Drugs最新文献

{"title":"Ebronucimab: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-025-02146-4","DOIUrl":"10.1007/s40265-025-02146-4","url":null,"abstract":"<p><p>Ebronucimab (^®) is a subcutaneous fully human anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody being developed by Akeso Biopharma for the treatment of dyslipidaemia. In September 2024, ebronucimab was approved in China, in combination with statins or statins and other lipid-lowering therapies, for adult patients with primary hypercholesterolaemia [including heterozygous familial hypercholesterolaemia (HeFH)] and mixed hyperlipidaemia who are unable to achieve the low-density lipoprotein cholesterol target after receiving moderate or higher doses of statins. This article summarizes the milestones in the development of ebronucimab leading to this first approval for primary hypercholesterolaemia, mixed hyperlipidaemia and HeFH.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"437-441"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255051","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":"Treatment of Osteoporosis and Osteoarthritis in the Oldest Old.","authors":"Nicholas Fuggle, Andrea Laslop, René Rizzoli, Nasser Al-Daghri, Majed Alokail, Ewa Balkowiec-Iskra, Charlotte Beaudart, Olivier Bruyère, Angie Botto-van Bemden, Nansa Burlet, Etienne Cavalier, Francesca Cerreta, Manju Chandran, Antonio Cherubini, Mario Miguel Coelho da Silva Rosa, Philip Conaghan, Bernard Cortet, Alfonso Cruz Jentoft, Elizabeth M Curtis, Patrizia D'Amelio, Bess Dawson-Hughes, Elaine M Dennison, Mickaël Hiligsmann, Jean-Marc Kaufman, Stefania Maggi, Radmila Matijevic, Eugene McCloskey, Daniel Messina, Daniel Pinto, Maria Concepcion Prieto Yerro, Régis Pierre Radermecker, Yves Rolland, Carla Torre, Nicola Veronese, John A Kanis, Cyrus Cooper, Jean-Yves Reginster, Nicholas C Harvey","doi":"10.1007/s40265-024-02138-w","DOIUrl":"10.1007/s40265-024-02138-w","url":null,"abstract":"<p><p>Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"343-360"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448141","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":"Risperidone In Situ Microparticles: A Review in Schizophrenia.","authors":"Yahiya Y Syed","doi":"10.1007/s40265-024-02140-2","DOIUrl":"10.1007/s40265-024-02140-2","url":null,"abstract":"<p><p>Risperidone in situ microparticles (risperidone ISM^®) is a novel long-acting prolonged-release formulation approved in the EU and USA for treating schizophrenia in adults. Once-monthly intramuscular injections of risperidone ISM^® provide immediate and sustained therapeutic levels of risperidone, eliminating the need for loading doses or oral supplementation. In the pivotal PRISMA-3 trial in patients with acute schizophrenia exacerbation, risperidone ISM^® significantly improved Positive and Negative Syndrome Scale (primary endpoint) and Clinical Global Impression-Severity of Illness (key secondary endpoint) total scores over the 12-week double-blind phase, with improvements observed as early as day 8. Continued treatment sustained efficacy over the 12-month open-label extension phase. Risperidone ISM^® also improved social functioning and had a positive impact on health-related quality of life. Patients stable on daily oral risperidone maintained their treatment benefits after switching to monthly risperidone ISM^®. Risperidone ISM^® was generally well tolerated in clinical trials, with a safety profile consistent with that of oral risperidone. Its fast onset of action, without the need for oral supplementation or loading doses, makes risperidone ISM^® a promising long-acting injectable that could enhance treatment adherence.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"425-435"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390511","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":"Prospective 18-Month Study of Bimatoprost Intracameral Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension in US Clinical Practice.","authors":"Eric Mann, Jeffrey A Kammer, Gagan Sawhney, Jella An, Erica C Werts, Vanessa Vera, Marcos Rivas, Hongxin Lai, Sadhana Sonparote, E Randy Craven","doi":"10.1007/s40265-025-02157-1","DOIUrl":"10.1007/s40265-025-02157-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Bimatoprost implant 10 µg (Durysta) is an intracameral biodegradable implant that releases bimatoprost to lower intraocular pressure (IOP). The purpose of this study was to prospectively collect effectiveness and safety data after administration of the implant in patients with open-angle glaucoma or ocular hypertension.</p><p><strong>Methods: </strong>This phase IV, multicenter, prospective, observational, open-label, 18-month study (ARGOS) enrolled adult patients with open-angle glaucoma or ocular hypertension who were scheduled to receive the bimatoprost implant in one or both eyes. Data collected included IOP, use of topical IOP-lowering medications, treatment-emergent adverse events, and central corneal endothelial cell density. The primary endpoint was the proportion of primary (first-treated) eyes that received no additional (new) IOP-lowering treatment per standard medical care through month 6 after the implant administration.</p><p><strong>Results: </strong>A total of 217 patients (341 eyes) were enrolled, and 132 patients (60.8%) and 203 eyes (59.5%) completed the study. Most patients were on topical IOP-lowering medication before receiving the implant. After implant administration, the proportion of primary eyes that had received no additional treatment was 88.6% (95% confidence interval 86.6-90.6) at month 6 (primary endpoint) and remained high throughout the follow-up: 83.7% (95% confidence interval 80.2-87.3) at month 12 and 77.7% (95% confidence interval 73.4-82.1) at month 18. Intraocular pressure was reduced after implant administration, with mean changes in IOP from baseline at follow-up visits ranging from - 1.0 to - 2.0 mm Hg. The mean number of topical IOP-lowering medications used was also reduced, from 1.8 at baseline to 0.9 at month 12 and 1.0 at month 18. Increased IOP and dry eye were the most common ocular treatment-emergent adverse events. The mean percentage change in central corneal endothelial cell density from baseline at month 18 (central reading center evaluation) was - 3.47%. In qualitative interviews, most patients (84%, 21/25) reported overall satisfaction with their treatment outcomes.</p><p><strong>Conclusions: </strong>The bimatoprost implant helped control IOP and decrease topical medication use. Throughout the 18 months after implant administration, an estimated 77.7% of eyes required no new added medication for IOP management. Patient-reported outcomes were favorable, and the safety profile of the implant was acceptable.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT04647214, registered 23 November, 2020.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"397-414"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406398","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":"Targeting HER2 in Gastroesophageal Cancer: A New Appetite for an Old Plight.","authors":"Antonella Cammarota, Rachel Woodford, Elizabeth C Smyth","doi":"10.1007/s40265-024-02132-2","DOIUrl":"10.1007/s40265-024-02132-2","url":null,"abstract":"<p><p>The incidence of gastroesophageal cancers is rising, driven, in part, by an increasing burden of risk factors of obesity and gastroesophageal reflux. Despite efforts to address these risk factors, and a growing interest in methods of population screening, the bulk of these tumours are unresectable at diagnosis. In this setting, effective systemic treatments are paramount to improve survival and quality of life. Early and accurate identification of oncogenic drivers, such as human epidermal growth factor receptor 2 (HER2), present in 5-30% of gastroesophageal adenocarcinomas (GEAs), is integral to guide choice of therapies due to the clear predictive implications that arise from overexpression of this receptor. After trastuzumab, the first anti-HER2 agent with approved use in HER2-positive GEA, the addition of pembrolizumab to first-line trastuzumab-chemotherapy and trastuzumab deruxtecan in the refractory space have more recently changed practice. Yet, the response to these agents has been vastly different across patients with HER2-positive disease, underpinning the need for reliable biomarkers of response. Emergent data have suggested that levels of HER2 expression on tissue or liquid biopsies may predict response to first-generation HER2 therapies while HER2 heterogeneity, receptor changes, co-occurring molecular alterations and oncogenic genomic and metabolic reprogramming may be implicated in resistance. A robust knowledge of the mechanisms of resistance and response to HER2-directed therapies is necessary to inform novel strategies of HER2-targeting and guide choice combinations with other biomarker-directed therapies, to improve outcomes from a new generation of clinical trials in HER2-positive GEA. Understanding and close examination of previous failures in this space form an important part of this assessment, as does correlative biomarker and translational work pertaining to the role of HER2 and dynamic changes that result through treatment exposure. In this review, we aim to provide an overview of strategies for HER2 targeting, summarising both the successes and disappointments in this therapeutic landscape and discuss existing challenges and future perspectives on development in this highly morbid tumour type.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"361-383"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022566","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 Expanding Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Armamentarium.","authors":"Dominic P McGovern, Rachel B Jones, David R W Jayne, Rona M Smith","doi":"10.1007/s40265-024-02143-z","DOIUrl":"10.1007/s40265-024-02143-z","url":null,"abstract":"<p><p>The complex pathophysiology of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) is reflected in the heterogeneity of the presenting clinical syndromes caused by these diseases but also provides a variety of conceivable molecular and cellular targets that can be therapeutically manipulated. The last decade has seen an expansion of established and potential therapies for treating AAV, some of which target the dysfunctional autoreactive immune response and others aim to ameliorate the downstream consequences of local vascular inflammation and necrosis. The success and widespread adoption of the anti-CD20 monoclonal antibody, rituximab, as an agent to both induce and maintain remission, has heralded a change in the standard-of-care management of AAV, replacing the \"old guard\" combination of cyclophosphamide and high-dose corticosteroids established in the 1970s. The development and approval of avacopan, a first-in-class small-molecule antagonist to the main receptor for the complement anaphylatoxin C5a, has the potential to reduce the corticosteroid burden experienced by patients with AAV and may also improve outcomes for those with AAV kidney disease. It marks the culmination of almost 20 years of international collaboration, from understanding the pathological role of complement in basic murine models of AAV through to a phase III clinical trial, and emphasises the importance of following promising translational discoveries through to drug development and clinical deployment. This article summarises how recent progress in our understanding of the basic pathophysiology of AAV has resulted in the development of new and effective treatments and, reciprocally, how studying the impact of these treatments in patients has advanced our understanding of dysfunctional immunobiology in disease.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"325-341"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448058","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":"Comment on \"Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review\".","authors":"Rupert Purchase","doi":"10.1007/s40265-024-02141-1","DOIUrl":"10.1007/s40265-024-02141-1","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"443-444"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969843","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":"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":"385-396"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891105/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Liposomal Irinotecan: A Review as First-Line Therapy in Metastatic Pancreatic Adenocarcinoma.","authors":"Michael B Brown, Hannah A Blair","doi":"10.1007/s40265-024-02133-1","DOIUrl":"10.1007/s40265-024-02133-1","url":null,"abstract":"<p><p>Liposomal irinotecan (Onivyde^®), also known as liposomal pegylated irinotecan, has been developed with the intent of maximising anti-tumour efficacy and minimising drug-related toxicities compared with conventional formulations of this topoisomerase 1 inhibitor. In combination with fluorouracil, leucovorin and oxaliplatin (NALIRIFOX), liposomal irinotecan is approved in the USA and the EU for first-line therapy of eligible patients with metastatic pancreatic adenocarcinoma. In a phase III clinical trial, NALIRIFOX significantly improved overall survival (OS) and progression free survival (PFS) compared with gemcitabine plus nanoparticle albumin bound paclitaxel (nab-paclitaxel) as first-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). The safety profile of NALIRIFOX was generally manageable, with diarrhoea, hypokalaemia and neutropenia being the most common grade ≥ 3 treatment-emergent adverse events. Although further analyses will help position the liposomal irinotecan-containing regimen NALIRIFOX in first-line treatment of metastatic pancreatic adenocarcinoma, current evidence indicates that it is a useful addition to treatment options in this patient population.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"255-262"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002231","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":"Efficacy and Safety of CDK4/6 Inhibitors: A Focus on HR+/HER2- Early Breast Cancer.","authors":"Eva Valentina Klocker, Daniel Egle, Rupert Bartsch, Gabriel Rinnerthaler, Michael Gnant","doi":"10.1007/s40265-024-02144-y","DOIUrl":"10.1007/s40265-024-02144-y","url":null,"abstract":"<p><p>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyond progression have been successfully evaluated in the metastatic setting, and are considered a standard of care. Mechanism of action of and resistance mechanisms against CDK4/6i in addition to endocrine resistance represent an important research topic, important for the treatment of HR+ breast cancer. Clinically, CDK4/6i are efficient substances that are usually well tolerated. However, side effects differing between the substances have been reported, and might lead to treatment discontinuation, including in the early disease setting. In the adjuvant setting, the addition of palbociclib to standard endocrine treatment has not improved outcomes, whereas large randomized phase III trials have demonstrated significant disease-free survival benefit for the addition of ribociclib (NATALEE trial) and abemaciclib (monarchE trial). Patient selection, treatment duration, endocrine backbone therapy, and other study details differ between these pivotal trials. This review focuses on both the scientific background as well as all available clinical data of CDK4/6i, with particular emphasis on their use in early breast cancer.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"149-169"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002219","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}