Changes in Methotrexate Polyglutamate Concentrations When Changing From Oral to Subcutaneous Methotrexate Therapy in Methotrexate-naive Patients With Rheumatoid Arthritis: (COSMOS Study)

Methotrexate is known to exist intracellularly as methotrexate polyglutamate, which is formed by the addition of glutamic acid after absorption into the body.
The objective of this study is to measure the concentration of methotrexate polyglutamate in red blood cells and peripheral blood mononuclear cells after initiating methotrexate treatment in patients with rheumatoid arthritis who have no prior history of using methotrexate (either subcutaneous or oral formulations). Additionally, we aim to examine changes in methotrexate polyglutamate concentrations when switching from oral methotrexate to subcutaneous Metoject, as well as to investigate the relationship between methotrexate polyglutamate concentration and the efficacy and safety of the treatment. Another objective of this study is to evaluate whether switching to subcutaneous Metoject allows for an increased maximum tolerable dosage while maintaining safety.

开始日期2025-04-10

申办/合作机构

Keio University

[+2]

JPRN-UMIN000054769

/ SuspendedN/AIIT

Study for building navigation for partial hepatectomy for liver tumors. - Study for building navigation for partial hepatectomy for liver tumors.

开始日期2024-07-15

申办/合作机构

Keio University

JPRN-UMIN000054826

/ SuspendedN/AIIT

Investigation of the association between vitreoretinal diseases and lifestyle-related conditions, including their complications and comorbidities, using big data - Big data and vitreoretinal diseases

开始日期2024-07-01

申办/合作机构

Keio University

100 项与 Keio University 相关的临床结果

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0 项与 Keio University 相关的专利（医药）

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项与 Keio University 相关的文献（医药）

2025-06-01·Journal of autism and developmental disorders

Comparison of the Sensory Profile Among Autistic Individuals and Individuals with Williams Syndrome

Article

作者: Tomiwa, Kiyotaka ; Asada, Kosuke ; Ikeda, Takahiro ; Awaya, Tomonari ; Kimura, Ryo ; Kato, Toshihiro ; Hakuno, Yoko ; Hirai, Masahiro ; Heike, Toshio ; Hagiwara, Masatoshi ; Kato, Takeo ; Ikeda, Ayaka ; Yamagata, Takanori ; Matsushima, Kanae ; Okazaki, Shin

PURPOSE:

With the current study, we aimed to reveal the similarities and differences in sensory profiles between Williams syndrome (WS) and autism spectrum disorder.

METHODS:

Using the sensory profile questionnaire completed by the caregivers, we analyzed the WS (n = 60, 3.4-19.8 years) and autistic (n = 39, 4.2-14.0 years) groups.

RESULTS:

The Severity Analysis revealed a significant group difference in Sensory Sensitivity but not in Low Registration, Sensation Seeking, and Sensation Avoiding subscales. Age can modulate the subscale scores differently across groups. For Sensation Seeking, the scores of both groups decreased with development. However, the scores of Sensory Sensitivity decreased with age in the autistic group but not in the WS group. Sensation Avoiding scores increased with development in the WS group but not in the autistic group. No significant developmental changes were observed in Low Registration.

CONCLUSION:

This study highlights the cross-syndrome similarities and differences in sensory profiles and developmental changes in autistic individuals and individuals with WS.

2025-05-01·Liver International

Differential Pathways Orchestrate Plasma‐Cell Infiltration in Liver Autoimmunity Diseases

Article

作者: Col, E. ; Huard, B. ; Manfroi, B. ; David‐Boudet, L. ; Chemkhi, Z. ; Harada, K. ; Sturm, N. ; Baert, L. ; Mesples, M.

ABSTRACT:

Background & Aims:

Plasma cells (PCs) are frequently infiltrating livers from autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC). However, the molecular pathway(s) implicated remain largely undefined.

Methods:

A retrospective in situ study was performed to assess the cells and molecules involved in PC chemotactism and survival. Relevant in vitro assays were conducted to confirm the activity of the identified molecules.

Results:

We found that myeloid cells producing the PC survival factor a proliferation‐inducing ligand (APRIL) were present in livers from both diseases. Notably, APRIL density both at the level of producing cells and tissue retention of their secreted product correlated with PC accumulation in portal tracts from AIH but not PBC. PCs from AIH livers expressed the B‐cell maturation antigen and CD138 as the APRIL (co)receptors. Consequently, AIH liver PCs responded to APRIL stimulation with an increase in vitro survival. We further identified IL‐16 produced by infiltrating lymphocytes as a chemokine involved in PC recruitment. IL‐16 expression also correlated with PC accumulation in portal spaces from AIH but again not from PBC. Follow‐up biopsies in AIH showed that treatment expectedly reduced PC density and affected in a similar way the density of APRIL‐producing cells. Notably, the density of secreted APRIL was less affected. Finally, the density of IL‐16‐producing cells was not affected.

Conclusions:

Our data show that PC infiltration and persistence is under the guidance of different pathways in AIH and PBC. In AIH, treatment leaves the PC chemotactism pathway unaffected, while partly downregulating the survival pathway.

2025-04-01·Lancet Gastroenterology & Hepatology

[18F]fluorodeoxyglucose and [18F]fluorocholine PET-CT for staging optimisation and treatment modification in hepatocellular carcinoma (PET-HCC01): a prospective multicentre study

Article

作者: Levy, Vincent ; Lebtahi, Rachida ; Regnault, Hélène ; Pop, Gabriel ; Bloch-Queyrat, Coralie ; Menu, Yves ; Goulart, Denis Mariano ; Mulé, Sebastien ; Guiu, Boris ; Coilly, Audrey ; Chalaye, Julia ; Maksud, Philippe ; Nahon, Pierre ; Dohan, Anthony ; Nault, Jean-Charles ; Bouattour, Mohamed ; Soussan, Michael ; Sidali, Sabrina ; Roux, Julie ; Montravers, Françoise ; Dioguardi Burgio, Marco ; Sengel, Christian ; Wartski, Myriam ; Boubaya, Marouane ; Hollande, Clémence ; Itti, Emmanuel ; Allaire, Manon ; Pageaux, Georges-Philippe ; Ganne-Carrié, Nathalie ; Sutter, Olivier ; Ronot, Maxime ; Besson, Florent L ; Lequoy, Marie ; Costentin, Charlotte ; Pol, Stanislas ; Lewin, Maïté ; Wagner, Mathilde ; Amaddeo, Giuliana ; Luciani, Alain

BACKGROUND:

The role of PET-CT with [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) and [¹⁸F]fluorocholine ([¹⁸F]FCH) in staging hepatocellular carcinoma and treatment decisions has, to our knowledge, never been prospectively assessed.

METHODS:

We conducted a multicentre prospective study (PET-HCC01) in nine hospitals in France, including patients aged 18 years or older with a first diagnosis of hepatocellular carcinoma classified as Barcelona Clinic Liver Cancer (BCLC) classification A to C (without metastasis). At study inclusion, patients underwent contrast-enhanced liver MRI and liver, chest, and pelvis CT scans. Patients subsequently underwent [¹⁸F]FCH and [¹⁸F]FDG PET-CT. A first tumour staging and treatment decision was recorded by the multidisciplinary tumour board at each centre using morphological imaging, blind to the results of the PET-CTs. After the results of the PET-CTs were revealed, a second tumour staging and treatment decision was recorded. The primary endpoint was the proportion of patients whose treatment was modified by PET-CTs. Analyses were done in the intention-to-image population, consisting of all patients who had undergone at least one PET-CT and were discussed by the multidisciplinary tumour board. This study was registered with ClinicalTrials.gov, NCT04391348.

FINDINGS:

Between July 20, 2020, and April 27, 2023, 230 patients were enrolled. Among the 215 patients included in the intention-to-image population, the median age was 66·0 years (IQR 60·0-71·5), 193 (90%) were male, and 155 (73%) had cirrhosis. Hepatocellular carcinoma was classified as BCLC stage A in 140 (65%) patients, B in 48 (22%), and C without metastasis in 27 (13%) on the basis of morphological imaging. Potential new lesions were identified in 19 (9%) patients by PET-CT (eight by both tracers, six by [¹⁸F]FCH only, and five by [¹⁸F]FDG only) and in six of these patients, follow-up confirmed the diagnosis of hepatocellular carcinoma (one lesion in the adrenal gland, two in bones, two in the lymph node, and one intrahepatic). PET-CT modified BCLC stage in ten patients: disease stage for two patients moved from BCLC A to B, from BCLC A to C for two patients, from BCLC B to C for two patients, and from BCLC C without metastasis to BCLC C with metastasis for four patients. Planned treatment was modified for four patients (2% [95% CI 1-5]), below the prespecified threshold of clinical significance (10%).

INTERPRETATION:

[¹⁸F]FDG and [¹⁸F]FCH-PET-CTs should not be systematically performed for staging a first diagnosis of hepatocellular carcinoma, as they modified treatment decisions only in a minority of patients.

FUNDING:

Programme Hospitalier de Recherche Clinique Inter-regional-PHRC-I2018 (Ministère de la Santé).

项与 Keio University 相关的新闻（医药）

2025-05-26

·鼎康生物

2025日本-中国生物创新生态系统论坛圆满举行

5月22日，由鼎康生物、多宁生物和利穗科技联合主办的2025日本-中国生物创新生态系统论坛(Japan-China Bio-Innovation Ecosystem Forum)在日本东京成功举办。此次论坛聚焦中日生物医药产业在创新、合作、资本与工艺等多个维度的融合与协同，吸引了众多业内专家、学者及企业代表出席，共同探讨中日生物医药生态系统的未来图景。鼎康生物(Chime Biologics)总裁魏建中(Jimmy Wei)发表开幕致辞，并详细阐述了构建日中生物生态系统的全新策略，通过充分利用日本、中国和美国三国在生物制药领域的互补优势，来推动亚太地区生物制药行业的快速发展和进步。通过这种创新合作模式，三国将各自发挥其在基础研究、制造能力和市场验证方面的独特优势，从而加速新药的研发、生产和市场推广过程。鼎康生物 (Chime Biologics) 总裁魏建中 (Jimmy Wei)瑞伏医疗创投基金(Panacea Venture)创始人黄瑞瑨(James Huang)分享了从全球视角出发对亚洲生物医药投资格局的深刻洞察，强调了中国在新药开发、技术转化及资本效率方面的突出优势。他以Panacea的孵化模式与代表性项目HiRO为例，展示了如何推动生物医药企业在亚洲实现从“0到1”的高质量发展。瑞伏医疗创投基金(Panacea Venture) 创始人黄瑞瑨 (James Huang)东京理科大学准教授及庆应义塾大学特任讲师早野元词(Motoshi Hayano)回顾了他在美国创立基因编辑公司并成功商业化的经历，指出基因编辑技术正为精准医疗和新一代药物开发打开新路径，也为中日两国在基因治疗等前沿领域的合作提供了广阔空间。东京理科大学准教授及庆应义塾大学特任讲师早野元词 (Motoshi Hayano)日本企业Chiome Bioscience CEO小池正道(Masamichi Koike)介绍了公司在抗体药物发现及IDD平台建设方面的最新进展。其展示的ADLib®系列技术平台，在靶点筛选和抗体优化方面的独特优势，为复杂疾病靶点提供了解决方案。Chiome Bioscience CEO小池正道 (Masamichi Koike)日本企业Perseus Proteomics CEO 横川拓哉(Takuya Yokokawa)分享了公司在抗体药物开发方面的核心产品管线，尤其是TfR1靶点创新抗癌药物PPMX-T003。公司还展示了独特的抗体筛选技术，这些技术平台旨在针对高难度靶点的药物发现。Perseus Proteomics CEO横川拓哉 (Takuya Yokokawa)在圆桌讨论环节，第一场讨论的主题聚焦于“中日生命科学合作现状与未来趋势”。本场讨论由鼎康生物(Chime Biologics)总裁魏建中(Jimmy Wei)主持，参与讨论的嘉宾包括科望医药(Elpiscience Biopharma)共同创始人、董事长兼首席执行官纪晓辉(Darren Ji)，瑞伏医疗创投基金(Panacea Venture)创始人黄瑞瑨(James Huang)，日本企业Chiome Bioscience CEO小池正道(Masamichi Koike)，CSL Behring研究开发本部总监和田康史(Yasufumi Wada)，以及日本企业Biosys Technologies社长板东泰彦(Yasuhiko Bando)。行业领袖们分享了在推动日中生命科学合作方面的经验和见解。纪晓辉指出，与美国在付款环节耗费大量时间不同，日本在数据讨论方面投入了较多时间，不过，无论是数据讨论还是关系建立，所花费的时间都是值得的。尽管当前中美关系较为紧张，但仍有众多日本企业积极寻求与中国开展合作，黄瑞瑨认为，数据不会说谎，而中国拥有众多优势管线资源。小池正道提到，日本的生物技术行业，包括股票市场在内，目前并不处于一个很好的发展境地。和田康史则表示，新冠疫情已经改变了业务关注的焦点，基因治疗等领域已然成为转折点，如今正越来越聚焦亚洲市场。板东泰彦认为，日本需要提升其创新技术与能力，才能在全球生命科学领域保持竞争力。圆桌讨论：日中生命科学合作——现状与未来趋势第二场圆桌讨论环节，聚焦于话题“日本的R&D与风险资本投资”。讨论由SIF Impact Capital联合创始人三浦丽理(Reiri Miura)主持，参与讨论的嘉宾包括鼎珮集团(VMS Group)合伙人兼医疗健康投资主管伍兆威(Andrew Ng)，先声药业(Simcere)副总裁Briant Zhang，EP-Bio Partners CEO 黑治宏辅(Kosuke Kuronuma)，以及日本企业PhotoQ3 CEO浜窪隆雄(Takao Hamakubo)。嘉宾们就风险资本在生物医药领域的作用展开讨论。三浦丽理深入剖析了日本的风险投资现状。伍兆威指出，目前存在四种不同的投资模式：许可协议，尤其是二期临床试验之后的对外许可；NewCo模式，如今在风险投资领域愈发活跃；政府背景的资助；以及与CRO、CDMO合作以降低IND成本。Briant Zhang提到，受中美关系影响，对中国的投资虽已停滞，但全球投资热度依旧高涨。他还强调中国企业协作对提升开发效率至关重要。黑治宏辅认为，中国企业潜力巨大，中国市场规模庞大。浜窪隆雄则表示，中国市场极具魅力，CDMO技术实力强劲，展现出卓越能力。圆桌讨论：日本风险资本投资——洞察与机遇在全球不确定性的背景下，东亚地区如何构建一个强大的生物工艺生态系统成为了2025年日本-中国生物创新生态系统论坛上的一个重要议题。第三场圆桌讨论环节，聚焦于话题“在全球不确定性中构建强大的生物工艺生态系统”。本场讨论由多宁生物日本BD总监丹野悠司(Yuji Tanno)主持，参与讨论的嘉宾为多宁生物高级副总裁谢华(Leo Xie)，富士胶片和光纯药社长平井嘉信(Yoshinobu Hirai)，利穗科技(Lisure)副总经理罗亮，以及Central Link董事小田直幸(Naoyuki Oda)。嘉宾们围绕供应链安全与合作等话题展开交流。谢华强调疫情及国际政治不稳定对供应链的威胁，与合作伙伴一起提供本土化服务和技术，以推动中日生物制药技术交流与合作。罗亮表示为日本客户提供额外选择，构建稳健的生物供应链。小田直幸认同供应链安全和本地化的重要性，提到多产地、多地区供应链的必要性。平井嘉信作为采购负责人，则肯定优秀的中国合作伙伴努力为客户提供丰富选择和服务，提升抗击风险能力。圆桌讨论：东亚生物工艺协同——构建稳健生态

基因疗法

2025-05-20

·药时空

已在中美欧提交上市！勃林格殷格翰PDE4抑制剂在IPF和PPF两项3期临床达主要终点

近日，全球知名制药企业勃林格殷格翰（Boehringer Ingelheim）宣布，其PDE4抑制剂nerandomilast在治疗特发性肺纤维化（IPF）和进展性肺纤维化（PPF）的两项三期临床试验（FIBRONEER™-IPF和FIBRONEER™-ILD）中均达到了主要终点。然而，尽管试验结果显示出一定的积极意义，但部分华尔街分析师对该药物的“温和”疗效表示失望。在FIBRONEER™-IPF试验中，nerandomilast的两种剂量（9 mg和18 mg）均显著减缓了特发性肺纤维化患者的肺功能下降，与安慰剂相比，患者的用力肺活量（FVC）下降幅度更小。具体而言，在接受nerandomilast治疗的患者中，FVC的平均下降量为114.7 ml，而安慰剂组为183.5 ml。此外，该药物在与现有抗纤维化药物（如Ofev和Esbriet）联合使用时也显示出一定的疗效。复合关键次要终点（首次急性IPF加重的时间、首次因呼吸原因住院或死亡）未达到。在FIBRONEER™-ILD试验中，nerandomilast同样达到了主要终点，在接受nerandomilast治疗的患者中，FVC的平均下降量为98.6 ml，而安慰剂组为165.8 ml。表明其在减缓进展性肺纤维化患者肺功能下降方面具有潜力。Nerandomilast在复合关键次要终点（到首次急性加重的时间，因呼吸系统原因住院或死亡）方面没有统计学意义，但两个治疗组的死亡率都较低：9 mg组（n=33/8.4%）， 18 mg组（n=24/6.1%），与安慰剂组（n=50/12.8%）相比。两项试验的安全性数据与安慰剂组相当，未出现与药物相关的严重不良事件。尽管试验结果积极，但部分分析师对nerandomilast的疗效持谨慎态度。Leerink Partners的分析师在5月19日的一份报告中指出，nerandomilast虽然在一定程度上优于Ofev，但本质上仍是一种“减缓疾病进展”的药物，而非“阻止疾病进展”的药物。他们认为，该药物对肺功能的影响“温和”，不太可能立即改变IPF的治疗格局。此外，nerandomilast与现有药物的联合使用存在一定的复杂性。例如，与Esbriet存在药物相互作用，低剂量的nerandomilast在与Esbriet联合使用时未能改善患者预后。同时，高剂量nerandomilast的腹泻发生率较高（41%），尤其是在与Ofev联合使用时。这些因素可能会限制其在临床中的广泛应用。尽管面临分析师的质疑，勃林格殷格翰对nerandomilast的前景仍持乐观态度。公司表示，nerandomilast的试验结果为IPF和PPF患者带来了新的希望。nerandomilast治疗特发性肺纤维化（IPF）和进行性肺纤维化（PPF）的新药申请已在美国、中国和欧盟提交，其他地区也将跟进中。结束语：勃林格殷格翰的nerandomilast在纤维化肺病的三期试验中取得了积极进展，尽管被华尔街认为疗效“温和”，该药物的成功仍为IPF和PPF患者带来了新的治疗选择，也为未来的肺纤维化研究提供了新的方向。未来，随着更多数据的公布和临床应用的推进，nerandomilast的潜力有望得到更全面的评估。识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

临床3期临床结果临床成功申请上市优先审批

2025-05-08

·otsuka.co.jp

Otsuka Signs Joint Research Agreement with Keio UniversityIndustry-academia collaboration for infrastructure development toward the social implementation of psychedelics in Japan

RSS Otsuka Pharmaceutical Co., Ltd. (Otsuka) today announces that it has signed a basic research (non-clinical research) agreement with Keio University (Keio) for infrastructure development toward the social implementation of psychedelics in Japan. Conventional treatments for depression, anxiety, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD)--such as antidepressants, augmentation therapy, and cognitive behavioral therapy--are often insufficient in terms of treatment efficacy and relapse prevention. As a result, many patients and their families suffer from the illness and associated decline in social functioning. Economic and social losses are also significant, and there is a strong demand for the development of new treatments for refractory mental disorders. Furthermore, clinical trial results conducted outside Japan on psychedelics such as psilocybin have indicated long-lasting antidepressant effects (6 to 12 months) with just one or two doses. Psilocybin acts as a 5-HT2A receptor agonist and has been confirmed to have a strong and fast-acting antidepressant effect.*1,2 Treatments using psychedelics have been designated as breakthrough therapies in the United States, with multiple pharmaceutical companies conducting phase 3 trials. Phase 2 trials are also underway in Europe. In contrast, in Japan, no clinical trials for psychedelic candidates have been conducted. Only small-scale specific clinical research, led by Professor Hiroyuki Uchida of the Department of Psychiatry and Neuroscience at Keio University School of Medicine, is being carried out with a research grant from the Japan Agency for Medical Research and Development (AMED) under the Research and Development Grants for Comprehensive Research for Persons with Disabilities (in the field of mental disorders) program. In order to safely and appropriately deliver psychedelics to patients in Japan, numerous challenges must be addressed for successful social implementation, as listed below. Key issues for social implementation of psychedelics ・ Optimal clinical trials designed to maximize the therapeutic potential of psychedelics ・ Establishment of a system for the professional development of psychiatrists and psychologists and the development of a system for implementing medical institutions ・ Addressing legal and ethical issues and regulatory compliance related to the use of psychedelics ・ Public awareness campaigns to correct social prejudices and misconceptions about psychedelics Otsuka and Keio have outlined several development items in their joint basic research to deliver psychedelics developed overseas to patients in Japan in the future. These items include consideration of development policies for psychedelics, formulating treatment manuals and guidelines, developing expert training programs, addressing legal and ethical issues, conducting public relations and public awareness campaigns, and promoting corporate collaboration and intellectual property strategies. Otsuka and Keio are committed to addressing these challenges to establish a new standard for treating mental disorders in Japan through the clinical application of psychedelics. *1 Gukasyan N et al. J Psychopharmacol. 2022;36:151-158 *2 Carhart-Harris RL et al. Lancet Psychiatry. 2016;3:619-627; Goodwin G, et al. N Engl J Med. 2022;387:1637-1648

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药物(靶点)	适应症	全球最高研发状态

VEGFR-1/2 peptide vaccine(Keio University) ( VEGFR1 x VEGFR2 )	胶质瘤更多	临床2期
Oremepermin alfa ( Protein kinases )	肌萎缩侧索硬化更多	临床2期
iPS cell-derived neural precursor/stem cells(Keio University)	脊髓损伤更多	临床阶段不明
Target PAI-1 peptide vaccine(Keio University) ( PAI-1 )	冠状病毒感染更多	临床前
RK -pulsed autologous APCs(Ambicion KK)	肿瘤更多	临床前