Takizawa, Tsubasa

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Neurology) (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)
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Career 【 Display / hide 】

  • 2010
    -
    2012

    Kawasaki Municipal Hospital

  • 2016

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Instructor

  • 2016
    -
    2018

    Massachusetts General Hospital, Harvard Medical School

  • 2018
    -
    2020

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Instructor

  • 2020
    -
    Present

    Keio University, School of Medicine Department of Internal Medicine (Neurology), Assitant Professor

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Academic Background 【 Display / hide 】

  • 2004
    -
    2010

    Keio University, School of Medicine

  • 2012
    -
    2016

    Keio University, Graduate School of Medicine

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Research Areas 【 Display / hide 】

  • Life Science / General internal medicine

  • Life Science / Neurology

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Research Keywords 【 Display / hide 】

  • Migraine

  • Neurology

  • Cluster Headache

  • Headache

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Papers 【 Display / hide 】

  • Correction: Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis.

    Tokuyasu D, Imai S, Chen SP, Ihara K, Watanabe N, Izawa Y, Nakahara J, Hori S, Takizawa T

    BMC neurology 25 ( 1 ) 40 2025.01

  • Vertebral artery dissection in a patient with migraine treated with calcitonin gene-related peptide monoclonal antibody: a case report and FAERS database analysis

    Daiki Tokuyasu, Shungo Imai, Shin-Pin Chen, Keiko Ihara, Narumi Watanabe, Yoshikane Izawa, Jin Nakahara, Satoko Hori, Tsubasa Takizawa

    BMC Neurology (Springer Science and Business Media LLC)  25 ( 1 ) 1 - 1 2025.01

    　View Summary

    Abstract

    Background

    Migraine is associated with cervical artery dissection (CeAD). Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide with vasodilatory effects. The use of anti-CGRP monoclonal antibodies (CGRP mAb) may affect cerebrovascular disease risk; however, no reports have associated CGRP mAb with CeAD.

    Case presentation and FAERS database analysis

    We report a case of vertebral artery dissection in a 39-year-old woman with migraine treated with galcanezumab. We searched the number of cases where cerebral and cervical artery dissection were reported as adverse effects of CGRP mAb using the FDA Adverse Event Reporting System (FAERS) database. Six and ten such cases were reported regarding galcanezumab and CGRP mAbs use, respectively. The reporting odds ratios for galcanezumab and CGRP mAbs were elevated.

    Conclusion

    Although migraine is reported to be associated with CeAD, the use of CGRP mAb might be related to CeAD and warrant further investigation.

  • Efficacy and Safety of Switching Between Anti-CGRP Monoclonal Antibodies: A Detailed Monthly and Long-term Follow-up Study and Literature Review

    Oshima Kota, Ihara Keiko, Watanabe Narumi, Takemura Ryo, Ishizuchi Kei, Takahashi Nobuyuki, Shibata Mamoru, Nakahara Jin, Takizawa Tsubasa

    Internal Medicine (The Japanese Society of Internal Medicine)  advpub ( 0 )  2025

    ISSN  09182918

    　View Summary

    <p><b>Objective </b>Switching from one anti-calcitonin gene-related peptide monoclonal antibody (CGRP mAb) to another can be beneficial for treating patients with migraine who do not respond well to the first CGRP mAb. However, detailed and long-term follow-up reports of both efficacy and safety remain insufficient. We conducted a case-series analysis of patients with migraine who switched from galcanezumab to erenumab, both belonging to the class of CGRP mAbs. </p><p><b>Methods </b>We conducted a single-center retrospective real-world study. Patients with migraine who first received galcanezumab for ≥3 months and then switched to erenumab at Keio University Hospital were enrolled to investigate changes in monthly migraine days (MMD), response rate, and adverse effects (e.g., injection-site reactions). Additionally, we performed a narrative review of the literature on switching CGRP mAbs. </p><p><b>Results </b>Among the nine patients enrolled, the 50% response rate for MMD was 33% at 3 months after switching. Two patients (22%) initially responded at the 3-month assessment, but later reverted to baseline MMD levels. Switching from galcanezumab to erenumab increased the frequency of constipation, which was typically managed using laxatives. Participants who experienced injection-site reactions tended to exhibit similar reactions regardless of the type of CGRP mAb used. Five patients (56%) demonstrated an improvement in satisfaction after erenumab initiation at least once. A literature review revealed that the characteristics of the cohorts varied among studies. </p><p><b>Conclusions </b>Switching from galcanezumab to erenumab was effective in some patients, while it was associated with some tolerable side effects, and it improved patient satisfaction in approximately half of the patients, despite interindividual diversity in responses and fluctuating responses after switching, which warrants further investigation. </p>

  • Treatment patterns and characteristics of patients with migraine: results from a retrospective database study in Japan.

    Tsubasa Takizawa, Takahiro Kitano, Masahiro Iijima, Kanae Togo, Naohiro Yonemoto

    The journal of headache and pain (Journal of Headache and Pain)  25 ( 1 ) 19 - 19 2024.12

    ISSN  11292369

    　View Summary

    BACKGROUND: Clinical characteristics and treatment practice of patients with migraine in Japan in real-world setting have not been fully investigated. We conducted a retrospective cohort study using claims database to understand the clinical practice of migraine in recent years and to characterize patients potentially not managed well by current treatment options. METHODS: Our study used data from the large claims database maintained by JMDC Inc. Patients with diagnosis of headache or migraine between January 1, 2018, and July 31, 2022, were defined as the headache cohort, and those with migraine diagnosis and prescription of migraine treatments among the headache cohort were included in the migraine cohort. In the headache cohort, characteristics of medical facilities and status of imaging tests to distinguish secondary headache were examined. Treatment patterns and characteristics of patients potentially not managed well by acute/preventive treatment were described in migraine cohort. RESULTS: In the headache cohort, 989,514 patients were included with 57.0% females and mean age of 40.3 years; 77.0% patients visited clinics (with ≤ 19 bed capacities) for their primary diagnosis, and 30.3% patients underwent imaging tests (computed tomography and/or magnetic resonance imaging). In the migraine cohort, 165,339 patients were included with 65.0% females and mean age of 38.8 years. In the migraine cohort, 95.6% received acute treatment while 20.8% received preventive treatment. Acetaminophen/non-steroidal anti-inflammatory drugs were most common (54.8%) as the initial prescription for migraine treatment followed by triptan (51.4%). First treatment prescription included preventive treatment in 15.6%, while the proportion increased to 82.2% in the fourth treatment prescription. Among patients with more than 12 months of follow-up, 3.7% had prescription patterns suggestive of risk of medication-overuse headache, and these patients were characterized by a higher percentage of females and a higher prevalence of comorbidities. CONCLUSIONS: This study revealed that approximately one-fifth of the patients with migraine visiting medical facilities use preventive drugs. The presence of potential patients at risk of medication-overuse headache and the role of clinics in migraine treatment were also described.

  • CGRP-monoclonal antibodies in Japan: insights from an online survey of physician members of the Japanese headache society.

    Tsubasa Takizawa, Keiko Ihara, Narumi Watanabe, Ryo Takemura, Nobuyuki Takahashi, Naoki Miyazaki, Mamoru Shibata, Keisuke Suzuki, Noboru Imai, Norihiro Suzuki, Koichi Hirata, Takao Takeshima, Jin Nakahara

    The journal of headache and pain (Journal of Headache and Pain)  25 ( 1 ) 39 - 39 2024.12

    ISSN  11292369

    　View Summary

    BACKGROUND: Anti-calcitonin gene-related peptide monoclonal antibodies (CGRPmAbs) have greatly changed migraine treatment options. In Japan, although CGRPmAb guidelines (≥ 4 monthly migraine days (MMDs) and ≥ 1 previous preventive failure) are well-acknowledged, the actual use of CGRPmAbs and the circumstances of the related headache care are unknown. METHODS: We conducted an online survey of Japanese Headache Society members, inquiring about the physicians' experience with CGRPmAbs and how they make decisions related to their use. RESULTS: Of the 397 respondents, 320 had prescribed CGRPmAbs. The threshold number of previous preventive failures for recommending a CGRPmAb was two for the majority of the respondents (n = 170, 54.5%), followed by one (n = 64, 20.5%). The MMD threshold was ≥ 4 for 71 respondents (22.8%), ≥ 6 for 68 (21.8%), ≥ 8 for 76 (24.4%), and ≥ 10 for 81 (26.0%). The respondents tended to assess treatment efficacy after 3 months (episodic migraine: n = 217, 69.6%, chronic migraine: n = 188, 60.3%). The cost of CGRPmAbs was described by many respondents in two questions: (i) any request for a CGRPmAb (27.7%), and (ii) the most frequently reported reason for responders to discontinue CGRPmAbs (24.4%). CONCLUSIONS: Most of the respondents recommended CGRPmAbs to patients with ≥ 2 preventive failures, followed by ≥ 1. The MMD threshold ranged mostly from ≥ 4 to ≥ 10. The concern for costs was raised as a major limiting factor for prescribing CGRPmAbs.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • Effects of changes in barometric pressure on mood fluctuations and somatisation: Basic and clinical approaches

    2024.04
    -
    2028.03

    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (A), No Setting

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    我が国で頭痛やめまいの症状を持つ患者数は3,000万人を超えると言われており，それに伴う気分の揺らぎに伴うパフォーマンスの低下は，社会全体の活動低下を招いている．これらの患者のなかには，心的ストレスが原因となって身体の不調を訴える症例が多く含まれているが，なぜそのような身体化の症状が生じるかは十分に解明されていない．本研究では，健常者・身体症状症・片頭痛・メニエール病の患者を対象として，自律神経活動，身体状態の変化を感知する内受容感覚，予測的情報処理に基づく信念形成の特性に着目し，気圧変化に対する身体・認知特性を明らかにする．そして，症状改善に向けたプロトコルの開発に取り組む．

  • Investigation of the Current Epidemiology and Biomarkers of Migraine

    2024.04
    -
    2027.03

    Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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    CGRP関連抗体薬が2021年に上市され、片頭痛診療は大きな変革期を迎えている。そのような中、わが国における頭痛・片頭痛の最新の疫学を明らかにすることは重要と考える。
    片頭痛について、有用なバイオマーカーは確立されていない。
    本研究では、頭痛・片頭痛についての疫学調査を実施する。さらには片頭痛のバイオマーカーの検索などを試みる。

  • Investigation of anti-CGRP monoclonal antibodies and novel therapeutics for migraine

    2022.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Principal investigator

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    片頭痛の病態で重要なカルシトニン遺伝子関連ペプチド（Calcitonin gene-related peptide; CGRP）あるいはその受容体を標的とした抗体治療（CGRP関連抗体薬）が、わが国において2021年に新たに承認となった。
    本研究では、CGRP関連抗体薬を含めた片頭痛の最新治療の実態を明らかにしつつ、今後に向けての新規治療についても検討する。
    慶應義塾大学病院の頭痛外来にてCGRP関連抗体薬のリアルワールドエビデンスを検討した。まず、CGRP関連抗体薬の一つであるガルカネズマブが3回以上投与された片頭痛患者について効果と安全性を検討した。50%反応率（片頭痛日数がベースラインから半分以下になった患者の割合）は62%、100%反応率（片頭痛日数が消失した患者の割合）は10%であった。片頭痛日数のみではなく、随伴症状である光過敏、音過敏、悪心/嘔吐についても65%、50%、64%の患者で改善を認めていた。最も多い有害事象は注射部位反応で、35%の患者で認めていた（Takizawa T et al. BMC Neurology 2022）。
    次に、CGRP関連抗体薬が3回以上投与された片頭痛患者について、どのような臨床的特徴がCGRP関連抗体薬の効果に関連しているのか検討した。治療開始3ヶ月後に、50%反応率を達していた患者をレスポンダー、達していなかった患者をノンレスポンダーと定義した。CGRP関連抗体薬が投与された半数以上の患者がレスポンダーであった。年齢や体重、既往歴、ひと月あたりの片頭痛日数、痛みの程度・性質、予防薬失敗数などのデータを基に解析を行ったところ、①年齢が高く、②予防薬失敗数が少なく、③免疫系疾患の既往がない患者ほどCGRP関連抗体薬のレスポンダーになりやすいことが明らかとなった（Ihara K et al. The Journal of Headache and Pain 2023）。
    その他、わが国におけるCGRP関連抗体薬の学会報告をまとめた総説（大谷星也、井原慶子（co-1st）ら．日本頭痛学会誌 2023）、片頭痛領域の最新治療薬についての総説なども執筆した（Begasse de Dhaem O, Takizawa T (co-1st) et al. Cephalalgia 2023）。
    CGRP関連抗体薬について臨床現場からのリアルワールドデータを基に日本から有効性や安全性、レスポンダーの特徴について初めて英文論文として報告することができた。当初の計画以上に進展していると考えられた。
    CGRP関連抗体薬について、さらに新規を含めた頭痛の治療についても検討を進めていく予定である。

  • 脳血管内皮透過性制御機構の解明による新規神経疾患治療法の確立

    2021.04
    -
    2024.03

    日本学術振興会, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), No Setting

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    脳血管障害は要介護状態となる原因疾患の第一位を占め、2018年に成立した「脳卒中・循環器病対策基本法」の基本理念である、健康寿命延伸の観点から大きな社会的問題となっている。血管内治療など超急性期脳梗塞治療の進歩は目覚ましいが、脳梗塞の発症予防は、いまだ抗血栓療法と血圧管理などに依存し、新規治療法は久しく開発されていない。抗血栓療法は脳出血発症リスクと表裏一体であるなど、脳血管障害の治療で解決すべき課題は多く、脳血管性認知症に至っては治療法が存在しない。安全性と有効性を両立した脳血管障害、さらには脳血管性認知症に対する治療の確立は喫緊の課題である。
    本研究は、内皮に血栓が生じる機序、血管が破綻する機序、神経組織が機能低下する機序の解明を目的とし、脳血管透過性亢進モデルマウスを用いて、血管透過性調節による脳血管障害・血管性認知症の新たな治療概念確立を目指すものである。これにより実臨床で用いられる各抗血栓薬の有効性と安全性の違いや特徴を統一的に説明する理論の確立も目指す。 2021年度は本研究の先行研究結果をまとめた共著論文が提出され、血栓形成（止血）作用を持つトロンビンが脳微小血管障害（血管透過性亢進作用）により脳出血リスクを上昇させる可能性を示したが、これは直感的に想定されるトロンビン作用と真逆の視点を提唱するものである。また、トロンビンが脳微小血管の透過性を上昇させる様子をin vivo、生存下で連続（経時）的に捉えることに成功した。2020年度までの研究成果報告書では統計解析上は、本研究の実験仮説が誤りである可能性も否定できない状況であったが、実験手法改善により、仮説からの予測と一致する結果が蓄積され、統計的評価にも頑健であった。このように、本研究が目標とする「血管透過性制御機構」の解明という観点から、提唱する理論的仮説が真である蓋然性が一定程度高まるデータが得られた。

  • Evaluation of the regulation mechanism of NG2 glia and remyelination under impaired conditions of the central nervous system

    2021.04
    -
    2024.03

    日本学術振興会, Grants-in-Aid for Scientific Research, Unekawa Miyuki, Grant-in-Aid for Scientific Research (C), No Setting

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    We focused on NG2 glia to investigate morphological changes during cerebral ischemia and to investigate the mechanism of improvement of the pathological condition. We established a technique to track longitudinal morphological changes of various cells through a chronic cranial window by Tomita-Seylaz method using the genetically engineered mice expressing fluorescent protein in Sox10, highly coexpressing with NG2, and revealing in oligodendrocytes and their progenitor cells. We tracked morphological changes in various cells by repeated observation using two-photon microscopy for a long duration. Further, we established the middle cerebral artery occlusion technique and found that the occurrence of cortical spreading depolarization is involved in the formation of infarct foci after transient occlusion of cortical branches, and that tissue damage associated with reduced striatal blood flow due to transient occlusion at the origin is involved in the development of neurological deficits.

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Awards 【 Display / hide 】

  • Young Investigator Award, Keio University School of Medicine Alumni Association (Sanshikai)

    2024, Keio University School of Medicine, Sanshikai

  • Frontiers in Headache Research Scholarship

    2018, American Headache Society

  • Kitamura Award

    2014, The Japanese Headache Society

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Courses Taught 【 Display / hide 】

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2025

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2025

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2024

  • LECTURE SERIES, INTERNAL MEDICINE (NEUROLOGY)

    2024

  • RESEARCH FRONTIERS IN BIOMEDICAL SCIENCE

    2023

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