Prospective Observational Study to Evaluate Secukinumab Treatment Effectiveness in Pediatric Patients With Active Juvenile Enthesitis-related or Psoriatic Arthritis (Toddler)

This is a multicenter, non-interventional, cohort study in pediatric patients with active juvenile enthesitis-related or psoriatic arthritis

开始日期2025-04-30

申办/合作机构

Novartis Pharmaceuticals Corp.

PER-031-18 / Completed临床3期

A RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL TO ASSESS THE EFFICACY OF SUBCUTANEOUS SECUKINUMAB AFTER TWELVE WEEKS OF TREATMENT, AND TO ASSESS THE LONG-TERM SAFETY, TOLERABILITY AND EFFICACY IN SUBJECTS FROM 6 TO LESS THAN 18 YEARS OF AGE WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS

开始日期2024-11-01

申办/合作机构-

NCT05309616 / Not yet recruiting临床2期IIT

Effects of IL-17A Inhibition on Idiopathic Subglottic Stenosis

The purpose of this phase 2 study is to examine if inhibiting IL-17A activation using the biologic drug Taltz, in idiopathic subglottic stenosis patients will decrease scar fibroblast proliferation therefore reducing or eliminating the need for invasive or repeat surgeries.

开始日期2024-10-01

申办/合作机构

Yale University

100 项与 IL-17A 相关的临床结果

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100 项与 IL-17A 相关的转化医学

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0 项与 IL-17A 相关的专利（医药）

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11,769

项与 IL-17A 相关的文献（医药）

2025-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Metabolic reprogramming and AMPK activation: Key players in the therapeutic effects of Cooling Blood and Detoxicating Formular on psoriasis

Article

作者: Wang, Yazhuo ; Ma, Huike ; Yang, Danyang ; Zhang, Xiawei ; Ma, Yueyue ; Qu, Baoquan ; Li, Lin ; Zhao, Ning ; Meng, Yujiao ; Zhu, Haoyue ; Zhao, Jingxia ; Di, Tingting ; Chen, Jia ; Wang, Yan ; Li, Ping

ETHNOPHARMACOLOGICAL RELEVANCE:

Cooling Blood and Detoxicating Formular (CBDF) based on the theory of cooling blood and dosing detoxification, is a useful traditional Chinese medicine (TCM) medication for psoriasis with blood-heat syndrome.

AIM OF THE STUDY:

Investigate the active constituents and mechanisms of the CBDF for the treatment of psoriasis.

MATERIALS AND METHODS:

UPLC-Q-Orbitrap-HRMS technique was used to analyse the ingredients of CBDF absorbed into plasma and skin tissue. The therapeutic efficacy of CBDF was evaluated in treating an imiquimod (IMQ)-induced mouse model was assessed. Transcriptome analysis and gene enrichment analysis were used to explore the changes in gene expression and pathways following treatment with the CBDF. Validation was performed using western blotting, quantitative RT-PCR, flow cytometry, gene knockout and molecular docking in vitro and in vivo.

RESULTS:

26 compounds were identified in the plasma of IMQ-induced psoriasis-like mouse with CBDF treatment, and higher levels of cimifugin in the lesion. CBDF improved the pathological changes of psoriasis, with inhibition of TNF-α, IL-23, and IL-17A and upregulation of IL-10. Gene enrichment analysis showed that the therapeutic effect of CBDF was related to AMPK pathway. In psoriasis lesions, the AMPK and fatty acid oxidation were suppressed, and glycolysis was enhanced. The Prkaa2, encoding AMPKα2 was down-regulated in psoriasis patients. CBDF inhibited glycolysis while stimulating fatty acid oxidation by the activating AMPK, thereby exerting an inhibitory effect on inflammation. CBDF inhibited MHCII, CD80, and CD86 on dendritic cells of skin drainage lymph node. In vitro, CBDF inhibited bone marrow-derived DCs secrete IL-23, TNF-α, and lactate, while enhanced fatty acid oxidation and AMPK activity. However, the therapeutic effect was weakened in AMPKα2 deletion. Additionally, psoriasis lesions and dendritic cells activation were significantly aggravated after AMPKα2 knockout. The key ingredients of the CBDF, cimifugin, rutin, astilbin, quercetin, and prim-O-glucosylcimifugin, all exhibit a notable affinity towards AMPKα2 binding.

CONCLUSIONS:

CBDF ameliorates psoriasis symptoms and inhibit dendritic cells maturation by regulating metabolic reprogramming in an AMPK-dependent mechanism.

2024-12-31·Gut microbes

Opioid-induced dysbiosis of maternal gut microbiota during gestation alters offspring gut microbiota and pain sensitivity

Article

作者: Singh, Salma ; Roy, Sabita ; Tao, Junyi ; Chupikova, Irina ; Abu, Yaa F ; Singh, Praveen ; Meng, Jingjing

There has been a rapid increase in neonates born with a history of prenatal opioid exposure. How prenatal opioid exposure affects pain sensitivity in offspring is of interest, as this may perpetuate the opioid epidemic. While few studies have reported hypersensitivity to thermal pain, potential mechanisms have not been described. This study posits that alterations in the gut microbiome may underly hypersensitivity to pain in prenatally methadone-exposed 3-week-old male offspring, which were generated using a mouse model of prenatal methadone exposure. Fecal samples collected from dams and their offspring were subjected to 16s rRNA sequencing. Thermal and mechanical pain were assessed using the tail flick and Von Frey assays. Transcriptomic changes in whole brain samples of opioid or saline-exposed offspring were investigated using RNA-sequencing, and midbrain sections from these animals were subjected to qPCR profiling of genes related to neuropathic and inflammatory pain pathways. Prenatal methadone exposure increased sensitivity to thermal and mechanical pain and elevated serum levels of IL-17a. Taxonomical analysis revealed that prenatal methadone exposure resulted in significant alterations in fecal gut microbiota composition, including depletion of Lactobacillus, Bifidobacterium, and Lachnospiracea sp and increased relative abundance of Akkermansia, Clostridium sensu stricto 1, and Lachnoclostridium. Supplementation of the probiotic VSL#3 in dams rescued hypersensitivity to thermal and mechanical pain in prenatally methadone-exposed offspring. Similarly, cross-fostering prenatally methadone-exposed offspring to control dams also attenuated hypersensitivity to thermal pain in opioid-exposed offspring. Modulation of the maternal and neonatal gut microbiome with probiotics resulted in transcriptional changes in genes related to neuropathic and immune-related signaling in whole brain and midbrain samples of prenatally methadone-exposed offspring. Together, our work provides compelling evidence of the gut-brain-axis in mediating pain sensitivity in prenatally opioid-exposed offspring.

2024-12-31·JOURNAL OF DERMATOLOGICAL TREATMENT

Association of disease duration and PASI response rates at week 12 in patients with moderate-to-severe plaque psoriasis receiving biologics in the real-world psoriasis study of health outcomes (PSoHO)

Article

作者: Schuster, Christopher ; Mert, Can ; Costanzo, Antonio ; Papp, Kim A ; Maul, Julia-Tatjana ; Eyerich, Kilian ; Lampropoulou, Anastasia ; Garrelts, Alyssa ; Pinter, Andreas ; Fotiou, Konstantinos

PURPOSE:

Currently, in the treatment of moderate-to-severe psoriasis (PsO) there is a lack of evidence demonstrating optimal biologic treatment response with respect to disease duration. The aim of this post-hoc analysis, using real world data from the Psoriasis Study of Health Outcomes (PSoHO), is to provide evidence if early intervention with biologics is associated with better treatment outcomes and if there is any difference among drug classes or individual biologics.

MATERIALS AND METHODS:

For this post-hoc analysis patients were categorised into two subgroups according to shorter (≤2 years) or longer (>2 years) disease duration. Analysis was performed on anti-interleukin (IL)-17A cohort vs other biologics cohort, anti-IL-17A vs other drug classes, and pairwise comparisons of ixekizumab vs individual biologics, provided that the statistical models converged. Analysis investigated the association of disease duration with the proportion of patients achieving 100% improvement in Psoriasis Area Severity Index score (PASI 100) at week 12. Adjusted comparative analyses, reported as odds ratio (OR), were performed using Frequentist Model Averaging (FMA) for each cohort or treatments within each subcategory of the subgroups.

RESULTS:

At week 12, anti-IL-17A and other biologics cohorts displayed minimal differences in numerical response rate for PASI 100 with respect to disease duration. The anti-IL-17A cohort showed a higher numerical PASI 100 response rate compared to the other biologic cohort irrespective of disease duration (≤2 years: 36.7% vs 21.8%; >2 years: 35.8% vs 21.9%).

CONCLUSION:

Overall, the results do not clearly indicate that treating patients early is critical in achieving optimal patient outcomes. Furthermore, patients treated with ixekizumab show numerically higher response rates relative to other individual biologics irrespective of disease duration.

787

项与 IL-17A 相关的新闻（医药）

2024-09-21

·GlobeNewswire-Health Care

ACELYRIN, INC. Announces Positive Results from Global Phase 3 Clinical Trial of Izokibep in Hidradenitis Suppurativa to be Highlighted in Late-Breaking Oral Presentation at EADV 2024

Sept. 19, 2024 -- ACELYRIN, INC. (Nasdaq: SLRN), a late-stage clinical biopharma company focused on accelerating the development and delivery of transformative medicines in immunology, today announced that positive results from the company’s global Phase 3 clinical trial of izokibep in moderate-to-severe hidradenitis suppurativa (HS) patients will be shared as a late-breaking oral presentation at the 2024 European Academy of Dermatology and Venereology taking place September 25-28, 2024 in Amsterdam, Netherlands. Presentation details are as follows: Title: Efficacy and Safety of Izokibep, a Novel IL-17A Inhibitor, in Moderate-to-Severe Hidradenitis Suppurativa: Week 12 Results from a Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 3 Study Session Type: Late-breaking Oral Presentation Abstract ID: 7995 Date/Time: Wednesday, September 25, 2024; 4:00 – 4:15PM CEST Presenter: Kim Papp, M.D., Ph.D., President and Director of Research, Probity Medical Research, Inc. “The global Phase 3 clinical trial of izokibep as a treatment for HS demonstrated statistically signiﬁcant and clinically meaningful responses across multiple eﬃcacy endpoints – particularly in higher order responses such as HiSCR90 and HiSCR100 – by 12 weeks,” said Shephard (Shep) Mpofu, M.D., Chief Medical Officer of ACELYRIN. “We believe these data could support a path to regulatory approval in this indication and look forward to having the data presented in this important dermatology forum.” Izokibep is a small protein therapeutic designed to inhibit IL-17A with high potency through tight binding aﬃnity, the potential for robust tissue penetration due to its small molecular size – about one-tenth the size of a monoclonal antibody – and an albumin binding domain that extends half-life. It is currently being evaluated in multiple late-stage trials in moderate-to-severe Hidradenitis Suppurativa (HS), moderate-to-severe psoriatic arthritis (PsA), and noninfectious uveitis. Phase 3 HS and PsA data presented to date have demonstrated levels of clinical response comparable with next generation approaches to IL-17 inhibition. ACELYRIN previously announced that it would discontinue internal development of izokibep in HS and PsA. ACELYRIN, INC. (Nasdaq: SLRN) is focused on providing patients life-changing new treatment options by identifying, acquiring, and accelerating the development and commercialization of transformative medicines. ACELYRIN’s lead program, lonigutamab, is a subcutaneously delivered monoclonal antibody targeting IGF-1R being investigated for the treatment of thyroid eye disease. The content above comes from the network. if any infringement, please contact us to modify.

临床结果

2024-09-19

·生物谷

别熬了！仅熬夜4天，死亡率就高达80%！Cell：清华大学研究团队揭示“睡眠不足免疫崩溃”的机制，深层原因在这儿....

人一生中，约有三分之一的时间在睡眠中度过。睡眠的重要性不言而喻，但随着社会飞速发展以及生活节奏加快，“拼命十三郎”们只能舍弃睡眠时间，转而投入996甚至007的“社畜”工作中。除了繁忙的工作压缩了睡眠时间外，一个更常见的现象是“报复性熬夜”——白天被各种琐事儿缠身，只有当晚上躺在床上的那一刻，时间才开始属于自己，接着就是“无止境”的熬夜。当从手机中“缓过神”的时候，发现自己根本睡不了几个小时又要搬砖了！据《中国睡眠研究报告2023》最新公布的数据，2022年中国人的入睡时间集中在23点至1点，比2021年向后推迟了1小时。此外，一项针对中国职场青年的报告显示，超五成职场青年每天在12点之后才睡觉，甚至有13%的要熬到凌晨2点后。不过，正如大家调侃得那样“晚上不睡，白天崩溃”。崩溃的不仅是精神，还有身体的方方面面！早在2007年，国际癌症研究机构（IARC）就把熬夜（包括昼夜节律打乱的轮班工作）定义为2A类致癌物。除此之外，熬夜还会导致主要心血管不良事件的风险增加92%；增加海马体中抑制神经元活动，破坏记忆巩固；甚至于死亡！去年，来自北京生命科学研究所/清华大学生物医学交叉研究院的团队进一步发现，睡眠不足免疫崩溃并非“耸人听闻”——睡眠不足可能会导致严重的病理生理后果，甚至诱发死亡！在长达4天的熬夜之后，生物体表现出严重的炎症反应，约有80%死亡。具体原因在于，睡眠剥夺会增加大脑中前列腺素D2（PGD2）的水平，而穿过血脑屏障的脑源性PGD2外排的增加，会诱发循环中性粒细胞的聚集和细胞因子风暴综合症，给外周免疫系统带去严重的病理后果。 DOI: 10.1016/j.cell.2023.10.025 “长时间的睡眠剥夺会导致生物体的过早死亡”并非新闻，早已在果蝇、小鼠、大鼠和狗等动物模型中得到证实。同时，先前Cell上刊登过哈佛医学院团队的研究揭示，“熬夜至死”的关键原因不在于大脑，而在于肠道。然而，睡眠与健康之间关联性非常复杂，睡眠调节免疫力的详细机制以及睡眠不足影响健康的具体原因仍没有完全阐明。与此同时，控制实验动物的睡眠模式并非易事，想要完全地剥夺小鼠的睡眠，还需要探索出更为规范的实验范式。于是，研究者首先建立了一种改良版的小鼠睡眠剥夺系统，并将该方法命名为“Curling prevention by water（CPW）”。简单来说，CPW范式是指：将小鼠关在一个装有水的笼子里，水位大概8毫米深，刚刚到达小鼠脚踝的位置。当小鼠表现出“身体蜷缩”的打瞌睡样，就会因为鼻子接触到水而迅速被“淹”醒。为了确认CPW的有效性，研究者对小鼠开展了基于EEG/EMG的睡眠/觉醒分析，结果发现：暴露于CPW范式的小鼠确实处于“熬大夜”的状态——小鼠每天有长达1400分钟保持清醒，占全天时长的96%。与对照组相比，CPW小鼠有95%NREMS（约545分钟/天））和83%REMS（54分钟/天）被剥夺。 CPW的厉害之处在于，该范式能够同时极大地消耗小鼠的快速眼动睡眠（REMS）和非快速眼动睡眠（NREMS），且保持较长时间上（>4天）。同时，在排除了混杂因素影响以及与多种方法进行对比后证实，CPW能够有效地模拟“熬夜”，但不会诱发过度的应激或损害代谢平衡。 CPW范式的过程在短短4天内，“熬夜”的成年小鼠中有80%死亡，死亡时间在睡眠剥夺开始后的72-96小时不等。在死亡之前，这些小鼠表现出平衡能力的丧失，以及对轻触刺激的反应极小或几乎没有。对去世的小鼠进行全身病理分析显示，“熬夜”的打击是全身性、多系统的！多个器官组织受到了损伤，包括7/8的肝脏组织坏死伴随炎症细胞浸润、1/2的脾脏的髓质边界模糊、3/8的肺表现出急性损伤、1/4的肠道结构损伤以及1/8的肾脏出现了病变。即使侥幸存活下来，“熬夜”的小鼠也出现了明显的生化改变。与对照组相比，暴露于CPW的小鼠表现出更高水平的血清丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）以及尿素。睡眠剥夺情况下多器官受到损伤为了明确长期睡眠剥夺诱导的多器官功能障碍（MODS）早期表型，研究者对“熬夜”48小时的小鼠进行了全面的病理检查。与先前开展的研究一致，研究者在睡眠剥夺小鼠中观察到ROS的积累；正如前文提到的那样，ROS是重要的信号分子和炎症标志物，可能会诱发睡眠不足引起的死亡。但令人惊讶的是，当研究者使用抗氧化剂中和ROS之后，无法阻止睡眠剥夺诱导的MODS的发生，暴露于CPW的小鼠依然会走向死亡。可见，长时间地熬夜，不仅是单一途径地“通过积累ROS而导致死亡”，一定还有其他途径/通路的存在，比如：通过诱发全身炎症反应，进而导致MODS的发生并最终死亡。进一步的观察发现，长时间睡眠剥夺的小鼠表现出器官损伤和炎症细胞浸润；再鉴于人体中观察到的情况——随着促炎细胞因子的过度释放，这种细胞因子风暴往往会导致器官损伤、疾病和死亡，于是，研究者陷入思考：小鼠体内是否也经历了细胞因子风暴，从而导致了死亡的发生呢？果不其然，随着熬夜的时间延长，小鼠体内的大多数促炎调节因子都随之上调，其中最主要的两种是IL-6和IL-17A。而这两种细胞因子均能介导人类细胞因子风暴的产生，尤其是IL-6被认为是这一过程的初始驱动因子。此外，促炎因子趋化因子（C-X-C基序）配体（CXCL1）和CXCL2也显著上调，而这些分子在中性粒细胞招募和渗出的过程中发挥着重要作用。总结来说，长时间的睡眠剥夺能够诱发促炎细胞因子的增加，且持续时间越长，释放出来的细胞因子数量也越大。随着细胞因子风暴在小鼠体内“席卷”，摧毁身体内多器官以及系统，最终导致疾病和死亡的发生。睡眠剥夺导致血液中促炎细胞因子的积累下一个要回答的问题便是：细胞因子风暴究竟是如何形成的？进一步的分析发现，睡眠剥夺会诱导PGD2在大脑中不断的积累，在ATP结合盒转运蛋白C4（ABCC4）转运体的介导下，PGD2能够通过血脑屏障被外排至血液中，导致循环中促炎细胞因子的过度产生，最终形成细胞因子风暴样综合症和MODS。这时候，如果能够阻断PGD2/PGD2受体1（DP1）轴，则能够显著减少睡眠剥夺诱发的全身炎症反应。睡眠剥夺诱发细胞因子风暴炎症反应的机制综上，不同于先前实验中提及的肠道ROS致死原理，来自清华大学的张二荃研究团队提出了一个“睡眠剥夺导致免疫崩溃甚至死亡”的全新机制——在搭建了有效的睡眠剥夺系统CPW之后，研究者发现长时间睡眠剥夺会诱导PGD2在脑内的不断积累，在穿透血脑屏障并进入血液循环之后，会导致促炎细胞因子的过量产生，最终诱发一系列的器官损伤以及死亡。因此，“睡眠不足，免疫崩溃”是有科学依据的！睡眠的重要性不言而喻，不如就从今天开始拔起“早睡”的flag吧。参考资料： Sang D, Lin K, Yang Y, Ran G, Li B, Chen C, Li Q, Ma Y, Lu L, Cui XY, Liu Z, Lv SQ, Luo M, Liu Q, Li Y, Zhang EE. Prolonged sleep deprivation induces a cytokine-storm-like syndrome in mammals. Cell. 2023 Dec 7;186(25):5500-5516.e21. doi: 10.1016/j.cell.2023.10.025. Epub 2023 Nov 27. PMID: 38016470. 撰文 | Swagpp 编辑 | Swagpp 来源 | 梅斯医学部分文字来源于网络，本文仅用于分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！精彩推荐： 1、最延寿的运动是它！中山大学最新研究：久坐、步行、剧烈运动都“加速衰老”？但这种运动能抗衰老 2、吃饭要吃「八分饱」！研究表明：吃八分饱不仅能延缓衰老，还不会损害免疫功能！PLA2G7是关键因子 3、神药“二甲双胍”究竟几分真假？多项研究表明：二甲双胍能够降血糖、抗衰老，但也会诱发诸多副作用，例如肝中毒、乳酸中毒 4、“下半身”或许真的可以思考？研究表明：睾丸竟是最像大脑的器官，基因高度相似，共享13,442种蛋白质 5、你站起身来会容易眼前发黑吗？研究表明：直立性低血压患心血管疾病和痴呆的风险会升高，且症状出现得越早，认知衰退风险越高！点击下方「阅读原文」，前往生物谷官网查询更多生物相关资讯~

临床研究临床结果

2024-09-18

·生物谷

晚讯｜全球有了第七位“治愈者”之后，人类距离治愈艾滋病还有多远？40亿元，江苏无锡成立生物医药产业专项母基金

1. 全球有了第七位“治愈者”之后，人类距离治愈艾滋病还有多远？全球第七位艾滋病“治愈者”出现，但现有疗法多数只能抑制HIV复制，无法彻底清除。干细胞移植虽成功治愈7人，但难普适且有并发症风险。科学家正研发靶向HIV的基因疗法，为治愈艾滋病带来新希望。 2. 40亿元，江苏无锡成立生物医药产业专项母基金江苏无锡设立40亿元生物医药产业专项母基金，由多方共同出资，主要投向创新药、高端原料药、医疗器械等领域，为江苏省战略性新兴产业母基金的一环。 3. 市值4000亿，港股“巨无霸”IPO来了美的集团启动港股招股，集资额约312亿港元，将实现A+H双上市，且医疗业务成为其第二增长曲线，旗下五大医疗业务板块构建完整医疗服务链。 4. 同靶点2款新药获批，9款临床3期，国产自免比PD-1还卷中国批准两款国产IL-17A单抗药物上市，打破进口药垄断，银屑病药物市场快速增长，多款国产药物处于临床3期，预计未来将迎来激烈竞争。IL-17药物成为重要治疗方法，生物类似药市场份额将提升。 5. 科伦药业地屈孕酮片获得药品注册批准科伦药业宣布其化学药品地屈孕酮片近日获得国家药监局注册批准，为国产前三家，将增强公司在生殖健康领域竞争力。该药已在多国上市，用于治疗孕酮不足相关疾病。 6. 湖北杀出一匹生物技术黑马：获武汉上市公司投资新纵科病毒获爱博泰克149.927万元投资，占比增至20.9248%，加强病毒疾病工程技术研发。本文仅用于学术分享，转载请注明出处。若有侵权，请联系微信：bioonSir 删除或修改！

临床3期基因疗法上市批准IPO生物类似药