Favorable Benefit-Risk Profile for Upadacitinib for the Long-Term Treatment of Atopic Dermatitis

A long-term follow-up of 2 randomized clinical trials found that upadacitinib had a favorable risk-benefit profile for the treatment of atopic dermatitis (AD). These study findings were published in JAMA Dermatology.

Long-term follow-up from the Measure Up 1 and Measure Up 2 trials, which were phase 3, multicenter, double-blind, placebo-controlled trials conducted in 151 and 154 centers, respectively were included in this interim analysis. In each trial, patients with AD aged 12 to 75 years were randomly assigned in a 1:1:1 ratio to receive 15 or 30 mg daily oral upadacitinib or placebo for 16 weeks. At week 16, the upadacitinib recipients continued their assigned treatment, and the placebo cohorts were rerandomized in a 1:1 ratio to receive 15 or 30 mg UPA. This study evaluated the safety and efficacy of upadacitinib up to December 2020 (Measure Up 1) or January 2021 (Measure Up 2).

Recipient groups of 15 mg (n=557), 30 mg (n=567), placebo and 15 mg (n=241), and placebo and 30 mg (n=244) upadacitinib  comprised 51.2% to56.0% women, 85.7% to86.5% were aged 18 years or older, 65.7% to 68.0% were White, mean disease duration was 19.6 to 21.3 years, and body surface area affected was 44.4% to 47.0%.

Patients who were randomly assigned to receive placebo had a similar trajectory after switching to upadacitinib  as the patients randomly assigned to active treatment at baseline.

At week 52, in both studies 79.1% to 84.9% of the 15 mg and 84.4% to 84.9% of the 30 mg cohort participants achieved 75% reduction from baseline in Eczema Area and Severity Index (EASI-75), 52.6% to 59.2% and 62.5% to 65.1% achieved Validated Investigator Global Assessment for AD clear or almost clear (vIGA-AD 0/1), and 62.4% to 67.3% and 67.7% to 72.9% achieved Worst Pruritus Numerical Rating Scale (WP-NRS) improvement of 4 or greater, respectively.

In general, patients who reported improvements to the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), and Atopic Dermatitis Impact Scale (ADerm-IS) as early as week 16 maintained their improved status through week 52.

A total of 3.0% to 5.6% of 15 mg and 3.4% to 4.9% of 30 mg upadacitinib recipients who responded at 16 weeks lost their response by week 52.

In the 15 mg and 30 mg upadacitinib cohorts, the rates of any treatment-emergent adverse events were 252.0 and 301.7 per 100 person-years (py) and serious adverse events were 6.8 and 8.5 per 100 py, respectively. Adverse events occurred at a lower rate during the Measure Up 2 trial. A total of 43 and 70 of the 15 mg and 30 mg cohort participants discontinued treatment due to adverse events, respectively.

This study was limited by the lack of diversity among the study population.

The study authors concluded that upadacitinib was found to be safe and effective through week 52 for the treatment of AD among adolescents and adults. They indicated that a longer-term follow-up through week 260 is planned.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Simpson EL, Papp KA, Blauvelt A, et al. Efficacy and safety of upadacitinib in patients with moderate to severe atopic dermatitis analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials. JAMA Dermatol. 2022;e220029. doi:10.1001/jamadermatol.2022.0029