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.

Janus kinase inhibitors for the therapy of atopic dermatitis

“…This resulted in the approved dosage of 4 mg. A 2-mg dosage is recommended especially for age 75 and older, recurrent infections, or renal function impairment. In another phase III study focusing on quality of life and productivity, this also showed rapid and significant improvement as measured by various scores, including the Dermatology Life Quality Index (DLQI) and Patient Benefit Index (PBI) [ 42 ].…”

Baricitinib: A Review in Moderate to Severe Atopic Dermatitis

“…With regard to other patient-reported outcomes, significantly (nominal p ≤ 0.01) more baricitinib 4 mg plus TCS than placebo plus TCS recipients achieved a clinically relevant ≥ 4-point improvement from baseline in the DLQI total score, a DLQI total score of 0 or 1 and a DLQI total score of ≤ 5 at week 16 [ 26 ]. Significant (nominal p ≤ 0.01 vs placebo plus TCS) between-group differences in these endpoints were seen at week 2 and all subsequent timepoints thereafter [ 26 ].…”

“…With regard to other patient-reported outcomes, significantly (nominal p ≤ 0.01) more baricitinib 4 mg plus TCS than placebo plus TCS recipients achieved a clinically relevant ≥ 4-point improvement from baseline in the DLQI total score, a DLQI total score of 0 or 1 and a DLQI total score of ≤ 5 at week 16 [ 26 ]. Significant (nominal p ≤ 0.01 vs placebo plus TCS) between-group differences in these endpoints were seen at week 2 and all subsequent timepoints thereafter [ 26 ]. Baricitinib 4 mg plus TCS also provided a nominally significant improvement from baseline in itch (Table 2 ), and nominally significant changes from baseline in the POEM total score (Table 2 ) and the DLQI total score (nominal p < 0.001) compared with placebo plus TCS at week 16 [ 17 ].…”

“…In a post hoc analysis of data from the first week of therapy in BREEZE-AD7, baricitinib 4 mg plus TCS was associated with statistically significant (nominal p ≤ 0.05 vs placebo) improvements in itch and sleep disturbance as early as day 2, with these improvements maintained through to day 7 [ 25 ]. Significantly (nominal p ≤ 0.05) more baricitinib 2 mg plus TCS than placebo plus TCS recipients achieved DLQI total score of 0 or 1 and DLQI total score of ≤ 5 responses, but not a clinically relevant ≥ 4-point improvement from baseline in the DLQI total score response, at week 16 [ 26 ]. Significant (nominal p ≤ 0.05 vs placebo plus TCS) differences were seen from week 2 for the DLQI total score of ≤ 5 response and from week 4 for the DLQI total score of 0 or 1 response [ 26 ].…”

Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis: Focus on Abrocitinib, Baricitinib, and Upadacitinib

“…Regarding side effects, infections and increased blood CPK were the most common reported ones.A pulmonary thromboembolic event in a patient receiving baricitinib 4 mg was reported in BREEZE-AD7. The impact of the combined therapy in the health-related quality of life and productivity of AD patients, as well as the improvement in patient-reported outcomes were also assessed in BREEZE-AD7[22]. Both dosing regimens (2 mg and 4 mg) of baricitinib plus topical corticosteroids induced a rapidbefore week 2 -and significant improvement in several of the evaluated scores (Dermatology Life Quality Index, Work Productivity and Activity Impairment, Patient-Reported Outcomes Measurement Information System Itch and Sleep) when compared to placebo plus topical corticosteroids in the same timepoints.…”