Rapid and Durable Skin Pain Relief with Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis

Abstract

Itch, skin pain, and eczematous lesions are features of atopic dermatitis (AD). Skin pain is increasingly recognized as both a common and burdensome symptom of AD, reported by 61% of patients, that can impair daily activities, sleep, and mental health.Upadacitinib (UPA) is an oral selective Janus kinase 1 inhibitor approved for the treatment of AD and multiple other conditions. In this study, we assessed the efficacy of UPA in reducing skin pain in adults and adolescents with moderate-to-severe AD. This analysis evaluated integrated data from patients with moderate-to-severe AD treated with UPA monotherapy in two studies: Measure Up 1 and Measure Up 2. Patients were randomized to receive UPA 15mg (UPA15), UPA 30mg (UPA30), or placebo for 16 weeks in the double-blind, placebo-controlled period. At week 16, patients randomized to UPA groups continued treatment, and placebo groups were re-randomized to UPA15 or UPA30 for the double-blind, long-term extension period. Skin pain (SP) was assessed using a validated patient-reported outcome (PRO) measure, the Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain numerical rating scale (NRS); the optimal outcome was defined as an SP-NRS score of 0 or 1 (SP-NRS 0/1), indicating no/minimal skin pain. Among patients who achieved SP-NRS 0/1 at week 16, long-term maintenance of response was evaluated through week 140. Patient-reported impacts of achieving SP-NRS 0/1 on sleep, daily activities, and quality of life (QOL) outcomes were assessed. Response rates were based on non-responder imputation (NRI) through week 16 and observed cases (OC) through week 140. At baseline, 85% of patients reported skin pain. Compared with placebo (n=531), patients treated with UPA15 (n=524) and UPA30 (n=543) achieved higher rates of SP-NRS 0/1 as early as day 2 (the day after treatment initiation), with response rates increasing through day 28 (UPA15: 43.7%, UPA30: 57.6%; both p<0.001). Both UPA15 and UPA30 groups had greater achievement of SP-NRS 0/1 compared with placebo at week 16 (UPA15: 41.9%; UPA30: 58.0%; placebo: 10.8%; NRI, both p<0.001). Response rates were sustained through week 140 in the overall population (UPA15: 63.8%; UPA30: 72.3%; OC) and among patients who achieved SP-NRS 0/1 at week 16 (UPA15: 78.9%; UPA30: 83.0%). Achieving SP-NRS 0/1 was associated with meaningful improvements across PROs, including sleep quality, daily functioning, and overall QOL. In summary, UPA-treated patients experienced rapid (by day 2) and durable reductions in skin pain, with most patients maintaining the optimal target (SP-NRS 0/1) through week 140. Reduction of skin pain was associated with improvements in PROs across multiple dimensions of patients’ lives, reinforcing skin pain as a meaningful and actionable therapeutic target in AD.