Clinical Drug Investigation最新文献

{"title":"Effectiveness and Safety of Very-Low-Dose Rosuvastatin-Ezetimibe Therapy in Korean Patients with Dyslipidaemia: A Multicentre Prospective Observational Study.","authors":"Ji Woong Roh, Moon-Hwa Park, Ji-Won Son, SungA Bae","doi":"10.1007/s40261-025-01482-3","DOIUrl":"10.1007/s40261-025-01482-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Dyslipidaemia is a key modifiable risk factor for atherosclerotic cardiovascular disease. However, achieving recommended low-density lipoprotein cholesterol (LDL-C) target levels is challenging owing to dose-dependent adverse effects and limited tolerability of high-dose statins. This study evaluated the real-world efficacy and safety of combining very-low-dose rosuvastatin (2.5 mg) with ezetimibe (10 mg) in adult patients with dyslipidaemia across different cardiovascular risk strata.</p><p><strong>Methods: </strong>This multicentre prospective study in South Korea enrolled 2,388 patients. Participants were stratified into low-, moderate-, or high-risk groups on the basis of the 2019 European Society of Cardiology and European Atherosclerosis Society guidelines. Lipid profiles and safety outcomes were assessed at baseline and after 12 weeks. The primary and secondary outcomes were LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) target level achievements, respectively, and adverse events were monitored.</p><p><strong>Results: </strong>After 12 weeks, LDL-C target levels were achieved by 82.6% of low-risk (< 116 mg/dL), 73.9% of moderate-risk (< 100 mg/dL), and 50.4% of high-risk (< 70 mg/dL) patients. Non-HDL-C target level achievement followed a similar trend. Combination therapy with ezetimibe and low-dose statin resulted in significant LDL-C reductions, compared with statins alone. Adverse events were infrequent (0.6%), and only 0.2% of patients discontinued treatment owing to medication-related concerns.</p><p><strong>Conclusions: </strong>Very-low-dose rosuvastatin-ezetimibe combination therapy significantly lowered LDL-C levels and improved lipid profiles across various risk groups, demonstrating a favourable safety profile. These findings support its use as an effective, well-tolerated option for managing dyslipidaemia. Longer-term studies are warranted to evaluate sustained lipid control and cardiovascular outcomes.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"803-813"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069219","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":"Emerging Trends and Future Directions in the Development of Anti-hepatitis B Therapies: A Horizon Scanning Review.","authors":"Kaijie Yao, Hao Feng, Ying Chen, Yun Bao, Mengxia Yan, Wen Li, Bin Wu","doi":"10.1007/s40261-025-01477-0","DOIUrl":"10.1007/s40261-025-01477-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic hepatitis B virus infection remains a Major global public health challenge, affecting over 254 million individuals and causing substantial mortality owing to the limited curative potential of current therapies. This horizon scanning review aims to comprehensively analyze emerging trends and future directions in novel anti-hepatitis B virus therapeutic development, evaluating their progress and potential to achieve functional or complete cures.</p><p><strong>Methods: </strong>We conducted a systematic horizon scanning review from January 2020 to June 2025, searching databases (PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure [CNKI], and WanFang), clinical trial registries (ClinicalTrials.gov, EU Clinical Trials Register, World Health Organization International Clinical Trials Registry, Chinese Clinical Trial Registry, and chinadrugtrials.org), hepatology conference abstracts (American Association for the Study of Liver Diseases, European Association for the Study of the Liver), and pharmaceutical company websites. Inclusion criteria focused on studies detailing novel anti-hepatitis B virus treatments, with data extracted on category, target, clinical phase, and discontinuation reasons.</p><p><strong>Results: </strong>Our analysis identified 161 unique anti-hepatitis B virus treatments: 75 in clinical trials, 34 in preclinical development, and 52 discontinued post-clinical trials because of safety or insufficient efficacy. The pipeline reveals a diversification of targets, with capsid assembly modulators, therapeutic vaccines, and monoclonal antibodies being most prevalent. Three therapies representing novel mechanisms have reached phase III-bepirovirsen (an antisense oligonucleotide), canocapavir (a capsid assembly modulator), and εPA-44 (a therapeutic vaccine), illustrating diversification of late-stage pipelines; however, 6-month off-treatment endpoints should be interpreted cautiously across modalities until durability is established.</p><p><strong>Conclusions: </strong>The robust and diverse pipeline of novel anti-hepatitis B virus treatments offers promise for improving functional cure rates, but definitive conclusions await longer off-treatment follow-up and durability data. Continued research, rational combination strategies, and global collaboration are crucial to overcome challenges and ensure equitable access to these transformative therapies worldwide.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"681-700"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074664","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":"Low-Dose Propranolol versus Amitriptyline for Episodic Migraine Prophylaxis: A Randomized Controlled Trial Assessing Efficacy, Safety, and Cost-Effectiveness.","authors":"Vandana Roy, Nasra Banu, Girish Gulab Meshram, Debashish Chowdhury","doi":"10.1007/s40261-025-01481-4","DOIUrl":"10.1007/s40261-025-01481-4","url":null,"abstract":"<p><strong>Background and objectives: </strong>Direct head-to-head evidence of propranolol and amitriptyline for migraine prophylaxis is limited. This clinical trial compared the efficacy, safety, and cost-effectiveness of low-dose propranolol versus amitriptyline for episodic migraine prophylaxis over a 3-month period.</p><p><strong>Methods: </strong>This randomized, controlled, open-label, prospective, parallel, single-center trial was conducted at a tertiary care hospital in India. A total of 60 prophylaxis-naïve patients with episodic migraine were randomized 1:1 to receive either low-dose propranolol (80 mg/day) or amitriptyline (10 mg/day). The primary outcome was the improvement in the monthly headache frequency at 3 months from baseline, while the secondary outcomes included improvements from baseline in the proportions of patients achieving a ≥ 50% reduction in monthly headache days, headache severity, headache-induced disability, monthly rescue medication intake, quality of life, and cost-effectiveness (measured by the average cost-effectiveness ratio [ACER] and incremental cost-effectiveness ratio [ICER]).</p><p><strong>Results: </strong>At 3 months, propranolol showed a significantly greater reduction in monthly headache frequency compared with amitriptyline (- 3.67 ± 1.47 versus -  2.87 ± 1.36 days, P = 0.03). More patients in the propranolol group (60%) achieved a ≥ 50% reduction in monthly headache days compared with the amitriptyline group (43.33%) (P = 0.02). Propranolol also showed a greater reduction in monthly rescue medication intake (P = 0.01), but differences in headache severity, headache-induced disability, and quality of life were not significant. Both groups experienced mild adverse drug reactions. Cost-effectiveness analysis revealed propranolol had a higher ACER (US $5.44) and ICER (US $0.40/1% reduction) than amitriptyline.</p><p><strong>Conclusions: </strong>In our trial, low-dose propranolol demonstrated superior efficacy to amitriptyline in episodic migraine prophylaxis. Both drugs were well tolerated. Our study suggests that amitriptyline was more cost-effective than propranolol.</p><p><strong>Trial registration number: </strong>Clinical Trial Registry-India (Date: 27 October 2020; registration no.: CTRI/2020/01/022972).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"781-791"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032761","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":"A Retrospective Analysis of the Clinical and Economic Burden of Mitral Regurgitation in Italy Using Real-World Data.","authors":"Paolo Sciattella, Belén Martí-Sánchez, Matteo Vernia, Stefano Giardina, Federico De Marco","doi":"10.1007/s40261-025-01459-2","DOIUrl":"https://doi.org/10.1007/s40261-025-01459-2","url":null,"abstract":"<p><strong>Introduction: </strong>Mitral regurgitation (MR) is the second most common valve disease in Europe with an increasing prevalence, causing a significant healthcare burden and impacting quality of life. Despite its clinical importance, real-world data on MR burden are limited.</p><p><strong>Objectives: </strong>This study aimed to estimate MR prevalence, describe patient profiles, and assess healthcare resource utilization and related costs, stratified by degenerative (DMR) and functional (FMR) aetiologies, using real-world data from Italy.</p><p><strong>Methods: </strong>A retrospective study using Italy's Hospital Discharge Records was conducted including patients discharged in 2018 with a diagnosis of MR. The cohort was stratified into degenerative (DMR) and functional MR (FMR) based on comorbidities and clinical criteria. Patients were followed for 12 months to assess interventions received, including surgical (SMVr) and transcatheter mitral valve repair (TMVr), as well as length of stay, in-hospital mortality, and associated costs.</p><p><strong>Results: </strong>In 2018, 5816 patients who met the eligibility criteria were hospitalised with MR (83.6% DMR, 16.4% FMR). Among DMR patients, 44.2% underwent isolated valve repair (89.7% SMVr, 10.3% TMVr), while 29.1% of FMR patients received repair (59.6% SMVr, 40.4% TMVr). TMVr patients were older (DMR: 41.6%, FMR: 42.9% aged ≥75 years) and had more comorbidities. Untreated patients had higher 1-year in-hospital mortality (DMR: 4.7%, FMR: 8.5%) compared to treated groups and the highest reintervention rate at 1 year (DMR: 19.9%, FMR: 13.3%). Re-intervention rates were lower in DMR (SMVr: 0.4%, TMVr: 0%) versus FMR (SMVr: 0.6%, TMVr: 0.9%). The cost differences between interventions were negligible, primarily reflecting the different DRG tariffs applied for each intervention type.</p><p><strong>Conclusions: </strong>Untreated MR is associated with worse clinical outcomes and higher long-term resource use. These findings support early intervention strategies and highlight the need to improve access to care, especially for high-risk populations. Further studies are warranted to explore outpatient care and address treatment disparities.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184650","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":"CT-P47/Tocilizumab-anoh: A Tocilizumab Biosimilar.","authors":"Aisling McGuigan","doi":"10.1007/s40261-025-01483-2","DOIUrl":"https://doi.org/10.1007/s40261-025-01483-2","url":null,"abstract":"<p><p>CT-P47/tocilizumab-anoh (AVTOZMA^®) is a biosimilar of reference tocilizumab, an IL-6R inhibitor. CT-P47 is approved for treating rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, Coronavirus disease 2019 and cytokine release syndrome in the USA and the EU. CT-P47 has similar physicochemical properties to those of reference tocilizumab, with demonstrated pharmacokinetic comparability in patients with moderate to severe rheumatoid arthritis. In this patient population, CT-P47 demonstrated clinical efficacy equivalent to reference tocilizumab and was generally well tolerated. The overall safety and immunogenicity profiles of CT-P47 were similar to those of reference tocilizumab, and switching from reference tocilizumab to CT-P47 did not affect safety or efficacy. The role of reference tocilizumab in the management of inflammatory diseases is well established and CT-P47 provides an effective biosimilar alternative for patients requiring tocilizumab therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191449","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":"Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Efbemalenograstim Alfa (F-627), a Novel Long-Acting rhG-CSF, in Healthy Chinese Participants: An Open-Label, Single-Center Phase I Study.","authors":"Zhihai Cao, Yao Li, Denny Hou, Shufang Wang, Wei Yao, Gaochong Zhang, Jianmin Chen, Zhengwei Tang, Linda Song, Xingna Zhao, Xiaoxiang Chu, Xiaoyan Wang, Renshu Li, Wei Hu","doi":"10.1007/s40261-025-01488-x","DOIUrl":"https://doi.org/10.1007/s40261-025-01488-x","url":null,"abstract":"<p><strong>Background and objectives: </strong>In clinical practice, granulocyte colony-stimulating factor (G-CSF) is often used to lower infection risk and avoid poor outcomes from chemotherapy dose reduction or delay. Efbemalenograstim alfa (also known as F-627) is a non-pegylated but long-acting (once-per-cycle) recombinant human granulocyte colony-stimulating factor (rhG-CSF) compared with pegfilgrastim. This study was designed to obtain pharmacokinetic (PK)/pharmacodynamic (PD), safety, and tolerability data for F-627 in healthy Chinese participants.</p><p><strong>Methods: </strong>This was a single-center, open-label phase I clinical study involving 24 healthy Chinese volunteers (sex ratio = 1:1). All the participants were administered a single subcutaneous injection of 20 mg F-627 into the abdomen.</p><p><strong>Results: </strong>In this study, 15 (62.5%) participants reported 28 treatment-related adverse events. PK/PD data showed that after a single 20 mg subcutaneous (SC) F-627 abdominal injection in healthy Chinese participants, serum concentrations peaked at 36 h post dose, while the absolute neutrophil count (ANC) peaked at 96 h. After peaking, F-627 serum levels decreased rapidly to low concentrations by 120 h, while ANC declined gradually to near baseline by day 15. Similar trends in serum concentration and ANC kinetics were seen between sex.</p><p><strong>Conclusions: </strong>This phase I study showed that 20 mg F-627 was well tolerated and exhibited a favorable safety profile in a healthy Chinese population. The PK and PD data correlated well and were consistent across sex.</p><p><strong>Trial registration: </strong>This trial was registered at the Chinese Clinical Trial Registry (chictr.org.cn) on 10 September 2024 (registration ID: ChiCTR2400089548).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184668","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":"Resmetirom: The First FDA-Approved Drug for Metabolic Dysfunction-Associated Steatohepatitis (MASH) with a Perspective on Precision Medicine.","authors":"Fengshuo Zhang, Yicong Meng, Bohan Zhao, Ziang Li, Mengran Han, Ming Li, Yun Zhou","doi":"10.1007/s40261-025-01484-1","DOIUrl":"https://doi.org/10.1007/s40261-025-01484-1","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD) involving hepatocyte destruction, inflammation, and typically pericellular fibrosis, potentially progressing to cirrhosis. Resmetirom, a T3 analogue and an oral agonist of thyroid hormone receptor-β(THR-β), represents a significant advancement in targeted drug therapy for MASH as the first US Food and Drug Administration (FDA)-approved treatment. Clinical trials have shown that resmetirom effectively improves MASH markers, reduces liver fat content, and exhibits high selectivity for THR-β, which is predominantly expressed in the liver. Despite promising research data, challenges remain in the treatment of MASH with resmetirom, including adverse reactions and limited efficacy in some patients. This article reviews the discovery, mechanisms, and clinical evaluation of resmetirom in detail, and discusses the challenges encountered in MASH precision therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124546","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":"Mucous Membrane Pemphigoid Outcome Measurement in Clinical Research: A Scoping Review.","authors":"Billal Tedbirt, Eva W H Korte, Marjolein A J Hiel, Joost M Meijer, Maria C Bolling, Phyllis I Spuls, Sjoukje van der Werf, Marc Yale, Barbara Horváth, Pascal Joly","doi":"10.1007/s40261-025-01478-z","DOIUrl":"https://doi.org/10.1007/s40261-025-01478-z","url":null,"abstract":"<p><strong>Background: </strong>Mucous membrane pemphigoid (MMP) is a rare autoimmune bullous disease that predominantly affects mucosae. Treatments for MMP often lack robust evidence and may be poorly tolerated, especially in elderly patients.</p><p><strong>Objective: </strong>This scoping review aims to provide an overview of MMP outcome measurement of the last two decades by mapping and listing all previously reported outcomes and outcome measurement instruments (OMIs).</p><p><strong>Design: </strong>A large scoping review was performed in scientific databases and trial registries (MEDLINE, Embase, CINAHL, PsycINFO, Cochrane CENTRAL, Web of Science, the International Clinical Trials Registry Platform and Clinicaltrials.gov) covering January 2002 to December 2023. Clinical trials, prospective cohort studies, and systematic reviews were included, while retrospective studies were excluded.</p><p><strong>Results: </strong>Thirty-nine studies met the inclusion criteria, including 20 prospective cohort studies, 13 systematic reviews, and 6 clinical trials. A total of 285 outcomes were extracted verbatim and categorized into 29 domains and 9 overarching areas. The most commonly reported outcome areas were related to clinical response, safety, and resource use. The majority were investigator-reported outcomes (85%), with only 8% being patient-reported. Various OMIs (n = 14) were employed, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI) score and tools for assessing ocular impairment and quality of life. Reported outcomes and OMIs are very diverse due to the heterogeneity in the presentation of MMP.</p><p><strong>Conclusions: </strong>The standardized use of consensus-based outcome definitions and high-quality instruments that consider the patient perspective is expected to increase the efficacy of future MMP research and can be achieved by consensus-based selection of outcomes and critical appraisal of the measurement properties of OMIs.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124457","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":"Cost-Estimation Model of Prevented Recurrences with Atezolizumab in Early Non-Small-Cell Lung Cancer in Italy.","authors":"Andrea Marcellusi, Marco Belfiore, Rosaria Tempre, Maria Buonfiglio, Alessandro Russo","doi":"10.1007/s40261-025-01469-0","DOIUrl":"https://doi.org/10.1007/s40261-025-01469-0","url":null,"abstract":"<p><strong>Background: </strong>Patients with early-stage non-small-cell lung cancer (eNSCLC) often experience disease recurrence after surgery and adjuvant chemotherapy, leading to a substantial clinical and economic burden. The introduction of immunotherapy such as atezolizumab in the adjuvant setting may offer both clinical benefits and healthcare cost reductions by preventing disease progression.</p><p><strong>Objectives: </strong>This analysis aimed to estimate the economic impact of prevented recurrences by measuring the costs avoided in the Italian population potentially eligible for adjuvant atezolizumab.</p><p><strong>Methods: </strong>A cost-consequence analysis was developed using a published model, adapted to the Italian context, to estimate the number of recurrences per year from 2023 to 2033, comparing scenarios 'with' and 'without' atezolizumab. Epidemiological and clinical input was obtained from published literature, clinical trials, and local market research. Direct healthcare costs were sourced from an Italian real-world study. The Italian national health system (NHS) perspective was considered, and a deterministic one-way sensitivity analysis was performed to evaluate the uncertainty over the main parameters.</p><p><strong>Results: </strong>Over the period considered, 2582 patients with stage II-IIIA eNSCLC (7th edition of the TNM [tumour, node, metastases] classification) after resection and chemotherapy were estimated annually. Of these, 720 (27.9%) were potentially eligible to receive atezolizumab according to the approved indication. Overall, the model estimated 2556 recurrences for the eligible patients, which generated an economic burden of €11.02 million yearly. The introduction of atezolizumab could avoid 720 recurrences (111 locoregional and 609 metastatic), resulting in a direct healthcare cost reduction of €3.11 million annually from the perspective of the Italian NHS. One-way sensitivity analysis showed moderate base-case changes, especially due to drug costs in the metastatic settings.</p><p><strong>Conclusions: </strong>Recurrences are common among patients with eNSCLC and are associated with a remarkable increase in total direct costs. It appears that adjuvant atezolizumab would prevent a relevant number of events, with potential savings in recurrence-related costs from the perspective of the NHS in Italy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079738","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":"Memantine for the Treatment of Primary Negative Symptoms in Schizophrenia: A Meta-analysis of Randomized Controlled Trials.","authors":"Houlin Hong, Jack Donlon, Martin Schaefer, Susanne Sarkar, Dragana Bugarski-Kirola, Mujeeb U Shad, Wei Hou, Matthias Kirschner, Sajoy P Varghese, Ludmil Mitrev, Valentina Echeverria, John Dibato, Selene R T Veerman, Rohit Aiyer, Thomas N Ferraro, Gerardo Villarreal, Shafiqur Rahman, Trevor W Stone, Maju M Koola","doi":"10.1007/s40261-025-01465-4","DOIUrl":"10.1007/s40261-025-01465-4","url":null,"abstract":"<p><strong>Background: </strong>Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist with favorable safety and side effect profiles. There is a growing body of evidence for memantine as an adjunctive therapy for the positive, negative, and cognitive symptoms of schizophrenia.</p><p><strong>Objective: </strong>This meta-analysis examined the efficacy of memantine as an add-on to treatment with antipsychotic(s) for the primary negative symptoms (PNS) of schizophrenia.</p><p><strong>Methods: </strong>We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and searched for relevant publications in PubMed, Cochrane Library, PsycINFO, Embase, and China Journal Net databases from inception using the following search terms: memantine, schizophrenia, randomized controlled trials (RCTs), RCT, and clinical trial. Searches were limited to English- and Chinese-language articles to date. Standardized mean differences (SMDs) with 95% confidence intervals were calculated using RevMan 5.4 to assess the effect size. Risk of bias was assessed using RoB 2.0.</p><p><strong>Results: </strong>In total, 13 RCTs were identified (N = 681). Memantine was superior to placebo in treating negative symptoms, with an SMD of 0.79 (p = 0.0001, N = 631, 12 RCTs). Analysis of three studies whose corresponding authors provided original datasets showed an SMD of 2.16 (p = 0.25, N = 97) after adjusting for change in psychosis, depression, and extrapyramidal symptoms, suggesting that memantine is efficacious in treating PNS. Additionally, cognitive testing significantly improved, with an SMD of 0.66 (p = 0.0001, N = 395, eight RCTs). Positive symptoms were not significantly improved (SMD = 0.24, p = 0.1, N = 631, 12 RCTs).</p><p><strong>Conclusions: </strong>To our knowledge, this is the first study showing a large effect size for treating PNS with memantine. Although statistical significance was not reached because of the small sample size (N = 97), the results were as expected because drugs such as memantine that act at NMDA receptors are unlikely to be effective as stand-alone treatments. Future RCTs should evaluate NMDAergic drugs in combination with complementary medications to optimize therapeutic effects for all three domains of schizophrenia psychopathology.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"627-642"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759333","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}