Vladimir Tesar, Jan Miroslav Hartinger, Zdenka Hruskova
{"title":"Avacopan as an add-on therapy for ANCA-associated vasculitis: a pharmacological overview.","authors":"Vladimir Tesar, Jan Miroslav Hartinger, Zdenka Hruskova","doi":"10.1080/17512433.2024.2432500","DOIUrl":"10.1080/17512433.2024.2432500","url":null,"abstract":"<p><strong>Introduction: </strong>ANCA-associated vasculitis (AAV) is a rare, life-threatening disease which may result in serious pulmonary and kidney damage. Cyclophosphamide or rituximab and high-dose glucocorticoids significantly improved patient outcomes, but at the expense of severe complications. Moreover, many patients still relapse and bear a significant burden of both disease- and treatment-related complications. Alternative complement pathway and C5a receptor signaling were demonstrated to play an important role in AAV pathogenesis. Avacopan is selective C5a receptor inhibitor successfully tested in renal AAV as glucocorticoid-sparing agent.</p><p><strong>Areas covered: </strong>Pharmacokinetic/pharmacodynamic properties, clinical efficacy and safety of avacopan, available clinical trials and real-world experience with avacopan.</p><p><strong>Expert opinion: </strong>In the phase 3 trial avacopan was shown to be non-inferior at six and superior at 12 months compared to high-dose glucocorticoids and either cyclophosphamide or rituximab in patients with active AAV. Treatment with avacopan was well tolerated and associated with improved quality of life. In patients with severe renal AAV, renal function improved more in avacopan-treated than in high-dose glucocorticoid-treated patients. Avacopan could thus replace high-dose glucocorticoids to avoid glucocorticoid-related toxicity and to improve long term renal outcome. As avacopan is CYP 3A4 inhibitor and substrate, drug-drug interactions must be considered during the treatment.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1099-1113"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune checkpoint inhibition of metastatic melanoma: achieving high efficacy in the face of high toxicity.","authors":"Joy Justice, Roma A Kankaria, Douglas B Johnson","doi":"10.1080/17512433.2024.2431513","DOIUrl":"10.1080/17512433.2024.2431513","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) have advanced the treatment of metastatic melanoma by blocking immune system down-regulators enhancing T-cell-mediated anti-tumor responses. However, many ICIs induce immune-related adverse effects (irAEs) that can impact many organ systems.</p><p><strong>Areas covered: </strong>Strategies used to manage irAEs include corticosteroids, anti-tumor necrosis factor alpha (TNF-α) agents, other biological therapies, fecal microbiota transplantation (FMT), and emerging regimens. In this review, we describe current evidence for the efficacy of ICIs, acute and chronic immune toxicities, and strategies to manage toxicities for patients treated with ICIs.</p><p><strong>Expert opinion: </strong>IrAE management will likely evolve by developing more tailored approaches to prevent toxicities, improving non-steroidal management strategies and tailoring the dose of steroids, and identifying biomarkers of severe toxicities.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1115-1125"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methenamine Hippurate in UTI management: a reemerging pharmacological strategy.","authors":"Mehwash Nadeem, Hashim Hashim","doi":"10.1080/17512433.2024.2445621","DOIUrl":"10.1080/17512433.2024.2445621","url":null,"abstract":"","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1095-1098"},"PeriodicalIF":3.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marta Waliszewska-Prosół, Bianca Raffaelli, Marcin Straburzyński, Paolo Martelletti
{"title":"Understanding the efficacy and tolerability of migraine treatment: a deep dive into CGRP antagonists.","authors":"Marta Waliszewska-Prosół, Bianca Raffaelli, Marcin Straburzyński, Paolo Martelletti","doi":"10.1080/17512433.2024.2417655","DOIUrl":"10.1080/17512433.2024.2417655","url":null,"abstract":"<p><strong>Introduction: </strong>The discovery of the role of the calcitonin gene-related peptide (CGPR) in migraine pathogenesis ushered in a new era in headache medicine. This evidence led to the development of small-molecule CGRP receptor antagonists and monoclonal antibodies targeting either CGRP or its receptor.</p><p><strong>Areas covered: </strong>We will present selected aspects of the role of CGRP in the pathogenesis of migraine, the efficacy of CGRP-targeted treatment, and the still-open questions regarding the practical application of CGRP antagonists in headache medicine.</p><p><strong>Expert opinion: </strong>CGRP-targeting drugs represent a transformative approach to migraine treatment, offering superior efficacy and tolerability compared to traditional therapies, they are a helpful addition to the treatment arsenal but also have their flaws and require further observation. Their availability provides new hope for migraine patients, particularly those who have not responded adequately to conventional treatments. Future directions for migraine care planning, especially for chronic migraine and medication-overuse headache, should include universal access to these specific and effective forms of therapy to prevent complications from the disease and its negative effects in many aspects of a patient's life.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1039-1051"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zonghao Pan, Muhammad Adnan Zaman, Sidra Kalsoom, Yani Zhang
{"title":"Messenger interference RNA therapies targeting apolipoprotein C-III and angiopoietin-like protein 3 for mixed hyperlipidemia: the future of plozasiran and zodasiran.","authors":"Zonghao Pan, Muhammad Adnan Zaman, Sidra Kalsoom, Yani Zhang","doi":"10.1080/17512433.2024.2423724","DOIUrl":"10.1080/17512433.2024.2423724","url":null,"abstract":"<p><strong>Introduction: </strong>Mixed hyperlipidemia represents a substantial public health issue and a considerable burden on healthcare systems. Although the introduction of statins and LDL-cholesterol lowering agents have significantly reduced the incidence of atherosclerotic cardiovascular diseases (ASCVD), a significant portion of the population continues to exhibit ASCVD progression due to elevated triglyceride-rich lipoprotein (TRL) levels. This persistent risk has catalyzed the development of novel pharmacological interventions targeting these lipoproteins.</p><p><strong>Areas covered: </strong>Our special report commenced with a targeted PubMed search using keywords such as 'plozasiran,' 'zodasiran,' and terms related to APOC3 and ANGPTL3. As the review progressed, emergent research questions guided further searches, allowing for the inclusion of additional relevant articles to comprehensively illustrate the linkage between TRLs and cardiovascular disease, discuss the roles of APOC3, ANGPTL3, and the pharmaceutical agents that target these proteins, and provide a comparison on the ARCHES-2 and MUIR trials.</p><p><strong>Expert opinion: </strong>The ARCHES-2 and MUIR trials demonstrated effective triglyceride reduction by these therapies, yet it is uncertain if this correlates with significant clinical benefits. Advances in antisense oligonucleotide technology, especially the GalNAc delivery platform, show promise for personalized lipid management, though challenges such as cost and safety concerns remain.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1017-1023"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire!","authors":"Djordje S Popovic, Dimitrios Patoulias, Theocharis Koufakis, Paschalis Karakasis, Ieva Ruža, Nikolaos Papanas","doi":"10.1080/17512433.2024.2418398","DOIUrl":"10.1080/17512433.2024.2418398","url":null,"abstract":"<p><p>Tobacco use represents the leading preventable risk factor for premature deaths worldwide. A meta-analysis of 74 epidemiological studies, including 3.2 million individuals with type 2 diabetes mellitus (T2DM) from 33 countries, reported a pooled prevalence of smoking of 20.8% among individuals with T2DM. Cigarette smoking further aggravates existing deleterious vascular effects of T2DM. Namely, chronic hyperglycemia and exposure to cigarette smoke cause additive injurious effect on the endothelium, leading to an acceleration of vascular complications seen in persons with T2DM and tobacco use disorders (TUD). In a recent study, Wang and colleagues found that semaglutide use was associated with a significantly lower risk for medical encounters for TUD, when compared to other antidiabetic drug classes; indeed, this effect was strongest compared with insulins and weakest compared with other glucagon-like peptide-1 receptor agonists. Semaglutide was associated with reduced smoking cessation medication prescriptions and counseling. Similar findings were observed irrespective of the presence of obesity. Therefore, semaglutide use might be useful in terms of smoking cessation among individuals with T2DM, thus offering an additional benefit for this constantly growing population. However, those interesting findings should be confirmed through dedicated, large-scale randomized controlled trials.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1009-1012"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Enmin Xie, Shuoyan An, Yaxin Wu, Zixiang Ye, Xuecheng Zhao, Yike Li, Nan Shen, Yanxiang Gao, Jingang Zheng
{"title":"Renin-angiotensin system inhibition and mortality in patients undergoing dialysis with coronary artery disease: insights from a multi-center observational study.","authors":"Enmin Xie, Shuoyan An, Yaxin Wu, Zixiang Ye, Xuecheng Zhao, Yike Li, Nan Shen, Yanxiang Gao, Jingang Zheng","doi":"10.1080/17512433.2024.2419915","DOIUrl":"10.1080/17512433.2024.2419915","url":null,"abstract":"<p><strong>Background: </strong>While the survival benefits of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are firmly established in the general population, their efficacy within patient undergoing dialysis with coronary artery disease (CAD) remains controversial.</p><p><strong>Methods: </strong>Between January 2015 and June 2021, 1168 patients undergoing dialysis with CAD were assessed from 30 tertiary medical centers. The primary outcome was all-cause death, and the secondary outcome was cardiovascular death. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for between-group differences.</p><p><strong>Results: </strong>Overall, ACEI or ARB were prescribed to 518 patients (44.3%) upon discharge. After a median follow-up of 22.2 months, 361 (30.9%) patients died, including 243 cardiovascular deaths. The use of ACEI or ARB was associated with a significantly lower risk of all-cause (25.3% vs 35.4%, hazard ratio [HR] 0.65, 95% confidence interval [CI] 0.52-0.82, <i>p</i> < 0.001) and cardiovascular death (17.0% vs 23.8%; HR 0.64, 95% CI 0.48-0.83, <i>p</i> = 0.001). These findings remained consistent across IPTW and PSM analyses. Sensitivity analyses for ACEI and ARB use separately yielded similar results.</p><p><strong>Conclusions: </strong>Our findings suggested that among patients undergoing dialysis with CAD, ACEI or ARB use was associated with a lower risk of all-cause and cardiovascular death.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1053-1062"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142461438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Population pharmacokinetics of nirmatrelvir/ritonavir in critically ill Chinese COVID-19 patients and recommendations for medication use: a two-center retrospective study.","authors":"Junjun Xu, Jinmeng Li, Meng Chen, Huifang Jiang, Xudong Fan, Yangmin Hu, Haili Shan, Mingdong Yang, Yichao Xu, Yuying Lang, Haibin Dai, Xinjun Cai","doi":"10.1080/17512433.2024.2410385","DOIUrl":"10.1080/17512433.2024.2410385","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to establish population pharmacokinetics (PPK) models of nirmatrelvir/ritonavir in critically ill Chinese patients with the coronavirus disease 2019 (COVID-19) infection, explore factors affecting the pharmacokinetics (PK) of nirmatrelvir/ritonavir.</p><p><strong>Methods: </strong>A total of 285 serum samples and clinical data were collected from 152 patients. The PPK models of nirmatrelvir/ritonavir were analyzed using nonlinear mixed-effect modeling (NONMEM) approach. The optimal dosing regimen for patients with different renal function was determined using Monte Carlo simulations.</p><p><strong>Results: </strong>The population typical values of apparent clearance (CL/F) and apparent volume of distribution (V/F) of nirmatrelvir were 2.26 L/h and 15.3 L, respectively. Notably, creatinine clearance (CrCL) significantly influenced the PK variation of nirmatrelvir. Monte Carlo simulations suggested that patients with mild-to-moderate renal impairment experienced a 22.0-59.9% increase in the area under the curve (AUC) when they were administered a standard dose of nirmatrelvir compared to those with normal renal function. The AUC in patients with severe renal impairment after administration of 150 mg q12h nirmatrelvir was similar to that in patients with normal renal function after administration of 300 mg q12h nirmatrelvir.</p><p><strong>Conclusions: </strong>PPK modeling and simulation provided a reference for the rational clinical application of nirmatrelvir/ritonavir in critically ill Chinese patients.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1071-1079"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Muhammad Imtiaz, Muhammad Adnan Zaman, Abeel Naseer, Sidra Kalsoom
{"title":"Role of tenecteplase in ischemic stroke after 4.5 hours: an evaluation of the TRACE-III trial.","authors":"Muhammad Imtiaz, Muhammad Adnan Zaman, Abeel Naseer, Sidra Kalsoom","doi":"10.1080/17512433.2024.2427078","DOIUrl":"10.1080/17512433.2024.2427078","url":null,"abstract":"<p><p>Tenecteplase (TNK), as a thrombolytic treatment for acute ischemic stroke (AIS), has been found to be effective when used within 4.5 hours of symptom onset. However, the efficacy of TNK after 4.5 hours is not well established, especially in patients with large vessel occlusion and with no access to thrombectomy. In this article, we will discuss the results of the recently published TRACE-III trial. The study involved 516 patients with large vessel occlusion, either proximal middle cerebral artery or internal carotid artery, with salvageable brain tissue and no endovascular thrombectomy access. Key safety outcomes included symptomatic intracranial hemorrhage and death. TNK treatment resulted in a higher percentage of patients with a modified Rankin scale score of 0 or 1 at 90 days than standard medical treatment. Mortality at 90 days was 13.3% with TNK and 13.1% with standard medical treatment. The trial found that TNK treatment for Chinese patients with ischemic stroke resulted in less disability and similar survival compared to standard medical treatment. However, there was a higher incidence of symptomatic intracranial hemorrhage within 36 hours.</p>","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"1013-1016"},"PeriodicalIF":3.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prophylaxis and treatment of acute intraocular pressure rise after cataract surgery: considerations to aid in decision-making.","authors":"Eitan A Katz, Shivani Majmudar, Ahmad A Aref","doi":"10.1080/17512433.2024.2427104","DOIUrl":"10.1080/17512433.2024.2427104","url":null,"abstract":"","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"995-997"},"PeriodicalIF":4.3,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142580974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}