| Abstrakt: |
Introduction/Background Atopic dermatitis (AD) is a chronic, recurrent, immune-mediated inflammatory disease associated with burdensome symptoms including itch, skin pain, sleep disruption, as well as reduced quality of life (QoL).1 It is therefore important to consider signs, symptoms, and QoL impairments when evaluating long-term benefits of AD treatments. Upadacitinib is an oral selective Janus kinase inhibitor approved to treat moderate-to-severe AD.2 Objective To evaluate the effects of upadacitinib monotherapy on skin and patient-reported outcomes (PROs) in patients with moderate-to-severe AD over 140 weeks. Methods Measure Up 1 (NCT03569293) and Measure Up 2 (NCT03607422) were replicate, multicenter, phase 3 studies evaluating once-daily oral upadacitinib monotherapy for adolescents (aged 12–17 years) and adults (aged ≥ 18 years) with moderate-to-severe AD.3,4 At baseline, patients were randomized 1:1:1 to upadacitinib 15 mg, upadacitinib 30 mg, or placebo. In this analysis, data for patients who were randomized to upadacitinib 15 mg or upadacitinib 30 mg at baseline in Measure Up 1 and Measure Up 2 were integrated and reported based on observed cases from week 16 (the end of the double-blind period) through week 140 of the blinded extension period; week 16 data for patients randomized to placebo were also reported. Assessments included itch (Worst Pruritus Numerical Rating Scale [WP-NRS]); Eczema Area and Severity Index (EASI); skin pain (AD Symptom Scale [ADerm-SS] Skin Pain); skin symptoms (ADerm-SS 7-item Total Symptom Score [TSS-7]); skin symptom severity (Patient-Oriented Eczema Measure [POEM]); QoL (Dermatology Life Quality Index [DLQI; patients aged ≥ 16 years], and Children's DLQI [CDLQI; patients aged < 16 years]); and sleep, daily activities, and emotional state (AD Impact Scale [ADerm-IS]). Assessed outcomes included achievement of (1) minimal clinically important differences vs baseline (WP-NRS, ADerm-SS Skin Pain, and POEM improvement ≥ 4; ADerm-SS TSS-7 improvement ≥ 28; ADerm-IS Sleep, Daily Activities, and Emotional State improvements ≥ 12, ≥ 14, and ≥ 11, respectively), (2) no/minimal disease burden or impact (WP-NRS 0/1, ≥ 90% improvement from baseline in EASI [EASI 90], DLQI 0/1,and CDLQI 0/1), and (3) simultaneous achievement of EASI 90 and WP-NRS 0/1, an endpoint that aligns with the recently proposed minimal disease activity concept.5 Results Data for 1213 patients (upadacitinib 15 mg, n = 603; upadacitinib 30 mg, n = 610), including 241 adolescents (19.9%) and 972 adults (80.1%), from Measure Up 1 and Measure Up 2 were analyzed. At week 16, over 50% of patients receiving either dose of upadacitinib reported clinically meaningful improvements in PROs; among patients receiving upadacitinib 15 mg and upadacitinib 30 mg, 36.7% and 53.1% achieved WP-NRS 0/1, while 29.0% and 44.1% achieved DLQI 0/1, and 23.5% and 50.0% achieved CDLQI 0/1, respectively. Response rates at week 16 were sustained or improved further through week 140. At week 140, the proportion of patients treated with upadacitinib 15 mg and upadacitinib 30 mg from baseline who achieved clinically meaningful improvements were 64.8% and 70.9% for itch, 74.6% and 81.5% for skin pain, 67.6% and 75.4% for skin symptoms, 89.0% and 94.2% for skin symptom severity, 76.5% and 84.0% for sleep, 79.2% and 84.0% for daily activities, and 78.6% and 82.7% for emotional state, respectively. At week 140, achievement rates with upadacitinib 15 mg and upadacitinib 30 mg were 45.1% and 51.4% for WP-NRS 0/1, 67.3% and 75.6% for EASI 90, 40.5% and 47.1% for simultaneous EASI 90 and WP-NRS 0/1 achievement, 40.2% and 48.5% for DLQI 0/1, and 35.7% and 65.0% for CDLQI 0/1, respectively. Conclusions Patients with moderate-to-severe AD experienced sustained improvements in skin signs/symptoms through 140 weeks while receiving upadacitinib. Rates of long-term PRO improvements were numerically higher with upadacitinib 30 mg compared with upadacitinib 15 mg. [ABSTRACT FROM AUTHOR] |
