Early and Sustained Improvements in Symptoms and Quality of Life with Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: 52-Week Results from Two Phase III Randomized Clinical Trials (Measure Up 1 and Measure Up 2)

Abstract

Background: Atopic dermatitis is a chronic inflammatory disease characterized by increased itch, skin pain, poor sleep quality, and other symptoms that negatively affect patient quality of life. Upadacitinib, an oral selective Janus kinase (JAK) inhibitor with greater inhibitory potency for JAK1 than JAK2, JAK3, or tyrosine kinase 2, is approved to treat moderate-to-severe atopic dermatitis.

Objective: We aimed to evaluate the effect of upadacitinib on patient-reported outcomes over 52 weeks in adults and adolescents with moderate-to-severe atopic dermatitis.

Methods: Data from two phase III monotherapy trials of upadacitinib (Measure Up 1, NCT03569293; Measure Up 2, NCT03607422) were integrated. Changes in pruritus, pain, other skin symptoms, sleep, quality of life, mental health, and patient impression were evaluated. Patient-reported outcome assessments included the Worst Pruritus Numerical Rating Scale, Patient-Oriented Eczema Measure, Dermatology Life Quality Index, Atopic Dermatitis Symptom Scale, Atopic Dermatitis Impact Scale, Hospital Anxiety and Depression Scale, SCORing Atopic Dermatitis index, Patient Global Impression of Severity, Patient Global Impression of Change, and Patient Global Impression of Treatment. Minimal clinically important differences, achievement of scores representing minimal disease burden, and the change from baseline were evaluated in patients who received upadacitinib through week 52 and in patients who received placebo through week 16.

Results: This analysis included 1609 patients (upadacitinib 15 mg, N = 557; upadacitinib 30 mg, N = 567; placebo, N = 485). Baseline demographics and disease characteristics were generally similar across all arms. The proportion of patients treated with upadacitinib reporting improvements in itch increased rapidly by week 1, increased steadily through week 8, and was sustained through week 52. Patients receiving upadacitinib also experienced improvements in pain and other skin symptoms by week 1, which continued through week 16; improvements were maintained through week 52. Patient reports of improved sleep increased rapidly from baseline to week 1, increased steadily through week 32, and were sustained through week 52. Patients experienced quality-of-life improvements through week 8, which were maintained through week 52. By week 1, patients in both upadacitinib groups experienced rapid improvements in emotional state, and by week 12, patients also achieved meaningful improvements in anxiety and depression. Improvements in mental health continued steadily through week 32 and were maintained through week 52. Patients treated with upadacitinib 30 mg generally experienced improvements in patient-reported outcomes earlier than those treated with upadacitinib 15 mg. Through week 16, patients receiving upadacitinib experienced greater improvements versus those receiving placebo in all assessed patient-reported outcomes.

Conclusions: Adults and adolescents with moderate-to-severe atopic dermatitis treated with once-daily upadacitinib 15 or 30 mg experienced early improvements in itch, pain, other skin symptoms, sleep, quality of life, and mental health that were sustained through week 52.

Clinical trial registration: ClinicalTrials.gov identifiers NCT03569293 (13 August 2018) and NCT03607422 (27 July 2018).

Fig. 1

Improvement in itch (observed case [OC]).^a a Worst Pruritus Numerical Rating Scale (WP-NRS) improvement ≥ 4.^b b WP-NRS 0/1.^c Error bars indicate 95% confidence interval. ^aAssessed daily through week 16, and reported as the weekly average; assessed at scheduled visits thereafter. ^bAssessed in patients with WP-NRS ≥ 4 at baseline. ^cAssessed in patients with WP-NRS > 1 at baseline. PBO placebo, UPA upadacitinib

Fig. 2

Improvement in pain and other skin symptoms (observed case [OC]). a Atopic Dermatitis Symptom Scale (ADerm-SS) Skin Pain improvement ≥ 4.^a b Atopic Dermatitis Symptom Scale 7-item symptom score (ADerm-SS TSS-7) improvement ≥ 28.^b c Patient-Oriented Eczema Measure (POEM) improvement ≥ 4.^c d ADerm-SS Skin Pain 0/1.^d,e e ADerm-SS TSS-7 0–11.^f f POEM 0–2.^g Error bars indicate 95% confidence interval. ^aAssessed in patients with ADerm-SS Skin Pain ≥ 4 at baseline. ^bAssessed in patients with ADerm-SS TSS-7 ≥ 28 at baseline. ^cAssessed in patients with POEM ≥ 4 at baseline. ^dAssessed in patients with ADerm-SS Skin Pain ≥ 2 at baseline. ^eAssessed daily through week 16, and reported as the weekly average; assessed at scheduled visits thereafter. ^fAssessed in patients with ADerm-SS TSS-7 ≥ 12 at baseline. ^gAssessed in patients with POEM ≥ 3 at baseline. PBO placebo, UPA upadacitinib

Fig. 3

Improvement in sleep (observed case [OC]). a Atopic Dermatitis Impact Scale (ADerm-IS) Sleep improvement ≥ 12.^a,b b ADerm-IS Sleep 0–3.^b,c Error bars indicate 95% confidence interval. ^aAssessed in patients with ADerm-IS Sleep ≥ 12 at baseline. ^bAssessed daily through week 16, and reported as the weekly average; assessed at scheduled visits thereafter. ^cAssessed in patients with ADerm-IS Sleep ≥ 4 at baseline. PBO placebo, UPA upadacitinib

Fig. 4

Improvement in daily living, daily activities, and emotional state (observed case [OC]). a Dermatology Life Quality Index (DLQI) improvement ≥ 4.^a b Atopic Dermatitis Impact Scale (ADerm-IS) Daily Activities improvement ≥ 14.^b c ADerm-IS Emotional State improvement ≥ 11.^c d DLQI 0/1.^d e ADerm-IS Daily Activities 0–2.^e f ADerm-IS Emotional State 0–2.^f Error bars indicate 95% confidence interval. ^aAssessed in patients aged ≥ 16 years with DLQI ≥ 4 at baseline. ^bAssessed in patients with ADerm-IS Daily Activities Domain ≥ 14 at baseline. ^cAssessed in patients with ADerm-IS Emotional State ≥ 11 at baseline. ^dAssessed in patients aged ≥ 16 years with DLQI > 1 at baseline. ^eAssessed in patients with ADerm-IS Daily Activities > 3 at baseline. ^fAssessed in patients with ADerm-IS Emotional State > 3 at baseline. PBO placebo, UPA upadacitinib

Fig. 5

Overlap in achievement of Worst Pruritus Numerical Rating Scale (WP-NRS 0/1), Dermatology Life Quality Index (DLQI) 0/1, and Patient-Oriented Eczema Measure (POEM) 0–2 at week 52. Percentages are calculated among patients who received either upadacitinib 15 or 30 mg or achieved ≥ 1 of the following endpoints at week 52: WP-NRS 0/1, DLQI 0/1, or POEM 0–2. The analysis was based on observed cases, including only patients with non-missing data for all three outcome measures at week 52