Drugs最新文献

{"title":"Moderate-Intensity Statin Plus Ezetimibe: Time to Rethink it as an Optimal Initial Lipid-Lowering Strategy.","authors":"Sha Li, Hui-Hui Liu, Jian-Jun Li","doi":"10.1007/s40265-024-02113-5","DOIUrl":"10.1007/s40265-024-02113-5","url":null,"abstract":"<p><p>Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"51-65"},"PeriodicalIF":13.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616733","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}

{"title":"Xanomeline/Trospium Chloride: First Approval.","authors":"Yahiya Y Syed","doi":"10.1007/s40265-024-02126-0","DOIUrl":"10.1007/s40265-024-02126-0","url":null,"abstract":"<p><p>Xanomeline/trospium chloride (COBENFY™), formerly KarXT, is a first-in-class, oral, fixed-dose muscarinic agonist/antagonist combination being developed for use in schizophrenia and Alzheimer's disease psychosis. Xanomeline is thought to confer efficacy by acting as an agonist at M₁ and M₄ muscarinic acetylcholine receptors in the brain, and trospium chloride reduces the peripheral cholinergic adverse events associated with xanomeline. Xanomeline/trospium chloride received its first approval on 26 September 2024 in the USA for the treatment of schizophrenia in adults. This article summarizes the milestones in the development of xanomeline/trospium chloride leading to this first approval for schizophrenia.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"103-109"},"PeriodicalIF":13.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881702","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}

{"title":"Update on Mpox Management: Epidemiology, Vaccines and Therapeutics, and Regulatory Changes.","authors":"Youssef Rizk, Giuseppe Lippi, Brandon M Henry, Kin Israel Notarte, John G Rizk","doi":"10.1007/s40265-024-02117-1","DOIUrl":"10.1007/s40265-024-02117-1","url":null,"abstract":"<p><p>Mpox, caused by the monkeypox virus (MPXV), is categorized into two primary clades: Clade I and Clade II, with notable outbreaks linked to Clade IIb. Historically endemic in Africa, recent years have seen significant global spread. The World Health Organization (WHO) declared mpox a Public Health Emergency of International Concern in August 2024, highlighting the emergence of Clade Ib outside Africa and the broadening demographic impact of the outbreak. This review updates the current status of mpox vaccines and treatments, including their safety and effectiveness. There are two US Food and Drug Administration (FDA)-approved vaccines for the prevention of mpox disease, Jynneos^TM and ACAM2000^®. The Jynneos^TM vaccine, recommended for high-risk individuals, has seen limited uptake despite its efficacy in preventing disease. Tecovirimat, while FDA-approved for smallpox and available in the European Union for mpox, has shown mixed results in recent trials, with new data suggesting limited effectiveness in Clade I infections and emergence of new mutations with resistance to this drug. Brincidofovir and Vaccinia Immune Globulin Intravenous offer additional treatment options, particularly for severe cases, although their use is constrained by regulatory and logistical challenges. Furthermore, the WHO recently approved the first commercial molecular assay, the Alinity m MPXV assay by Abbott Molecular Inc., for emergency use-an essential step in expanding testing capacity in regions experiencing mpox outbreaks. These updates underscore the critical need for continued research to enhance therapeutic outcomes and adapt public health strategies. Ensuring equitable access to vaccines, treatments, and diagnostics remains a significant challenge as the global community responds to the evolving mpox situation.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1-9"},"PeriodicalIF":13.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575624","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}

{"title":"Effectiveness of Interventions to Reduce Opioid Use After Orthopaedic Surgery: A Systematic Review of Randomised Controlled Trials.","authors":"Melanie Hamilton, Stephanie Mathieson, Masoud Jamshidi, Andy Wang, Yi-Ching Lee, Danijela Gnjidic, Chung-Wei Christine Lin","doi":"10.1007/s40265-024-02116-2","DOIUrl":"https://doi.org/10.1007/s40265-024-02116-2","url":null,"abstract":"<p><strong>Background: </strong>The prescribing of opioids to patients for postoperative pain can lead to persistent opioid use. This review investigated the effectiveness of interventions aimed at reducing opioid use in patients after orthopaedic surgery.</p><p><strong>Methods: </strong>Electronic databases were searched from inception to November 2023. We included randomised controlled trials investigating interventions aimed at reducing opioid use after orthopaedic surgery. Two reviewers conducted the screening and data extraction and assessed the risk of bias (Cochrane Risk of Bias tool) and certainty of evidence (GRADE). The primary outcome was the mean daily dose of opioid analgesic medications in the medium term (1-3 months after randomisation). Results were pooled in a meta-analysis using a random-effects model where appropriate (e.g. I² < 50%) or summarised narratively.</p><p><strong>Results: </strong>The search yielded 17,471 records, of which 39 trials were included. High heterogeneity meant that most comparisons could not be pooled. The mean daily dose was lower with multimodal analgesia interventions than with placebo/no intervention/usual care or active control in the medium term. No between-group differences were found between other pharmacological or non-pharmacological interventions and either placebo/no intervention/usual care or active control at the medium-term time point. The certainty of evidence ranged from low to moderate.</p><p><strong>Conclusions: </strong>Multimodal analgesic interventions may reduce opioid use compared with placebo/no intervention/usual care or active control in the medium term. However, the high heterogeneity and low certainty of evidence means it is uncertain which interventions are effective in reducing opioid use after orthopaedic surgery.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863667","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}

{"title":"Enlonstobart: First Approval.","authors":"Matt Shirley","doi":"10.1007/s40265-024-02119-z","DOIUrl":"10.1007/s40265-024-02119-z","url":null,"abstract":"<p><p>Enlonstobart (Enshuxing^®), a recombinant, fully humanised immunoglobulin G4 monoclonal antibody targeted against programmed cell death protein 1 (PD-1), is being developed by the CSPC Pharmaceutical Group for the treatment of advanced cervical cancer and other solid tumours. Enlonstobart received its first approval (a conditional marketing authorisation) in June 2024, in China, for use in patients with recurrent or metastatic programmed cell death ligand 1 (PD-L1)-positive cervical cancer who have failed previous platinum-containing chemotherapy. Phase III clinical evaluation of enlonstobart for use as first-line treatment (in combination with chemotherapy ± bevacizumab) in patients with recurrent or metastatic PD-L1-positive cervical cancer is also underway in China. Additionally, phase II clinical development of enlonstobart (as a part of combination therapy) for use against a range of other solid tumour types is continuing. This article summarises the milestones in the development of enlonstobart leading to this first approval for recurrent or metastatic cervical cancer.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1659-1663"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667053","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}

{"title":"A Meta-analysis Exploring the Efficacy of Neuropathic Pain Medication for Low Back Pain or Spine-Related Leg Pain: Is Efficacy Dependent on the Presence of Neuropathic Pain?","authors":"Jennifer Ward, Anthony Grinstead, Amy Kemp, Paula Kersten, Annina B Schmid, Colette Ridehalgh","doi":"10.1007/s40265-024-02085-6","DOIUrl":"10.1007/s40265-024-02085-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;Highly variable pain mechanisms in people with low back pain or spine-related leg pain might contribute to inefficacy of neuropathic pain medication. This meta-analysis aimed to determine how neuropathic pain is identified in clinical trials for people taking neuropathic pain medication for low back pain or spine-related leg pain and whether subgrouping based on the presence of neuropathic pain influences efficacy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EMBASE, MEDLINE, Cochrane Central, CINAHL [EBSCO], APA PsycINFO, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry were searched from inception to 14 May, 2024. Randomized and crossover trials comparing first-line neuropathic pain medication for people with low back pain or spine-related leg pain to placebo or usual care were included. Two independent authors extracted data. Random-effects meta-analyses of all studies combined, and pre-planned subgroup meta-analyses based on the certainty of neuropathic pain (according to the neuropathic pain Special Interest Group [NeuPSIG] neuropathic pain grading criteria) were completed. Certainty of evidence was judged using the grading of recommendations assessment development and evaluation [GRADE] framework.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Twenty-seven included studies reported on 3619 participants. Overall, 33% of studies were judged unlikely to include people with neuropathic pain, 26% remained unclear. Only 41% identified people with possible, probable, or definite neuropathic pain. For pain, general analyses revealed only small effects at short term (mean difference [MD] - 9.30 [95% confidence interval [CI] - 13.71, - 4.88], I&lt;sup&gt;2&lt;/sup&gt; = 87%) and medium term (MD - 5.49 [95% CI - 7.24, - 3.74], I&lt;sup&gt;2&lt;/sup&gt; = 0%). Subgrouping at short term revealed studies including people with definite or probable neuropathic pain showed larger effects on pain (definite; MD - 16.65 [95% CI - 35.95, 2.65], I&lt;sup&gt;2&lt;/sup&gt; = 84%; probable; MD - 10.45 [95% CI - 14.79, - 6.12], I&lt;sup&gt;2&lt;/sup&gt; = 20%) than studies including people with possible (MD - 5.50 [95% CI - 20.52, 9.52], I&lt;sup&gt;2&lt;/sup&gt; = 78%), unlikely (MD - 6.67 [95% CI - 10.58, 2.76], I&lt;sup&gt;2&lt;/sup&gt; = 0%), or unclear neuropathic pain (MD - 8.93 [95% CI - 20.57, 2.71], I&lt;sup&gt;2&lt;/sup&gt; = 96%). Similarly, general analyses revealed negligible effects on disability at short term (MD - 3.35 [95% CI - 9.00, 2.29], I&lt;sup&gt;2&lt;/sup&gt; = 93%) and medium term (MD - 4.06 [95% CI - 5.63, - 2.48], I&lt;sup&gt;2&lt;/sup&gt; = 0%). Sub-grouping at short term revealed larger effects in studies including people with definite/probable neuropathic pain (MD - 9.25 [95% CI - 12.59, - 5.90], I&lt;sup&gt;2&lt;/sup&gt; = 2%) compared with those with possible/unclear/unlikely neuropathic pain (MD -1.57 [95% CI - 8.96, 5.82] I&lt;sup&gt;2&lt;/sup&gt; = 95%). Medium-term outcomes showed a similar trend, but were limited by low numbers of studies. Certainty of evidence was low to very low for all outcomes.","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1603-1636"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7616789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497072","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}

{"title":"Fulzerasib: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-024-02120-6","DOIUrl":"10.1007/s40265-024-02120-6","url":null,"abstract":"<p><p>Fulzerasib (Dupert^®; Innovent Biologics/GenFleet Therapeutics) is an orally active small molecule inhibitor of the KRAS G12C mutant protein being developed for the treatment of solid tumors harboring the KRAS G12C oncogenic driver mutation, including non-small cell lung cancer (NSCLC) and colorectal cancer. Fulzerasib received its first approval on 21 August 2024 in China, for the treatment of adults with KRAS G12C-mutated advanced NSCLC who have received at least one line of systemic therapy. This conditional approval was based on the positive results of a single-arm, phase II study. This article summarizes the milestones in the development of fulzerasib leading to this first approval for KRAS G12C-mutated advanced NSCLC.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1665-1671"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715669","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}

{"title":"The Utilization of the Accelerated Approval Pathway in Oncology: A Case Study of Pembrolizumab.","authors":"Robert Kester, Sunita Zalani, Scot Ebbinghaus, Eric Rubin","doi":"10.1007/s40265-024-02111-7","DOIUrl":"10.1007/s40265-024-02111-7","url":null,"abstract":"<p><p>The accelerated approval (AA) pathway was established by the United States Food and Drug Administration (FDA) to provide earlier access to therapies for patients with serious medical conditions and unmet medical needs. Since its inception, the AA pathway has been used for novel treatments across different therapeutic areas, but most prominently in oncology, including the immune checkpoint inhibitor class. This review article describes the history of regulatory approvals for pembrolizumab, an immunotherapy agent targeting programmed death receptor-1 (PD-1), and use of the AA pathway and the corresponding regulatory decisions made by the FDA. From its first AA in September 2014 to February 2024, pembrolizumab has used the accelerated pathway for roughly 40% of the approved indications listed in the US Prescribing Information and was the first oncology therapy to receive an AA for an alternate dosing regimen and a tissue-agnostic indication. As of February 2024, 14 of the 18 indication-specific AAs and 1 post-marketing requirement (PMR) for the alternate dosing regimen AA were converted to traditional approvals. Accelerated approvals for two indications were withdrawn, and the remaining ongoing PMRs are not due until later in 2024 or 2025. The median conversion time from AA to traditional approval was 2.6 years, which is roughly 6 months earlier than the median time reported for oncology AAs. While FDA was the first agency to establish an expedited approval pathway, regulators from other countries have established similar pathways. For pembrolizumab, approximately half of the datasets that supported US AAs also supported expedited approval, or sometimes full approval, in Canada, EU, Australia or Japan. Ultimately, the AA pathway balances the provision of earlier access to therapies with overcoming uncertainty about potential effectiveness, and therefore it is important to confirm treatment benefit and withdraw indications that do not confirm benefit in a timely manner. The regulatory strategy and use of this expedited program for pembrolizumab highlights the importance of the AA pathway in providing oncology patients with earlier access to life-saving medications.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1579-1601"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616734","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}

{"title":"Odronextamab: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-024-02112-6","DOIUrl":"10.1007/s40265-024-02112-6","url":null,"abstract":"<p><p>Odronextamab (Ordspono^™), a CD20xCD3 bispecific antibody, is being developed by Regeneron Pharmaceuticals for the treatment of B-cell non-Hodgkin's lymphoma. On 26 August 2024, odronextamab received its first approval in the EU as monotherapy for the treatment of adult patients with relapsed/refractory follicular lymphoma (FL) or relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after ≥ 2 lines of systemic therapy. Clinical trials in various other B-cell non-Hodgkin's lymphoma, including mantle cell lymphoma, marginal zone lymphoma and chronic lymphocytic leukaemia, are underway in multiple countries. This article summarizes the milestones in the development of odronextamab leading to this first approval for the treatment of adult patients with relapsed/refractory FL or relapsed/refractory DLBCL.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1651-1658"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667054","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}

{"title":"Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review.","authors":"C Omar F Kamlin, Timothy M Jenkins, Jamie L Heise, Naseem S Amin","doi":"10.1007/s40265-024-02099-0","DOIUrl":"10.1007/s40265-024-02099-0","url":null,"abstract":"<p><p>Trientine tetrahydrochloride (TETA-4HCl, Cuvrior^®) is a copper chelating agent with the active moiety triethylenetetramine (trientine), developed by Orphalan, Inc. to address the unmet needs in the treatment of Wilson disease. The journey from bench to bedside builds upon the documented safety profile of trientine hydrochloride capsules developed initially to meet the needs of individuals intolerant to D-penicillamine (DPA). Trientine hydrochloride capsules are inherently unstable requiring strict cold chain storage conditions from production, transportation, and use at home by the patient. Trientine tetrahydrochloride has a distinctive, patent-protected unique polymorphic form, which permits the production at scale of film-coated scored tablets deemed room temperature stable for 36 months. Trientine tetrahydrochloride is supported by a well-characterized pharmacodynamic, pharmacokinetic, and metabolic profile demonstrating reliable and predictable dose linearity and dose proportionality kinetics. Trientine tetrahydrochloride is the only trientine formulation that has been compared with DPA in a prospective randomized clinical trial, demonstrating non-inferiority to DPA in adults with stable Wilson disease. On 28 April, 2022, the US Food and Drug Administration approved TETA-4HCl for use in adult patients with Wilson disease who are de-coppered and tolerant to DPA. Health authorities in multiple countries worldwide have approved TETA-4HCl for the treatment of adults and children aged 5 years or more who are intolerant to DPA including the European Union, UK, Saudi Arabia, Switzerland, Colombia, Australia, New Zealand, and China. This article aims to provide a comprehensive narrative review of the key milestones in the development of TETA-4HCl.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1509-1518"},"PeriodicalIF":13.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460701","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}