Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial

Abstract

Background: Baricitinib is an oral, selective, reversible Janus kinase 1/2 inhibitor approved in the European Union and Japan and under investigation in the United States for treatment of atopic dermatitis (AD).

Objectives: To evaluate the impact of baricitinib plus background topical corticosteroids (TCS) on health-related quality of life (HRQoL), how AD symptoms impact work productivity and life functioning, and treatment benefit using patient-reported outcome (PRO) assessments in patients with moderate-to-severe AD previously experiencing inadequate response to TCS.

Methods: Adult patients with AD in BREEZE-AD7, a Phase 3, multicentre, double-blind trial, were randomised 1 : 1 : 1 to daily oral placebo (control) or baricitinib 4- or 2-mg plus TCS. PROs reported Week 1 through Week 16: Dermatology Life Quality Index (DLQI), Work Productivity and Activity Impairment-AD (WPAI-AD); Patient-Reported Outcomes Measurement Information System (PROMIS) Itch and Sleep measures, and Patient Benefit Index (PBI). Data were analysed using logistic regression (categorical) and mixed model repeated measures (continuous). PBI scores were analysed using analysis of variance.

Results: A total of 329 patients were randomised. Treatment with baricitinib 4-mg (N = 111) or 2 mg (N = 109) plus TCS led to rapid, statistically significant improvements [vs. TCS plus placebo (N = 109)] in DLQI ≥4-point improvement starting at Week 2 (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05), change from baseline in WPAI-AD presenteeism at Week 1 (4-mg plus TCS, P ≤ 0.01; 2-mg plus TCS P ≤ 0.05) and PROMIS itch interference at Week 2 (4-mg plus TCS P ≤ 0.01). Improvements were sustained through Week 16 for baricitinib 4-mg. Statistically significant improvements were observed at Week 16 for PBI global score (4-mg plus TCS, P ≤ 0.001; 2-mg plus TCS P ≤ 0.05).

Conclusions: Baricitinib plus TCS vs. placebo plus TCS showed significant improvements in treatment benefit at Week 16 and rapid significant improvements in HRQoL and impact of AD symptoms on work productivity and functioning through 16 weeks.

© 2021 Eli Lilly and Company. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.

Figures

Figure 1

Dermatology Life Quality Index Outcomes (NRI). Proportion of patients achieving (a) 4 or more point improvement in DLQI total score; (b) a DLQI total score ≤5; and (c) a 0 or 1 on the DLQI, in patients receiving BARI 4‐, 2‐mg and placebo plus TCS through Week 16. P‐values for BARI vs. PBO: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, BARI, baricitinib; BL, baseline; DLQI, Dermatology Life Quality Index; NRI, non‐responder imputation; Nx, number of patients with non‐missing values; PBO, placebo; TCS, topical corticosteroids. Table beneath the graph includes number of patients with non‐missing values at the indicated time points. Patient population includes all randomised patients. Patients from the analysis shown in panel (a) had a baseline DLQI total score ≥4 and panel (b) had a baseline DLQI total score >5. DLQI (0,1) categorical data were previously reported. 20

Figure 2

Work Productivity and Activity Impairment (MMRM). Change from baseline in WPAI‐AD (a) activity, (b) presenteeism, (c) absenteeism and (d) work productivity loss domains for BARI 4‐, 2‐mg and PBO plus TCS at Weeks 1, 2, and 16. P‐values for BARI vs. PBO: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. BARI, baricitinib; MMRM, mixed effect repeated measures; Nx, number of patients with non‐missing values; PBO, placebo; TCS, topical corticosteroids; WPAI‐AD, Work Productivity and Activity Impairment‐Atopic Dermatitis. Numbers beneath the graph include number of patients with non‐missing values at the indicated time points. Patient population includes all randomised patients. Only employed patients answered questions related to absenteeism, presenteeism and work productivity loss; all patients answered the question related to activity outside of work. Higher scores indicate greater impairment and less productivity.

Figure 3

Patient‐Reported Outcome Measurement Information System Item Banks (MMRM). Change from baseline in PROMIS Itch item banks (a) scratching behaviour, (b) interference, (c) mood and sleep, (d) activity and clothing items, and (e) sleep‐related impairment in patients receiving BARI 4‐, 2‐mg and PBO plus TCS through Week 16. P‐values for BARI vs. PBO: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. BARI, baricitinib; BL, baseline; MMRM, mixed effect repeated measure; Nx, number of patients with non‐missing values; PBO, placebo; PROMIS, Patient‐Reported Outcome Measurement Information System; TCS, topical corticosteroids. Table beneath the graph includes number of patients with non‐missing values at the indicated time points. Table beneath the graph includes number of patients with non‐missing values at the indicated time points. A subset of patients for whom translations were available according to language completed the PROMIS instruments. Patient population includes all randomised patients. PROMIS instrument scores are T scores, where a higher score indicates greater impairment.

Figure 4

Patient Benefit Index. (a) Mean global and subscale scores on the PBI in patients receiving BARI 4‐, 2‐mg and PBO plus TCS at Week 16. (b) Mean PBI global score ≥1 in patients receiving BARI 4‐, 2‐mg and PBO plus TCS at Week 16. P‐values for BARI vs. PBO: *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. BARI, baricitinib; Nx, number of patients with non‐missing values; PBI, Patient Benefit Index; PBO, placebo; TCS, topical corticosteroids. Numbers beneath the graph include number of patients with non‐missing values at the indicated time points. A subset of patients for whom translations were available according to language completed the PBI questionnaires. Patient population includes all randomised patients. Higher PBI scores indicate greater benefit, and patients with PBI of 1 or greater are considered as having at least minimum patient‐relevant treatment benefit.