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 DERMATOLOGY 39 37-38 2012年6月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 S5-S5 2012年5月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 132 S10-S10 2012年5月
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皮膚科の臨床 54(5) 725-728 2012年5月1日35歳女性。全身性の汎発性膿疱性乾癬に対するインフリキシマブ投与中に局面型の乾癬皮疹が出現した。インフリキシマブを中止し、アダリムマブ(80mg/2週)を開始したところ、12週後にはPASIスコア0を達成し、以後、寛解を維持している。
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Skin Cancer 27(2) 179-185 2012年過去20年間に,当科で経験した乳房外Paget病82例について統計的に検討した。平均年齢71.4歳,男女比が1.8対1。初診時,病変が外陰部に存在していたのは70例(89.7%),腋窩に存在していたのは6例(7.7%),下腹部,肛囲ではそれぞれ2例(2.6%)であった。そのうち,3例がいわゆる多発例であった。リンパ節転移は8.5%にみられ,全てT2以上の症例であった。局所再発は4.1%で全てT1症例であった。5年生存率は,所属リンパ節転移のない群で100%,片側リンパ節転移群で65%,両側リンパ節転移群で0%であった。病期別5年生存率は,病期Ⅰ,Ⅱは100%,病期Ⅲでは75%,病期Ⅳでは0%であった。生存曲線は,病期分類別とN分類別とで類似しており,所属リンパ節転移の有無が予後に大きく影響していることが示された。
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医学のあゆみ 238(6) 707-711 2011年8月6日
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 131 S46-S46 2011年4月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 131 S2-S2 2011年4月
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日本皮膚科学会雑誌 121(8) 1561-1572 2011年Clinical use of TNFα (tumor necrosis factor α) inhibitors, adalimumab and infliximab, for psoriasis began in January 2010 when an additional indication for this disease was approved. In January 2011, an interleukin-12/23 p40 (IL-12/23 p40) inhibitor, ustekinumab, was newly approved as the third biologic agent with an indication for psoriasis. All of these biologic agents are expected to exhibit excellent efficacy against not only psoriasis but also psoriatic arthritis, and to contribute to the improvement of quality of life (QOL) of psoriatic patients. At the same time, however, they require safety measures to prevent adverse drug reactions such as serious infections. We therefore decided to prepare this Guideline/Safety Manual for the Use of Biologic Agents in Psoriasis (The 2011 Version) by revising that for the use of TNFα Inhibitors prepared by the Biologics Review Committee of the Japanese Dermatological Association in February 2010. In this new unified version for all three biologic agents including ustekinumab, requirements for clinical facilities for the use of biologic agents, contents of safety measures against reactivation of tuberculosis and hepatitis B, and recommendable combination therapies with biologic agents, have been renewed and added. This guideline/safety manual has been prepared to assist dermatology specialists experienced in clinical practice of psoriasis to use biologic agents safely and properly.
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稀少難治性皮膚疾患に関する調査研究 平成22年度 総括・分担研究報告書 33-37 2011年
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 130 S85-S85 2010年9月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 130 S52-S52 2010年9月
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 130 S73-S73 2010年4月
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自治医科大学紀要 32 43-49 2010年3月1日1998年から2008年まで, 自治医科大学附属病院皮膚科で経験した121例の悪性黒色腫について統計的に検討した。男性54例,女性67例で,それぞれ年齢分布のピークは60歳代と70歳代にあった。増加傾向にあるが,特に早期病変の症例の増加が著しかった。病型別では末端黒子型が44.6%,悪性黒子型が10.7%,表在拡大型が20.7%,結節型が19.8%であった。5年生存率はstage0が100.0%,stage1が93.3%,stage2が82.6%,stage3が39.4%で,stage4の5年生存率はまだ計算できず,30ヶ月の時点で14.8%であった。早期症例では予後がよく,一般に向けた簡便なスクリーニング法の啓発が今後の課題である。
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日本皮膚科学会雑誌 120(2) 163-171 2010年2月Anti-TNFα (tumor necrosis factor-α) agents, adalimumab and infliximab, are the first biologics approved for the treatment of psoriasis in Japan. Although these agents are expected to have remarkable effects on psoriasis and/or psoriatic arthritis, and to improve QOL (quality of life) of patients with psoriasis, there is growing concern regarding the potential serious adverse reactions such as infections including tuberculosis as well as bacterial and Pneumocystis pneumonia. The guideline and safety manual have been developed to ensure that anti-TNFα agents are properly used by board-certified dermatologists experienced in practice of psoriasis. Requirements for physicians and medical institutions, eligible patients for treatment with anti-TNFα agents, dosage and administration of each anti-TNFα agents, general considerations for administration, contraindications, safety precautions for high-risk patients for adverse reactions, and recommendable combination therapies with anti-TNFα agents are referred.
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稀少難治性皮膚疾患克服のための生体試料の収集に関する研究 平成21年度 総括・分担研究報告書 23-27 2010年
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西日本皮膚科 = The Nishinihon journal of dermatology 72(4) 397-404 2010年
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日本皮膚科学会雑誌 119(11) 2151-2156 2009年10月20日表皮細胞の角化はすなわち表皮細胞の分化である.表皮は角化することにより,適切なバリアー機能を発揮し,外界の刺激から人体を守っている.表皮細胞の分化にあたり,多数の分子が順序良く精密に制御されながら発現している.これらの分子に遺伝的に異常が生じることにより,それぞれ特徴的な臨床症状を発現する遺伝性皮膚疾患が発症する.表皮の角化に影響を与えるもう一つの因子として炎症がある.炎症により発現する炎症性サイトカインによって,表皮の角化・分化に関与する遺伝子の発現が影響を受け,その結果角化の異常が生じる.表皮に生じた異常により,表皮のバリアー機能の破綻をきたしたり,樹状細胞やリンパ球に影響を与えることにより,全身の免疫機能にも影響することが最近の報告で明らかになっている.
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 129 S14-S14 2009年9月
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日本皮膚科学会雑誌 119(5) 863-871 2009年4月20日著明な角化と表皮の増殖性変化から,当初は表皮に乾癬の病態の中心的な異常があると考えられていたが,シクロスポリンの有効性,またSCIDマウスの系において,患者のCD4陽性T細胞が必要なことから,T細胞の役割,なかでも,Th1細胞が病態の中心的役割を担っていると考えられるようになった.最近ではIL-17を産生するTh17細胞が同定され,現在ではこれが乾癬の病態の中心と考えられている.T細胞のTh17細胞への分化は,IL-23を産生する樹状細胞によって制御されているため,樹状細胞の役割も注目されている.抗TNFα抗体や,抗IL-12/23p40抗体が臨床応用されて乾癬に対する有効性が証明されており,これらの理論に臨床的裏づけを与えている.しかしながら乾癬の病変がなぜ皮膚という特異的な臓器に生じるのかについては,いまだ説明がつかない.今後の研究の発展により解明されることを望む.
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JOURNAL OF INVESTIGATIVE DERMATOLOGY 129 S86-S86 2009年4月
共同研究・競争的資金等の研究課題
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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