Clinical Tailoring of Baricitinib 2 mg in Atopic Dermatitis: Baseline Body Surface Area and Rapid Onset of Action Identifies Response at Week 16

Abstract

Introduction: Baricitinib, an oral Janus kinase (JAK)1/JAK2 inhibitor, is indicated in the European Union and Japan for treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. In the ongoing, placebo-controlled, phase 3 trial BREEZE-AD5, once-daily oral baricitinib 2-mg monotherapy improved disease in moderate-to-severe AD patients who had an inadequate response or intolerance to topical corticosteroids. This post-hoc analysis aimed to identify responders to baricitinib 2 mg, using a proposed clinical tailoring approach based on baseline body surface area (BSA) affected and early clinical improvement, in BREEZE-AD5.

Methods: Classification and regression tree method was used to evaluate baseline predictors for the proportion of patients achieving ≥ 75% improvement in Eczema Area and Severity Index (EASI75) at week 16 among baricitinib 2-mg-treated patients. Two-by-two contingency tables evaluated the association between early response, defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch Numeric Rating Scale from baseline at weeks 4 or 8, and response at week 16 for the proportion of patients achieving EASI75, validated Investigator Global Assessment for AD (vIGA-AD) score of 0 or 1, or ≥ 4-point improvement in Itch (Itch ≥ 4), respectively. Missing data were imputed as non-responder.

Results: At week 16, EASI75 and vIGA-AD (0,1) were achieved by 37.5% and 31.7% of baricitinib 2-mg-treated patients with baseline BSA 10-50% compared with 9.5% and 4.8% with BSA > 50%. Early response in skin inflammation or itch at week 4 was associated with corresponding EASI75, vIGA-AD (0,1), and Itch ≥ 4 of 55.4%, 48.2%, and 39.3% at week 16, while early response at week 8 was associated with 66.7%, 56.1%, and 42.1% of patients achieving these endpoints.

Conclusion: Baseline BSA of 10-50% and early clinical improvement after 4 or 8 weeks of baricitinib 2-mg treatment may identify patients most likely to benefit from long-term baricitinib 2-mg therapy.

Clinical trial registration: NCT03435081.

Keywords: Atopic dermatitis; Baricitinib; Body surface area; Clinical tailoring; Clinical trial; Janus kinase inhibitor.

© 2021. The Author(s).

Figures

Fig. 1

Clinical response by baseline BSA category. Proportion of patients achieving A a 75% improvement in total EASI score, B a vIGA-AD score of 0 or 1, or C a ≥ 4-point improvement in the Itch NRS response over time, among patients who had a baseline BSA of 10–50% or > 50%. aAssessed for patients with a baseline Itch NRS score ≥ 4. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001 for baricitinib 2 mg compared with placebo. BSA body surface area, EASI75 75% improvement in Eczema Area and Severity Index score, NRS Numeric Rating Scale, vIGA-AD (0,1) validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1

Fig. 2

Clinical response over time by early response in skin inflammation or itch at week 4 or week 8 among patients with baseline BSA 10–50%. Proportion of patients achieving (A, B) a 75% improvement in total EASI score, (C, D) a vIGA-AD score of 0 or 1, or (E, F) a ≥ 4-point improvement in the Itch NRS response over time, among patients with a baseline BSA of 10–50% by early response at week 8 (A, C, E) or week 4 (B, D, F). Early response in skin inflammation or itch was defined as ≥ 50% improvement in BSA or ≥ 3-point improvement in Itch NRS, respectively. aAssessed for patients with a baseline Itch NRS score ≥ 4. BSA body surface area, EASI75 75% improvement in Eczema Area and Severity Index score, NRS Numeric Rating Scale, vIGA-AD (0,1) validated Investigator Global Assessment for Atopic Dermatitis score of 0 or 1