In both studies, a higher proportion of patients on upadacitinib 15 mg and 30 mg achieved EASI-75, EASI-90, and EASI-100 compared with the placebo groups.
Twin Phase 3 studies show that upadacitinib has great therapeutic potential for moderate to severe atopic dermatitis.
Measure Up 1 and Measure Up 2, replicate multicenter, randomized, double-blind, placebo-controlled trials, evaluated the safety and efficacy of the Janus Kinase (JAK) inhibitor as monotherapy in both adult and adolescent populations.
"When patients are on a systemic, they tend to leave old topicals behind," lead investigator Emma Guttman-Yassky, MD, PhD, of Icahn School of Medicine at Mount Sinai, told HCPLive®. She noted the inconvenience of combination and/or topical regimens for these patients.
As such, both trials demonstrated that upadacitinib as monotherapy was associated with high rates of clearance and improvements in clinical measures of disease.
About the Studies
In the Measure Up 1 trial, the investigators enrolled patients across 151 clinical centers and 24 countries. The Measure 2 trial enrolled patients from 154 centers across 23 countries.
Across both trials, the patient population age ranged from 12 – 75 years. All individiauls presented with moderate-to-severe atopic dermatitis—indicated by ≥10% of affected body surface area, Eczema Area and Severity Index [EASI] score ≥16 and validated Investigator’s Global Assessment for Atopic Dermatitis [vIGA-AD] score ≥3.
All patients (Measure Up 1, n = 847; Measure Up 2, n = 836) were randomly assigned 1:1:1 to upadacitinib 15 mg, 30 mg, or placebo once daily for 16 weeks.
The primary endpoints included the proportion of patients achieving ≥75% improvement in EASI score from baseline (EASI75) as well as the proportion of patients who achieved a vIGA-AD response, defined as a vIGA-AD score of 0 or 1 with ≥2 grades of reduction from baseline, at week 16.
Efficacy and safety were assessed at follow-up visits at weeks 1, 2, 4, 8, 12, 16, and beyond.
Guttman-Yassky and team reported that the co-primary endpoints were met in both studies (all P<.0001).
In Measure Up 1, a significantly higher proportion patients in the upadacitinib 15 mg (70% of 281 patients) and upadacitinib 30 mg (80% of 285) groups achieved EASI-75 compared with the placebo group (16% of 281; upadacitinib 15 mg response rate [RR], 53.3% [95% CI, 46.4-60.2]; upadacitinib 30 mg RR, 63.4% [95% CI, 57.1-69.8]).
The investigators noted a similar result for Measure Up 2, showing the superiority of upadacitinib 15 mg (60% of 276 patients) and 30 mg (73% of 282) over placebo (13% of 278) in inducing EASI-75 responses (upadacitinib 15 mg RR, 46.9% [95% CI, 39.9-53.9]; upadacitinib 30 mg RR, 59.6% [95% CI, 53.1-66.2]).
“In both studies, a higher proportion of patients in the upadacitinib 15 mg and 30 mg groups achieved EASI-90 and EASI-100 responses at week 16 than in the placebo group (all P<.0001),” the team added.
Additionally, in both trials, a greater proportion of upadacitinib-treated patients for both doses achieved vIGA-AD response compared placebo.
In Measure Up 1, these proportions were 48% for upadacitinib 15 mg, 62% for 30 mg, and 8% for placebo (upadacitinib 15 mg RR, 39.8% [95% CI, 33.2-46.4]; upadacitinib 30 mg RR, 53.6% [95% CI, 47.2-60.0]).
In Measure Up 2, they were 39% for upadacitinib 15 mg, 52% for 30 mg, and 5% for placebo (upadacitinib 15 mg RR, 34.0% [95% CI, 27.8-40.2]; upadacitinib 30 mg RR, 47.4% [95% CI, 41.0-53.7]).
As for safety, the both doses of the JAK inhibitor were considered well-tolerated across the patient population, with similar incidences of serious adverse events and adverse events leading to drug discontinuation among the groups.
The most common treatment-emergent adverse events were acne, upper respiratory tract infection, nasopharyngitis, headache, elevation in creatine phosphokinase levels, and atopic dermatitis.
"This enriches our toolobox for atopic dermatitis with an oral systemic," Guttman-Yassky said. "Upadacitinib will be one of the first orals approved for this disease. With the other 2 JAKS [seeking approval], we'll likely have 3 new medications in the summer."
The study, “Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials,” was published online in The Lancet.