Baseline Body Surface Area and Itch Severity Define Response to Baricitinib in Patients with Moderate-to-Severe Atopic Dermatitis at Week 16

Abstract

Introduction Atopic dermatitis (AD) is a chronic, inflammatory skin disease characterized by heterogeneous clinical phenotypes and high symptom burden, especially through itch. Baricitinib (BARI), an oral Janus Kinase 1/2 inhibitor, is approved in Europe, Japan, and other countries, for treatment of adults with moderate-to-severe AD who are candidates for systemic therapy. This post hoc analysis of a Phase 3 topical corticosteroid (TCS) combination therapy trial (BREEZE-AD7) aims to characterize patients who might benefit most from BARI. Method Classification and regression tree (CART) analysis was used to identify baseline predictors for patients treated with BARI 4-mg, who achieved ≥ 75% improvement in Eczema Area and Severity Index (EASI75), or EASI75 or Itch Numerical Rating Scale (NRS) ≥ 4-point improvement at week 16 (responders), versus non-responders. Subgroup efficacy analyses were performed based on identified predictor variables, combined with Itch NRS < 7/ ≥ 7. Missing data were imputed as non-responder. Results Baseline body surface area (BSA) was identified by CART as strongest variable predicting response to BARI at week 16, with a cut-off around 40% (BSA ≤ 40%). When combining BSA with itch severity, highest response rates were achieved by BARI patients with BSA ≤ 40%/Itch NRS ≥ 7 at baseline. In this subgroup, 69% and 58% of patients treated with BARI 4-mg achieved EASI75 and Itch NRS ≥ 4-point response at week 16, respectively. While these response rates were 65% and 50% for BARI 4-mg patients with baseline BSA ≤ 40%/Itch NRS < 7, they were 33% and 11% in BSA > 40%/Itch NRS < 7, and 32% and 49% in BSA > 40%/Itch NRS ≥ 7 subgroups, respectively. Conclusion Using a machine learning approach, patients with moderate-to-severe AD and a BSA affecting 10–40% and Itch NRS ≥ 7 were characterized as likely to benefit most from BARI 4-mg TCS combination therapy. This was confirmed by subgroup analyses, which showed that these patients are most likely to show favorable response rates in improving AD signs and symptoms, specifically itch, after 16 weeks of treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-023-02528-8.

Baricitinib Improvement Across Regions in Atopic Dermatitis Patients with Baseline Body Surface Area up to 40% and Severe Itch

“…These detailed insights further support individualized patient management and may ultimately help patients access therapies to which they are most likely to respond. As previously reported [8], the BARI itchdominant patient presents with a profound burden at baseline; the mean EASI total score is 20.5, with over one third of the sample exhibiting severe AD (score > 21) and some reaching as high as 30.5. Additionally, this patient subtype presents with severe itch (mean Itch Fig.…”

Management of Patients Affected by Moderate-to-Severe Atopic Dermatitis with JAK Inhibitors in Real-World Clinical Practice: An Italian Delphi Consensus

“…Moreover, dupilumab showed lower effectiveness in patients with significant head, neck, and hand involvement, as recently described by Chiricozzi et al [ 16 ]. On the other hand, baricitinib appears to be more effective in these areas, as described by Thyssen et al [ 17 ]…”

“…No agreement was obtained in the first round for statement 2, which concerned the preferable use of JAK inhibitors over biologics in patients with severe itch. This statement was rewritten according to the members’ suggestions, shifting the focus to the “itch-dominant” phenotype (patients with itch-NRS ≥ 7 and BSA up to 40%) [ 17 ], obtaining the agreement during the second Delphi round.…”

“…In particular, upadacitinib and abrocitinib have demonstrated high rates of EASI 75 and EASI 90 (reduction of at least 75% and 90% of the Eczema Area and Severity Index compared to baseline), along with rapid decrease of the itch and improvement in the quality of life, across all patient groups (biological-naive versus biological-experienced, different phenotypes) [ 4 , 19 ]. Also, baricitinib has shown significant results in terms of EASI 75 and reductions of itch, particularly in the post hoc analysis of BREEZE-AD7 on the itch-dominant profile, showing the importance of a personalized approach in AD therapies [ 17 , 20 ]…”

Baricitinib treatment rapidly improves the four signs of atopic dermatitis assessed by Eczema Area and Severity Index (EASI) clinical subscores

“…A subset of AD patients of special relevance are known as the ‘itch‐dominant phenotype’, who appear to require greater medical attention 24 . It has recently been demonstrated that these patients, defined as having itch NRS ≥7 and 10%–40% affected BSA, are precisely those who are most likely to benefit from baricitinib 25 …”