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

Author

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

Subjects
Atopic dermatitis, dupilumab, Eczema Area and Severity Index, lactate dehydrogenase, Patient-Oriented Eczema Measure, periostin, Immunologic diseases. Allergy, RC581-607
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.

Published
2024
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4. Exploring patient background and biomarkers associated with the development of dupilumab-associated conjunctivitis and blepharitis

Author

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, Ryo Saito, 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, Ayano Fukushima-Nomura, Mamitaro Ohtsuki, Koji Kamiya, Yudai Kabata, Riichiro Abe, Hiroshi Mitsui, Tatsuyoshi Kawamura, Gaku Tsuji, Masutaka Furue, Norito Katoh, and Takeshi Nakahara

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2024
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5. Changes in the structure and physical properties of acrylic and epoxy adhesives in response to high-temperature and high-humidity environments

Author

Yoshiyuki Kamo, Koji Kamiyama, and Akikazu Matsumoto

Subjects
Acrylic adhesive, Epoxy adhesive, Adhesion strength, Moisture absorption, Phase separation, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

The strength of adhesives and adhesive joints degrade due to changes occurring in terms of environmental heat, moisture, and temperature conditions experienced during use. Adhesives with a sea-island phase separated structure consisting of hard and soft domains, are designed to improve reliability when it comes to adhesion. In this study, we investigated the changes occurring in terms of in adhesive strength and phase separated structures during the processes of repeated moisture absorption and desorption for two commercially available adhesives. We measured the adhesive strength of epoxy and acrylic adhesives containing elastomers during dry/wet cycles. The collapse of the phase-separated structures was confirmed via TEM and AFM-IR observations. The changes seen in terms of the continuous structure of the rubbery phase in the acrylic adhesive was greater than that seen in the epoxy adhesive. This caused delamination at the interface located between the adherend and the adhesive. Thus, the adhesive strength of epoxy adhesive has been deemed stable in relation to changes occurring in terms of temperature and humidity.

Published
2024
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6. The ability of biomarkers to assess the severity of atopic dermatitis

Author

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

Subjects
Atopic dermatitis, biomarker, B-PAD, Biomarkers to Predict Clinical Improvement of AD in Patients Treated With Dupilumab, EASI, eotaxin-3, Immunologic diseases. Allergy, RC581-607
Abstract

Background: To develop precision medicine for atopic dermatitis (AD), it is critical to establish relevant biomarkers. However, the characteristics of various biomarkers have not been fully understood. We previously carried out the Biomarkers to Predict Clinical Improvement of AD in Patients Treated with Dupilumab (B-PAD) study, a comprehensive nationwide study in Japan, to explore biomarkers for AD. Objective: The aim of this study is to find biomarkers associated with objective and subjective clinical findings in patients with moderate-to-severe AD based on the B-PAD study and to identify biomarkers sensitive enough to assess the severity of AD. Methods: We performed the B-PAD study as a consortium composed of 19 medical facilities in Japan, enrolling 110 patients with moderate-to-severe AD. We evaluated the Eczema Area and Severity Index (EASI) for objective assessment as well as the Patient-Oriented Eczema Measure (POEM) and a numeric rating scale for pruritus (pruritis-NRS) for subjective assessment, measuring 19 biomarkers at baseline. Results: We found that 12, 6, and 7 biomarkers showed significant and positive associations with the EASI, POEM, and pruritis-NRS, respectively. Most of the biomarkers associated with either the POEM or the pruritis-NRS were included among the biomarkers associated with EASI. Of the biomarkers examined, CCL26/eotaxin-3 and SCCA2 were the most capable of assessing severity for EASI, as shown by the 2 kinds of receiver operating characteristic analyses, respectively, whereas lactate dehydrogenase was the best for both the POEM and pruritis-NRS, again using the 2 analyses. Conclusion: We found biomarkers associated with the EASI, POEM, and pruritis-NRS, respectively, based on the B-PAD study. Moreover, we identified CCL26/eotaxin-3 and/or SCCA2 as the biomarkers having the greatest ability to assess severity in the EASI; lactate dehydrogenase did the same for the POEM and pruritis-NRS. These findings will be useful in treating patients with moderate-to-severe AD.

Published
2024
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