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Emerging Biologic Therapies for the Treatment of Atopic Dermatitis. 治疗特应性皮炎的新兴生物疗法。
IF 13 1区 医学
Drugs Pub Date : 2024-10-04 DOI: 10.1007/s40265-024-02095-4
José Miguel Alvarenga, Thomas Bieber, Tiago Torres
{"title":"Emerging Biologic Therapies for the Treatment of Atopic Dermatitis.","authors":"José Miguel Alvarenga, Thomas Bieber, Tiago Torres","doi":"10.1007/s40265-024-02095-4","DOIUrl":"https://doi.org/10.1007/s40265-024-02095-4","url":null,"abstract":"<p><p>Atopic dermatitis (AD) is a prevalent inflammatory skin disease having a significant impact on patients' quality of life. Conventional treatments, including topical therapies and systemic immunosuppressants, often have limited efficacy and long-term safety concerns. Emerging biologic therapies target specific immune pathways implicated in AD pathogenesis, offering new therapeutic options in a disease known for its complex immune pathomechanisms. This review focuses on novel biologics under investigation, particularly those targeting specific immune pathways such as interleukin-4 (IL-4), IL-13, IL-22, IL-31, thymic stromal lymphopoietin (TSLP), and OX40-OX40L axis. Interleukin-4 and IL-13 inhibitors aim to reduce Th2-driven inflammation, while IL-22 inhibitors focus on restoring skin barrier function. Interleukin-31 inhibitors help alleviate pruritus, a major symptom in AD. OX40-OX40L pathway inhibitors can selectively suppress the activity of pathogenic T cells, without inducing significant immunosuppression. Bispecific antibodies targeting both IL-4 and IL-31 pathways are emerging as potential dual-action treatment for AD. Thymic stromal lymphopoietin inhibitors offer a novel strategy to control inflammation. While many of these therapies offer promising safety and efficacy profiles, long-term studies and real-world data are essential to confirm their lasting impact. This review highlights the potential of these emerging systemic therapies to continue transforming AD management and improve patient outcomes.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Donanemab: First Approval. 多奈单抗:首次批准。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1007/s40265-024-02087-4
Connie Kang
{"title":"Donanemab: First Approval.","authors":"Connie Kang","doi":"10.1007/s40265-024-02087-4","DOIUrl":"10.1007/s40265-024-02087-4","url":null,"abstract":"<p><p>Donanemab (donanemab-azbt; Kisunla<sup>TM</sup>) is an amyloid β-directed antibody developed by Eli Lilly and Company for the treatment of Alzheimer's disease. Donanemab recently received approval in the USA for the treatment of adults with early symptomatic Alzheimer's disease (patients with mild cognitive impairment or mild dementia stage of disease). This article summarizes the milestones in the development of donanemab leading to this first approval for Alzheimer's disease.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1313-1318"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management. 靶向鞘氨醇-1-磷酸途径:炎症性肠病治疗的新机遇。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-26 DOI: 10.1007/s40265-024-02094-5
Konstantina Kitsou, Georgios Kokkotis, Jesús Rivera-Nieves, Giorgos Bamias
{"title":"Targeting the Sphingosine-1-Phosphate Pathway: New Opportunities in Inflammatory Bowel Disease Management.","authors":"Konstantina Kitsou, Georgios Kokkotis, Jesús Rivera-Nieves, Giorgos Bamias","doi":"10.1007/s40265-024-02094-5","DOIUrl":"10.1007/s40265-024-02094-5","url":null,"abstract":"<p><p>Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC) are chronic immune-mediated diseases which primarily target the intestines. In recent years, the development and regulatory approval of various immunotherapies, both biological agents and small molecules, that target specific pathways of the IBD-associated inflammatory cascade have revolutionized the treatment of IBD. Small molecules offer the advantages of oral administration and short wash-out times. Sphingosine-1-phosphate (S1P) is a bioactive metabolite of ceramide, which exerts its functions after binding to five G-protein-coupled receptors (S1PR1-S1PR5). Concerning IBD, S1P participates in the egress of lymphocytes from the secondary lymphoid tissue and their re-circulation to sites of inflammation, mainly through S1PR1 binding. In addition, this system facilitates the differentiation of T-helper cells towards proinflammatory immunophenotypes. Recently, S1P modulators have offered a valuable addition to the IBD treatment armamentarium. They exert their anti-inflammatory function via sequestration of T cell subsets in the lymphoid tissues and prevention of gut homing. In this review, we revisit the role of the S1P/S1PR axis in the pathogenesis of IBD and discuss efficacy and safety data from clinical trials and real-world reports on the two S1PR modulators, ozanimod and etrasimod, that are currently approved for IBD treatment, and comment on their potential positioning in the IBD day-to-day management. We also present recent data on emerging S1P modulators. Finally, based on the successes and failures of S1PR modulators in IBD, we discuss future avenues of IBD treatments targeting the S1P/S1PR axis.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1179-1197"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of CYP2C19 Genotype Status on Clinical Outcomes in Patients with Symptomatic Coronary Artery Disease, Stroke, and Peripheral Arterial Disease: A Systematic Review and Meta-Analysis. CYP2C19 基因型状态对无症状冠心病、中风和外周动脉疾病患者临床结局的影响:系统回顾与元分析》。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-05 DOI: 10.1007/s40265-024-02076-7
Dominique P M S M Maas, Loes H Willems, Josephine Kranendonk, Cornelis Kramers, Michiel C Warlé
{"title":"Impact of CYP2C19 Genotype Status on Clinical Outcomes in Patients with Symptomatic Coronary Artery Disease, Stroke, and Peripheral Arterial Disease: A Systematic Review and Meta-Analysis.","authors":"Dominique P M S M Maas, Loes H Willems, Josephine Kranendonk, Cornelis Kramers, Michiel C Warlé","doi":"10.1007/s40265-024-02076-7","DOIUrl":"10.1007/s40265-024-02076-7","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Clopidogrel is widely used for the secondary prevention of atherothrombotic events in patients with coronary artery disease (CAD), ischemic stroke, and peripheral arterial disease (PAD). CYP2C19 plays a pivotal role in the conversion of clopidogrel to its active metabolite. Clopidogrel-treated carriers of a CYP2C19 loss-of-function allele (LOF) may have a higher risk of new atherothrombotic events. Previous studies on genotype-guided treatment were mainly performed in CAD and showed mixed results.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;To simultaneously investigate the impact of CYP2C19 genotype status on the rate of atherothrombotic events in the most common types of atherosclerotic disease (CAD, stroke, PAD).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A comprehensive search in Pubmed, EMBASE, and MEDLINE from their inception to July 23rd 2023 was performed. Randomized controlled trials (RCTs) comparing genotype-guided and standard antithrombotic treatment, and cohort studies and post hoc analyses of RCTs concerning the association between CYP2C19 genotype status and clinical outcomes in clopidogrel-treated patients were included. The primary efficacy endpoint was major adverse cardiovascular events (MACE) and the safety end point major bleeding. Secondary endpoints were myocardial infarction, stent thrombosis, and ischemic stroke.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Forty-four studies were identified: 11 studies on CAD, 29 studies on stroke, and 4 studies on PAD. In CAD, genotype-guided therapy significantly reduced the risk of MACE [risk ratio (RR) 0.60, 95% confidence interval (CI) 0.43-0.83], myocardial infarction (RR 0.53, 95% CI 0.42-0.68), and stent thrombosis (RR 0.64, 95% CI 0.43-0.94), compared with standard antithrombotic treatment. The rate of major bleeding did not differ significantly (RR 0.93, 95% CI 0.70-1.23). Most RCTs were performed in patients after percutaneous coronary intervention (9/11). In stroke, LOF carriers had a significantly higher risk of MACE (RR 1.61, 95% CI 1.25-2.08) and recurrent ischemic stroke (RR 1.89, 95% CI 1.48-2.40) compared with non-carriers. No significant differences were found in major bleeding (RR 0.90, 95% CI 0.43-1.89). In the 6955 patients with symptomatic PAD treated with clopidogrel in the EUCLID trial, no differences in MACE or major bleeding were found between LOF carriers and non-carriers. In three smaller studies on patients with PAD treated with clopidogrel after endovascular therapy, CYP2C19 genotype status was significantly associated with atherothrombotic events.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Genotype-guided treatment significantly decreased the rate of atherothrombotic events in patients with CAD, especially after PCI. In patients with history of stroke, LOF carriers treated with clopidogrel had a higher risk of MACE and recurrent stroke. The available evidence in PAD with regard to major adverse limb events is too limited to draw meaningful conclusions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1275-1297"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Long-Term Safety and Efficacy Evaluation of Travoprost Intracameral Implant Based on Pooled Analyses from Two Phase III Trials. 基于两项 III 期试验的汇总分析,对曲伏前列素巩膜内植入物进行长期安全性和有效性评估。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-06 DOI: 10.1007/s40265-024-02074-9
I Paul Singh, John P Berdahl, Steven R Sarkisian, Lilit A Voskanyan, Robert E Ang, Long V Doan, David Applegate, Yannan Shen, L Jay Katz, Angela C Kothe, Tomas Navratil
{"title":"Long-Term Safety and Efficacy Evaluation of Travoprost Intracameral Implant Based on Pooled Analyses from Two Phase III Trials.","authors":"I Paul Singh, John P Berdahl, Steven R Sarkisian, Lilit A Voskanyan, Robert E Ang, Long V Doan, David Applegate, Yannan Shen, L Jay Katz, Angela C Kothe, Tomas Navratil","doi":"10.1007/s40265-024-02074-9","DOIUrl":"10.1007/s40265-024-02074-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aim: &lt;/strong&gt;The purpose of this study was to conduct and interpret a pooled 12-month analysis of two prospective, multi-center, randomized, double-masked, controlled trials designed to assess the efficacy and safety of the travoprost intracameral implant (slow-eluting [SE] implant in development as a new therapeutic and fast-eluting [FE] implant included for masking purposes) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Subjects with OAG or OHT, on 0-3 intraocular pressure (IOP)-lowering medications, baseline unmedicated mean diurnal IOP of ≥ 21 mmHg, and IOP ≤ 36 mmHg at each baseline diurnal timepoint, received either a travoprost implant and twice-daily (BID) placebo eye drops or BID timolol 0.5% eye drops and a sham procedure. Subjects were followed through 12 months and assessed for IOP, reduction in topical IOP-lowering medications, and safety parameters including treatment-emergent adverse events (TEAEs). IOP at 8AM was prospectively collected at all study visits through 12 months and diurnal IOP, measured at 8AM, 10AM, and 4PM, was prospectively collected at baseline, day 10, week 6, and months 3 and 12.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 1150 subjects were randomized (385 FE implant, 380 SE implant, and 385 sham/timolol) across the two trials. Statistical non-inferiority to timolol and clinically relevant reductions in 8AM IOPs were demonstrated at month 12. In more detail, both implant groups demonstrated statistical non-inferiority to timolol and clinically relevant reductions from baseline in mean diurnal IOP at all visits over the 12-month evaluation period when diurnal IOP was collected. Additionally, both implant groups demonstrated robust treatment effect based on 8AM average IOP from day 10 through the specified visit which ranged from day 10 to month 12 from 6.9 to 8.5 mmHg in the FE implant group; 6.8 to 8.5 mmHg in the SE implant group; and 7.3 to 7.5 mmHg in the sham/timolol group. With regards to reduction in topical pharmacotherapy, at month 12, 77.6% of FE and 81.4% of SE implant eyes were completely free of all topical IOP-lowering medications and a significantly greater proportion of FE and SE implant eyes (89.9% and 93.0%) versus sham/timolol eyes (66.9%) were on the same or fewer topical IOP-lowering medications compared with pre-study (p &lt;  0.0001). Furthermore, of subjects on topical IOP medications at screening, a significantly greater proportion of FE implant (80.2%) and SE implant (85.1%) eyes versus sham/timolol (22.8%) eyes were on fewer topical IOP-lowering medications at month 12 compared with pre-study (p &lt;  0.0001). Lastly, of SE implant eyes on same or fewer topical IOP-lowering medications at month 12, the average through month 12 decreased by 0.9 medications, and of those SE implant eyes on fewer topical IOP-lowering medications compared with pre-study, the average through month 12 decreased by 1.4 medications. The most commo","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1299-1311"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anticoagulation in Chronic Kidney Disease. 慢性肾脏病的抗凝治疗。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-08-09 DOI: 10.1007/s40265-024-02077-6
Marco Montomoli, Boris Gonzales Candía, Adriana Acosta Barrios, Elisa Perez Bernat
{"title":"Anticoagulation in Chronic Kidney Disease.","authors":"Marco Montomoli, Boris Gonzales Candía, Adriana Acosta Barrios, Elisa Perez Bernat","doi":"10.1007/s40265-024-02077-6","DOIUrl":"10.1007/s40265-024-02077-6","url":null,"abstract":"<p><p>The nuanced landscape of anticoagulation therapy in patients with chronic kidney disease (CKD) presents a formidable challenge, intricately balancing the dual hazards of hemorrhage and thrombosis. These patients find themselves in a precarious position, teetering on the edge of these risks due to compromised platelet functionality and systemic disturbances within their coagulation frameworks. The management of such patients necessitates a meticulous approach to dosing adjustments and vigilant monitoring to navigate the perilous waters of anticoagulant therapy. This is especially critical considering the altered pharmacokinetics in CKD, where the clearance of drugs is significantly impeded, heightening the risk of accumulation and adverse effects. In the evolving narrative of anticoagulation therapy, the introduction of direct oral anticoagulants (DOACs) has heralded a new era, offering a glimmer of hope for those navigating the complexities of CKD. These agents, with their promise of easier management and a reduced need for monitoring, have begun to reshape the contours of care, particularly for patients not yet on dialysis. However, this is not without its caveats. The application of DOACs in the context of advanced CKD remains a largely uncharted territory, necessitating a cautious exploration to unearth their true potential and limitations. Moreover, the advent of innovative strategies such as left atrial appendage occlusion (LAAO) underscores the dynamic nature of anticoagulation therapy, potentially offering a tailored solution for those at the intersection of CKD and elevated stroke risk. Yet the journey toward integrating such advancements into standard practice is laden with unanswered questions, demanding rigorous investigation to illuminate their efficacy and safety across the spectrum of kidney disease. In summary, the management of anticoagulation in CKD is a delicate dance, requiring a harmonious blend of precision, caution, and innovation. As we venture further into this complex domain, we must build upon our current understanding, embracing both emerging therapies and the need for ongoing research. Only then can we hope to offer our patients a path that navigates the narrow strait between bleeding and clotting, toward safer and more effective care.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1199-1218"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Asthma and Cardiovascular Diseases: Navigating Mutual Pharmacological Interferences. 哮喘与心血管疾病:驾驭相互的药理干扰。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-26 DOI: 10.1007/s40265-024-02086-5
Mario Cazzola, Clive P Page, Nicola A Hanania, Luigino Calzetta, Maria Gabriella Matera, Paola Rogliani
{"title":"Asthma and Cardiovascular Diseases: Navigating Mutual Pharmacological Interferences.","authors":"Mario Cazzola, Clive P Page, Nicola A Hanania, Luigino Calzetta, Maria Gabriella Matera, Paola Rogliani","doi":"10.1007/s40265-024-02086-5","DOIUrl":"10.1007/s40265-024-02086-5","url":null,"abstract":"<p><p>Asthma and cardiovascular disease (CVD) often co-exist. When a patient has both conditions, management requires an approach that addresses the unique challenges of each condition separately, while also considering their potential interactions. However, specific guidance on the management of asthma in patients with CVD and on the management of CVD in patients with asthma is still lacking. Nevertheless, health care providers need to adopt a comprehensive approach that includes both respiratory and CVD health. The management of CVD in patients with asthma requires a delicate balance between controlling respiratory symptoms and minimising potential cardiovascular (CV) risks. In the absence of specific guidelines for the management of patients with both conditions, the most prudent approach would be to follow established guidelines for each condition independently. Careful selection of asthma medications is essential to avoid exacerbation of CV symptoms. In addition, optimal management of CV risk factors is essential. However, close monitoring of these patients is important as there is evidence that some asthma medications may have adverse effects on CVD and, conversely, that some CVD medications may worsen asthma symptoms. On the other hand, there is also increasing evidence of the potential beneficial effects of asthma medications on CVD and, conversely, that some CVD medications may reduce the severity of asthma symptoms. We aim to elucidate the potential risks and benefits associated with the use of asthma medications in patients with CVD, and the potential pulmonary risks and benefits for patients with asthma who are prescribed CVD medications.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1251-1273"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11512905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Donanemab: First Approval. 更正:多奈单抗:首次批准。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-10-15 DOI: 10.1007/s40265-024-02103-7
Connie Kang
{"title":"Correction: Donanemab: First Approval.","authors":"Connie Kang","doi":"10.1007/s40265-024-02103-7","DOIUrl":"10.1007/s40265-024-02103-7","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1335"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cefepime-Taniborbactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination. 头孢吡肟-他尼巴坦:新型头孢菌素/β-内酰胺酶抑制剂复方制剂
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-08-30 DOI: 10.1007/s40265-024-02082-9
George G Zhanel, Celine Mansour, Stacey Mikolayanko, Courtney K Lawrence, Sheryl Zelenitsky, Danyel Ramirez, Frank Schweizer, Denice Bay, Heather Adam, Philippe Lagacé-Wiens, Andrew Walkty, Neal Irfan, Nina Clark, David Nicolau, Carlo Tascini, James A Karlowsky
{"title":"Cefepime-Taniborbactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination.","authors":"George G Zhanel, Celine Mansour, Stacey Mikolayanko, Courtney K Lawrence, Sheryl Zelenitsky, Danyel Ramirez, Frank Schweizer, Denice Bay, Heather Adam, Philippe Lagacé-Wiens, Andrew Walkty, Neal Irfan, Nina Clark, David Nicolau, Carlo Tascini, James A Karlowsky","doi":"10.1007/s40265-024-02082-9","DOIUrl":"10.1007/s40265-024-02082-9","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Taniborbactam (formerly known as VNRX-5133) is a novel bicyclic boronate β-lactamase inhibitor of serine β-lactamases (SBLs) [Ambler classes A, C, and D] and metallo-β-lactamases (MBLs) [Ambler class B], including NDM and VIM, but not IMP. Cefepime-taniborbactam is active in vitro against most isolates of carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa (CRPA), including both carbapenemase-producing and carbapenemase-non-producing CRE and CRPA, as well as against multidrug-resistant (MDR), ceftazidime-avibactam-resistant, meropenem-vaborbactam-resistant, and ceftolozane-tazobactam-resistant Enterobacterales and P. aeruginosa. The addition of taniborbactam to cefepime resulted in a &gt; 64-fold reduction in MIC&lt;sub&gt;90&lt;/sub&gt; compared with cefepime alone for a 2018-2021 global collection of &gt; 13,000 clinical isolates of Enterobacterales. In the same study, against &gt; 4600 P. aeruginosa, a fourfold MIC reduction was observed with cefepime-taniborbactam, compared with cefepime alone. Whole genome sequencing studies have shown that resistance towards cefepime-taniborbactam in Enterobacterales arises due to the presence of multiple resistance mechanisms, often in concert, including production of IMP, PBP3 alterations, permeability (porin) defects, and upregulation of efflux pumps. In P. aeruginosa, elevated cefepime-taniborbactam MICs are also associated with the presence of multiple, concurrent mechanisms, most frequently IMP, PBP3 mutations, and upregulation of efflux pumps, as well as AmpC (PDC) overexpression. The pharmacokinetics of taniborbactam are dose proportional, follow a linear model, and do not appear to be affected when combined with cefepime. Taniborbactam's approximate volume of distribution (V&lt;sub&gt;d&lt;/sub&gt;) at steady state is 20 L and the approximate elimination half-life (t&lt;sub&gt;½&lt;/sub&gt;) is 2.3 h, which are similar to cefepime. Furthermore, like cefepime, taniborbactam is primarily cleared renally, and clearance corresponds with renal function. Pharmacodynamic studies (in vitro and in vivo) have reported that cefepime-taniborbactam has bactericidal activity against various β-lactamase-producing Gram-negative bacilli that are not susceptible to cefepime alone. It has been reported that antimicrobial activity best correlated with taniborbactam exposure (area under the curve). A phase III clinical trial showed that cefepime-taniborbactam (2 g/0.5 g administered as an intravenous infusion over 2 h) was superior to meropenem for the treatment of complicated urinary tract infection (cUTI), including acute pyelonephritis, caused by Enterobacterales species and P. aeruginosa while demonstrating similar safety compared with meropenem. The safety and tolerability of taniborbactam and cefepime-taniborbactam has been reported in one pharmacokinetic trial, and in two pharmacokinetic trials and one phase III clinical trial, respectively. Cefepime-taniborbactam appears to be well tolerated in both healthy su","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1219-1250"},"PeriodicalIF":13.0,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction: Zastaprazan: First Approval. 更正:Zastaprazan:首次批准。
IF 13 1区 医学
Drugs Pub Date : 2024-10-01 Epub Date: 2024-09-26 DOI: 10.1007/s40265-024-02093-6
Hannah A Blair
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