基本情報
- 所属
- 自治医科大学 医学部 皮膚科学講座 /医師・研究者キャリア支援センター 教授東京大学医学部 非常勤講師
- 学位
- 医学博士(東京大学)
- J-GLOBAL ID
- 201401086537031824
- researchmap会員ID
- B000238728
- 外部リンク
研究キーワード
30経歴
2-
2018年8月 - 現在
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2007年6月 - 2018年7月
論文
231-
The Journal of dermatology 2023年11月30日Plaque psoriasis (PsO) is a chronic immune-mediated inflammatory disease with skin lesions accompanied by an inflammation-related comorbidity risk. The development of various oral drugs and biologics for PsO has provided increasing systemic treatment options for patients with PsO, and the guidance regarding the use of biologics and PsO treatment schemes are widespread in Japan. However, no comprehensive guidelines regarding systemic drug use are available, and the current treatment patterns of systemic drugs for PsO in Japan remain unclear. We conducted a retrospective chart review to clarify the current treatment patterns of systemic drugs for PsO. We enrolled 114 patients who started systemic drugs for PsO between January 2017 and December 2020 at four institutes, with a mean follow-up of 37.2 months. The mean disease duration was 7.8 (standard deviation 9.5) years at the systemic drug initiation. Of all the patients, 78.1% started with oral drugs (phosphodiesterase [PDE] 4 inhibitors 56.1%. calcineurin inhibitors 14.0%. vitamin A derivatives 7.9%), whereas 21.9% started with biologics (interleukin [IL]-17 inhibitors 9.6%. tumor necrosis factor inhibitors 7.0%. IL-23 inhibitors 3.5%. IL-12/23 inhibitors 1.8%). Oral drugs had shorter drug persistence than biologics: the 12-month persistence of the oral drugs vitamin A derivative, calcineurin inhibitor, and PDE4 inhibitor, was 35.5%, 25.8%, and 60.1%, respectively, compared with that of the biologics IL-23 and IL-17 inhibitors, which was 85.6% and 84.7%, respectively. During the study period, the incidence of treatment changes was 59.1/100 patient-years. Lack of efficacy was the most common reason for treatment changes from monotherapy (34.1%). This retrospective medical chart review allowed us to understand the real-world, long-term treatment patterns of systemic drugs for PsO and the relationships between the reasons for treatment changes and subsequent treatment selection, indicating that there is still room for improvement in the appropriate use of systemic drugs for PsO in Japan.
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The Journal of dermatology 50(5) e138-e150 2023年5月This is the English version of Japanese guidance for the use of oral Janus kinase (JAK) inhibitors (JAK1 and tyrosine kinase 2 [TYK2] inhibitors) in the treatments of psoriasis. Several cytokines, such as interleukin (IL)-6, IL-7, IL-12, IL-21, IL-22, IL-23, interferon (IFN)-α, and IFN-γ, are involved in the pathogenesis of psoriasis (including psoriatic arthritis). As oral JAK inhibitors hinder the JAK-signal transducers and activators of transcription signal transduction routes involved in the signal transduction of these cytokines, they may be effective for the treatment of psoriasis. JAK has four types: JAK1, JAK2, JAK3, and TYK2. Regarding the use of oral JAK inhibitors for the treatment of psoriasis in Japan, indications of the JAK1 inhibitor upadacitinib were extended also to psoriatic arthritis in 2021, and the use of the TYK2 inhibitor deucravacitinib for plaque-type psoriasis, pustular psoriasis, and erythrodermic psoriasis became covered by health insurance in 2022. This guidance was developed for board-certified dermatologists who specialize in the treatment of psoriasis and to promote the proper use of oral JAK inhibitors. In the package inserts and guides for appropriate use, upadacitinib and deucravacitinib are classified as a "JAK inhibitor" and a "TYK2 inhibitor", respectively, and it is possible that there may be differences in safety between the two drugs. The safety of these drugs will be evaluated for the future by the postmarketing surveillance for molecularly targeted drugs for psoriasis of the Japanese Dermatological Association.
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The Journal of dermatology 2023年3月20日This real-world study at a single academic center retrospectively examined the drug survival of apremilast for patients with psoriasis. Retrospective information was extracted from the medical records of patients with psoriasis treated with apremilast at the Department of Dermatology, Jichi Medical University Hospital, between March 1, 2017, and June 31, 2021. In total, 281 patients were included in this study. Of these patients, 22% had psoriatic arthritis and 57% had a history of prior systemic treatment, including biologics, before the initiation of apremilast. The 1-, 2-, 3-, and 4-year drug survival rates were 54%, 41%, 32%, and 30%, respectively. Cox regression analysis revealed that sex, duration of plaque psoriasis (<10 years vs ≥10 years), presence of psoriatic arthritis, involvement of scalp lesions, involvement of palmoplantar lesion, involvement of nail lesions, having cardiometabolic comorbidities, and a history of prior systemic treatment did not have any significant impact on drug survival. The most common reason for apremilast discontinuation was inadequate efficacy (27%), followed by adverse events (12%). Approximately 49% of the patients experienced one or more adverse events. Diarrhea was the most common adverse event (24%), followed by nausea (19%) and headache (11%).
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Scientific reports 13(1) 4384-4384 2023年3月16日Narrow band-ultraviolet B (NB-UVB) is an effective treatment for psoriasis. We aim to generate a potential mechanism of NB-UVB through comparing the transcriptomic profile before and after NB-UVB treatment between the peripheral edge of lesional skin (PE skin) and the center of lesional skin (CE skin) on the basis of molecular mechanisms of these two areas display different downstream functions. More than one-fourth of the NB-UVB-altered genes were found to be plaque-specific. Some of them were psoriasis signature genes that were downregulated by NB-UVB in, both, PE and CE skin (core alteration), such as IL36G, DEFB4A/B, S100A15, KRT16, and KRT6A. After NB-UVB treatment, the activity score of upstream cytokines, such as interferons, interleukin (IL)-6, IL-17, and IL-22 in pathogenesis decreased. In addition, NB-UVB could restore normal keratinization by upregulating LORICRIN and KRT2, particularly in the CE skin. Finally, we illustrated that NB-UVB is capable of suppressing molecules from the initiation to maintenance phase of plaque formation, thereby normalizing psoriatic plaques. This finding supports the usefulness of NB-UVB treatment in clinical practice and may help in the development of new treatment approaches in which NB-UVB treatment is included for patients with psoriasis or other inflammatory skin diseases.
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The Journal of dermatology 2023年2月20日Long-term psoriasis (PsO) management remains challenging. With growing variation in treatment efficacy, cost, and modes of administration, patient preferences for different treatment characteristics are not well understood. A discrete choice experiment (DCE), informed by qualitative patient interviews, was conducted to assess patient preferences for different attributes of PsO treatments; 222 adult patients with moderate-to-severe PsO receiving systemic therapy participated in the DCE web survey. Better long-term efficacy and lower cost were preferred (preference weights p < 0.05). Long-term efficacy had the highest relative importance (RI) and mode of administration was as important as the outcome attributes (efficacy and safety). Patients also preferred oral to injectable administration. In subgroup analyses by disease severity, residence, psoriatic arthritis as a comorbidity, and gender, the trends for each subgroup were the same as the overall population although the extent of RI for administration mode varied. Mode of administration was more important for patients with moderate versus severe disease, or rural versus urban residence. This DCE utilized attributes related to both oral and injectable treatment as well as a broad study population of systemic treatment users. Preferences were further stratified by patient characteristics to explore trends in different subgroups. Understanding the RI of treatment attributes and the attribute trade-offs acceptable to patients helps inform moderate-to-severe PsO systemic treatments decisions.
MISC
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 133 S115-S115 2013年5月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 133 S135-S135 2013年5月
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稀少難治性皮膚疾患に関する調査研究 平成24年度 総括・分担研究報告書 197-200 2013年
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稀少難治性皮膚疾患に関する調査研究 平成24年度 総括・分担研究報告書 27-37 2013年
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皮膚病診療 35(1) 71-74 2013年1月1日<症例のポイント>Crohn病に対しインフリキシマブ投与中に、顔面に皮膚サルコイドを生じた1例を経験した。インフリキシマブをアダリムマブに変更後、皮膚サルコイドは軽快した。一方、原疾患のCrohn病はコントロール不良であった。Crohn病とサルコイドーシスは同一スペクトラム上の疾患である可能性が指摘され、ともに抗TNF-α製剤が有効とされる。一方でCrohn病を含む炎症性疾患に対し、抗TNF-α製剤を使用中にサルコイドーシスを生じた報告が複数なされており、抗TNF-α製剤の逆説的反応の一種と考えられている。(著者抄録)
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Skin Cancer 27(3) 355-360 2013年87歳,男性。1ヵ月前に気付いた腹部の結節が増大してきたため,2009年11月に初診した。心窩部に母指頭大の皮下腫瘤を触知し,単純CTでは腹部脂肪織内に22mm大の筋肉と等吸収を示す腫瘤をみとめた。2ヵ月後に行ったMRIで34mm大に増大し,筋層への浸潤も疑われ,診断目的に生検を行った。病理組織はspindle cell sarcomaの像を呈し,免疫染色ではCD34,SMA,S100蛋白,AE1/AE3は陰性であった。滑膜肉腫を疑い,18番染色体のSS18遺伝子を標的とするbreak-apart probeを用いたFISH解析を行ったところ,分離像が確認され,滑膜肉腫と診断した。2010年3月全身麻酔下に局所切除を行った。局所再発はみられなかったが,術後1年9ヵ月に腰椎,腸骨への多発骨転移が出現した。
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IL-17A up regulates IL-33 expression in keratinocytes; negative feedback loop in psoriatic epidermisJOURNAL OF INVESTIGATIVE DERMATOLOGY 132 S20-S20 2012年9月
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医薬の門 52(4) 304-306 2012年9月表皮角化細胞におけるIL-33産生機構を解明する目的で、表皮におけるIL-33の役割について検討した。培養表皮角化細胞をケラチノサイト(SFM)にEGFとウシ脳下垂体抽出物(BPE)を加えた培地を用いて培養、細胞を刺激する24時間前にEGFとBPEを除いた培地に変更した。阻害剤は刺激の30分前に培地に添加、刺激にはIFN-γ(100U/ml)とTNF-α(30ng/ml)を用いた。その結果、IL-33はIFN-γ刺激で表皮細胞の産生が亢進し、TNF-αが同時に存在することでcalpainによってproformがmature formに変換することが明らかとなった。また、IFN-γ刺激によるIL-33誘導機構はEGF受容体、ERK,p38、JAKを介していることが示唆された。更にmature IL-33が細胞外から働くことによりIL-8産生が誘導され、一方で核内におそらくprofomとして存在する場合にはTNF-α刺激によるIL-8産生を抑制することが明らかとなった。
共同研究・競争的資金等の研究課題
12-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2020年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2019年4月 - 2023年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2016年4月 - 2019年3月
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文部科学省 科学研究費補助金(基盤研究(C)) 2011年 - 2013年