Biomarkers and patient-related factors associated with clinical outcomes in dupilumab-treated atopic dermatitis

Makiko Kido-Nakahara; Daisuke Onozuka; Kenji Izuhara; Hidehisa Saeki; Satoshi Nunomura; Motoi Takenaka; Mai Matsumoto; Yoko Kataoka; Rai Fujimoto; Sakae Kaneko; Eishin Morita; Akio Tanaka; Michihiro Hide; Tatsuro Okano; Tomomitsu Miyagaki; Natsuko Aoki; Kimiko Nakajima; Susumu Ichiyama; Kyoko Tonomura; Yukinobu Nakagawa; Risa Tamagawa-Mineoka; Koji Masuda; Takuya Takeichi; Masashi Akiyama; Yozo Ishiuji; Michie Katsuta; Yuki Kinoshita; Chiharu Tateishi; Aya Yamamoto; Akimichi Morita; Haruna Matsuda-Hirose; Yutaka Hatano; Hiroshi Kawasaki; Keiji Tanese; Mamitaro Ohtsuki; Koji Kamiya; Yudai Kabata; Riichiro Abe; Hiroshi Mitsui; Tatsuyoshi Kawamura; Gaku Tsuji; Masutaka Furue; Norito Katoh; Takeshi Nakahara

doi:10.1016/j.jacig.2024.100317

Biomarkers and patient-related factors associated with clinical outcomes in dupilumab-treated atopic dermatitis

J Allergy Clin Immunol Glob. 2024 Jul 31;3(4):100317. doi: 10.1016/j.jacig.2024.100317. eCollection 2024 Nov.

Authors

Makiko Kido-Nakahara¹, Daisuke Onozuka², Kenji Izuhara³, Hidehisa Saeki³, Satoshi Nunomura³, Motoi Takenaka⁴, Mai Matsumoto⁴, Yoko Kataoka⁵, Rai Fujimoto⁵, Sakae Kaneko⁶, Eishin Morita⁶, Akio Tanaka⁷, Michihiro Hide⁷, Tatsuro Okano⁸, Tomomitsu Miyagaki⁸, Natsuko Aoki⁹, Kimiko Nakajima⁹, Susumu Ichiyama¹⁰, Kyoko Tonomura¹¹, Yukinobu Nakagawa¹¹, Risa Tamagawa-Mineoka¹², Koji Masuda¹², Takuya Takeichi¹³, Masashi Akiyama¹³, Yozo Ishiuji¹⁴, Michie Katsuta¹⁴, Yuki Kinoshita¹⁵, Chiharu Tateishi¹⁵, Aya Yamamoto¹⁶, Akimichi Morita¹⁶, Haruna Matsuda-Hirose¹⁷, Yutaka Hatano¹⁷, Hiroshi Kawasaki¹⁸, Keiji Tanese¹⁸, Mamitaro Ohtsuki¹⁹, Koji Kamiya¹⁹, Yudai Kabata²⁰, Riichiro Abe²⁰, Hiroshi Mitsui²¹, Tatsuyoshi Kawamura²¹, Gaku Tsuji¹, Masutaka Furue¹, Norito Katoh¹, Takeshi Nakahara¹

Affiliations

¹ Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Oral Microbe Control, Graduate School of Medicine, Osaka University, Osaka, Japan.
³ Division of Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
⁴ Department of Dermatology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
⁵ Department of Dermatology, Osaka Habikino Medical Center, Osaka, Japan.
⁶ Department of Dermatology, Shimane University Faculty of Medicine, Shimane, Japan.
⁷ Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
⁸ Department of Dermatology, St. Marianna University School of Medicine, Kanagawa, Japan.
⁹ Department of Dermatology, Kochi Medical School, Kochi, Japan.
¹⁰ Department of Dermatology, Nippon Medical School, Tokyo, Japan.
¹¹ Department of Dermatology, Course of Integrated Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
¹² Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
¹³ Department of Dermatology, Nagoya University Graduate School of Medicine, Aichi, Japan.
¹⁴ Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan.
¹⁵ Department of Dermatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
¹⁶ Department of Geriatric and Environmental Dermatology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan.
¹⁷ Department of Dermatology, Faculty of Medicine, Oita University, Hasama-machi, Oita, Japan.
¹⁸ Department of Dermatology, School of Medicine, Keio University, Tokyo, Japan.
¹⁹ Department of Dermatology, Jichi Medical University, Tochigi, Japan.
²⁰ Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
²¹ Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.

Abstract

Background: Atopic dermatitis (AD) is a common chronic eczematous skin disease with severe pruritus. Several new therapeutic agents for AD such as dupilumab, an anti-IL-4Rα antibody, have been developed in recent years. We need to predict which agent is the best choice for each patient, but this remains difficult.

Objective: Our aim was to examine clinical background factors and baseline biomarkers that could predict the achievement of improved clinical outcomes in patients with AD treated with dupilumab.

Methods: A multicenter, prospective observational study was conducted on 110 patients with AD. The Eczema Area and Severity Index was used as an objective assessment, and the Patient-Oriented Eczema Measure and Numerical Rating Scale for Pruritus were used as patient-reported outcomes. In addition, some clinical background factors were evaluated.

Results: The achievement of an absolute Eczema Area and Severity Index of 7 or less was negatively associated with current comorbidity of food allergy and baseline serum lactate dehydrogenase (LDH) levels. There were negative associations between achievement of a Patient-Oriented Eczema Measure score of 7 or less and duration of severe AD and between achievement of an itching Numerical Rating Scale for Pruritus score of 1 or less and current comorbidity of allergic conjunctivitis or baseline serum periostin level. Furthermore, signal detection analysis showed that a baseline serum LDH level less than 328 U/L could potentially be used as a cutoff value for predicting the efficacy of dupilumab.

Conclusion: Baseline biomarkers such as LDH and periostin and clinical background factors such as current comorbidity of food allergy and a long period of severe disease may be useful indicators when choosing dupilumab for systemic treatment for AD, as they can predict the efficacy of dupilumab.

Keywords: Atopic dermatitis; Eczema Area and Severity Index; Numerical Rating Scale for Pruritus; Patient-Oriented Eczema Measure; dupilumab; lactate dehydrogenase; periostin.