Baseline Body Surface Area and Itch Severity Define Response to Baricitinib in Patients with Moderate-to-Severe Atopic Dermatitis at Week 16
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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.
| Original language | English |
|---|---|
| Journal | Advances in Therapy |
| Volume | 40 |
| Issue number | 8 |
| Pages (from-to) | 3574-3587 |
| Number of pages | 14 |
| ISSN | 0741-238X |
| DOIs | |
| Publication status | Published - 2023 |
Bibliographical note
Funding Information:
This work was supported by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation, and publication decisions. Support for this assistance was funded by Eli Lilly and Company.
Funding Information:
The authors would like to thank Dr Inmaculada de Torre MD, PhD of Eli Lilly and Company for her scientific input, contribution to the study design and analyses interpretation. We thank the participants of the study. This work was supported by Eli Lilly and Company, which contributed to study design, data collection, data analysis, data interpretation, manuscript preparation, and publication decisions. Support for this assistance was funded by Eli Lilly and Company. Medical writing assistance in the preparation of this article was provided by Joyce O’Grady, PhD, employee of Eli Lilly and Company. Susanne Grond, Christopher Schuster, and Maria Jose Rueda contributed to conception and design of the study. Yun-Fei Chen and Chunyuan Liu performed the statistical analysis. Susanne Grond, Christopher Schuster, Yun-Fei Chen, Chunyuan Liu, Maria Jose Rueda, Jacob P. Thyssen, Marjolein de Bruin-Weller, Antonio Costanzo, Andreas Pinter, and Thomas Bieber contributed to manuscript revision and read and approved the submitted version. Susanne Grond, Chistopher Schuster, Yun-Fei Chen and Maria Jose Rueda are employees and minor shareholders of Eli Lilly and Company. Chunyuan Liu is a consultant from Tigermed-BDM Inc. working for Eli Lilly and Company.
Funding Information:
Susanne Grond, Chistopher Schuster, Yun-Fei Chen and Maria Jose Rueda are employees and minor shareholders of Eli Lilly and Company. Chunyuan Liu is a consultant from Tigermed-BDM Inc. working for Eli Lilly and Company. Jacob P. Thyssen an advisor for AbbVie, Almirall, Arena Pharmaceuticals, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, a speaker for AbbVie, Almirall, Eli Lilly & Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme, and received research grants from Pfizer, Regeneron, and Sanofi-Genzyme. Marjolein de Bruin-Weller has been a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Arena, Aslan, Eli Lilly, Galderma, Janssen, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme. Antonio Costanzo served as advisory board member and consultant, and has received fees and speaker’s honoraria or has participated to clinical trials for Abbvie, Almirall, Biogen, Eli Lilly, LEO Pharma, Janssen, Novartis, Pfizer, Sanofi Genzyme, and UCB-Pharma. Andreas Pinter worked as an investigator and/or speaker and/or advisor for the following pharmaceutical companies: AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Biontec, Böehringer-Ingelheim, Celgene, GSK, Eli Lilly, Galderma, Hexal, Janssen, LEO-Pharma, MC2, Medac, Merck Serono, Mitsubishi, MSD, Norvartis, Pascoe, Pfizer, Tigercat Pharma, Regeneron, Roche, Sandoz Biopharmaceuticals, Sanofi-Genzyme, Schering-Plough and USB Pharma. Thomas Bieber was speaker and/or consultant and/or Investigator for AbbVie, Allmiral, AnaptysBio, Arena, Asana Biosciences, Bayer Health, BioVerSys, Böhringer-Ingelheim, Bristol-Myers Squibb, Celgene, Daichi-Sankyo, Dermavant/Roivant, DermTreat, Domain Therapeutics, DS Pharma, Eli Lilly, Galapagos/MorphoSys, Galderma, Glenmark, GSK, Incyte, IQVIA, Janssen, Kirin, Kymab, LEO Pharma, LG Chem, L´Oréal, MenloTx, Novartis, OMPharma/Vifor, Pfizer, Pierre Fabre, RAPT/FLX Bio, Sanofi/Regeneron, UCB-Pharma. TB is founder of the non-profit biotech company “Davos Biosciences” within the International Kühne-Foundation.
Publisher Copyright:
© 2023, The Authors.
- Atopic dermatitis, Classification and regression tree analysis, Severe itch
Research areas
ID: 368247544