0/1, 40.5% and 47.1% for simultaneous EASI 90 and WP-NRS 0/1, and 35.7% and 65.0% for CDLQI 0/1, respectively.

References

1. ^{Prajapati V, Bunick C, Irvine A, et al. Sustained improvements over 140 weeks in signs, symptoms, and quality of life with upadacitinib in adolescents and adults with moderate-to-severe atopic dermatitis: integrated results from the phase 3 Measure Up 1 and Measure Up 2 studies. Revolutionizing Atopic Dermatitis (RAD) 2024 Annual Meeting June 8 – 10, 2024. Chicago, IL.}
2. ^{Smith T. Phase 3 Results on Upadacitinib for Atopic Dermatitis with Jonathan Silverberg, MD, PhD. HCPLive. March 8, 2024. https://www.hcplive.com/view/phase-3-results-on-upadacitinib-for-atopic-dermatitis-with-jonathan-silverberg-md-phd. Date accessed: June 13, 2024.}