Clinical Drug Investigation最新文献

{"title":"Correction: Mitomycin Intravesical Solution: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40261-025-01491-2","DOIUrl":"https://doi.org/10.1007/s40261-025-01491-2","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249904","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":"Efbemalenograstim Alfa, an Fc Fusion Protein, Long‑Acting Granulocyte Colony-Stimulating Factor for Reducing the Risk of Chemotherapy-Induced Neutropenia: Results of a Phase II Randomized, Multicenter, Open‑Label Trial.","authors":"Dongmei Ji, Shufang Wang, Wei Yao, Denny Hou, Xiaoyan Wang, Changsheng Ye, Hongsheng Li, Hongjian Yang, Jilin Yi, Jinsong Lu, Haibo Wang, Xiaohong Xu, Dongyan Cai, Xiaoan Liu, Xi Yan, Jianyun Nie, Shude Cui, Hongchuan Jiang, Junning Cao","doi":"10.1007/s40261-025-01479-y","DOIUrl":"https://doi.org/10.1007/s40261-025-01479-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neutropenia is the most severe hematologic toxicity of myelosuppressive chemotherapy. The objective of this study was to evaluate the safety and efficacy of efbemalenograstim alfa versus filgrastim for neutropenia support in patients with breast cancer receiving myelosuppressive chemotherapy and find the recommended dose for phase III clinical trials.</p><p><strong>Methods: </strong>This was an open-label, dose-finding, active-controlled, phase II study. In total, 138 patients with postoperative breast cancer received up to four cycles of epirubicin 100 mg/m² + cyclophosphamide 600 mg/m² (EC) chemotherapy. Patients were randomized in a 1:1:1 ratio to efbemalenograstim alfa (10 mg/dose or 20 mg/dose) or filgrastim group. Duration and incidence rate of moderate or severe neutropenia, depth of absolute neutrophil count (ANC) nadir, time to ANC recovery post nadir, and safety information were evaluated.</p><p><strong>Results: </strong>The mean duration of moderate and severe neutropenia in cycle 1 was 0.8, 0.6, and 0.8 days for the 10 mg/dose efbemalenograstim alfa, 20 mg/dose efbemalenograstim alfa, and filgrastim groups, respectively. The incidence rate of moderate and severe neutropenia in cycle 1 was lower in 20 mg/dose efbemalenograstim alfa (25.5%) than that in 10 mg/dose efbemalenograstim alfa (35.1%) and filgrastim (38.5%), and no significant differences were observed for the two doses of efbemalenograstim alfa with filgrastim (p = 0.815; p = 0.246, respectively). The ANC nadir occurred between days 9 and 10 in cycle 1, and the median ANC nadir in the 20 mg/dose efbemalenograstim alfa group was higher than that in the 10 mg/dose efbemalenograstim alfa and filgrastim groups (2.2 × 10⁹/L versus 1.7 × 10⁹/L and 1.4 × 10⁹/L, respectively). The time to ANC recovery post nadir in the 20 mg/dose efbemalenograstim alfa group was shorter, but no significant differences were observed for the two doses of efbemalenograstim alfa with filgrastim (0.8 and 1.7 versus 1.2 days, respectively). Efbemalenograstim alfa exhibited similar safety profile to filgrastim. No febrile neutropenia occurred. The incidence rates of common adverse reactions related to the study drugs, such as back pain and bone pain, were lower in the efbemalenograstim alfa groups than that in the filgrastim group (10.3% and 8.0% versus 24.4%).</p><p><strong>Conclusions: </strong>The efficacy and safety of efbemalenograstim alfa are comparable to those of filgrastim in treating chemotherapy-induced neutropenia in patients with breast cancer receiving EC chemotherapy. Efbemalenograstim alfa at a dose of 20 mg is the recommended dose for phase III clinical trials.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT02521441, on 13 August 2015.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250073","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":"Disproportionality Analysis of Pulmonary Adverse Events Associated with Trastuzumab Deruxtecan Using the Japanese Adverse Drug Event Report Database.","authors":"Yuko Kanbayashi, Risa Morioka, Keiko Hosohata","doi":"10.1007/s40261-025-01490-3","DOIUrl":"https://doi.org/10.1007/s40261-025-01490-3","url":null,"abstract":"<p><strong>Aim: </strong>This study was conducted to examine disproportionality, times to onset, incidence rates, and outcomes of trastuzumab deruxtecan-associated pulmonary adverse events (AEs) using the Japanese Adverse Drug Event Report database.</p><p><strong>Methods: </strong>We analyzed data for the period from April 2004 to December 2024. Data on pulmonary AEs were extracted, and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs).</p><p><strong>Results: </strong>Of the 3,221,393 reports analyzed, we identified 1561 reports of AEs associated with trastuzumab deruxtecan, including 505 pulmonary AEs. Only 474 reports were identified as signal-positive: interstitial lung disease, pulmonary toxicity, pneumonitis, and Pneumocystis jirovecii pneumonia. Among these, interstitial lung disease was the most frequently reported (26.6%) and included several fatal cases. Histograms of median times to onset for the four detected pulmonary AE signals showed that AEs occurred at a median of 7-27.5 days after trastuzumab deruxtecan administration. Weibull distributions showed that interstitial lung disease occurred early after administration (early failure type), but pulmonary toxicity occurred constantly throughout the exposure period (random failure type).</p><p><strong>Conclusions: </strong>We focused on pulmonary AEs associated with trastuzumab deruxtecan as postmarketing AEs. Serious outcomes can arise after trastuzumab deruxtecan administration. Patients should be monitored for signs of onset of these AEs not only at the start of administration but also over an extended period.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145250096","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":"Budget Impact and Financial Analysis of Outpatient Dalbavancin in an Urban, Non-Teaching, Community Hospital.","authors":"Karan Raja, Brandon Chen, Onrina Chandra, Mitesh Patel, Mona Philips","doi":"10.1007/s40261-025-01486-z","DOIUrl":"https://doi.org/10.1007/s40261-025-01486-z","url":null,"abstract":"<p><strong>Background: </strong>Acute bacterial skin and skin structure infections (ABSSSI), diabetic foot infections (DFI), and osteomyelitis often require extended antimicrobial therapy courses. Dalbavancin's long half-life allows outpatient or emergency department (ED) management of patients not amenable to oral antimicrobials and/or outpatient infusion.</p><p><strong>Objective: </strong>To provide a budget-impact analysis and real-world assessment of dalbavancin cost and reimbursement data, and model drug acquisition cost-avoidance compared to daptomycin and oral linezolid in outpatient and ED patients at our institution (New Jersey, USA).</p><p><strong>Methods: </strong>All patients treated with dalbavancin in the ED or outpatient wound clinic during the one-year study period with available drug-specific reimbursement data were included. Wholesale acquisition costs were compared between dalbavancin, daptomycin, and oral linezolid. We conducted a regression analysis studying profit changes with patient weight, indication, drug-specific reimbursement, and treatment duration. We fitted a linear mixed-effects model and paired t-test to explore relationships between potential profit and various predictors while accounting for random effects of different indications. Paired t-tests were conducted evaluating potential profit and cost avoidance from the hospital and institutional pharmacy perspective associated with dalbavancin across treatment durations and indications.</p><p><strong>Results: </strong>Eighty-eight individual patient encounters were included in the final analysis. Treatment indications included ABSSSI (48.9%), DFI (33%), diabetic foot osteomyelitis (9%), osteomyelitis (6.8%), and septic arthritis (2.3%). An overall positive reimbursement of approximately US$3500 per patient per encounter was realized. Drug acquisition cost modeling demonstrated variable cost avoidance with dalbavancin compared to daptomycin or oral linezolid based on anticipated treatment duration. Average wholesale acquisition cost difference ranged from a potential loss of US$427.64 to a gain of US$12,557.94 and a loss of US$829.28 to possible gain of US$4370.32 compared to daptomycin and linezolid, respectively, based on treatment duration.</p><p><strong>Conclusions: </strong>Outpatient dalbavancin utilization presents an opportunity to realize net positive reimbursement and minimize pharmacy drug acquisition costs. Our study suggests that dalbavancin utilization presents significant cost advantages over intravenous daptomycin in both short and long treatment durations and over oral linezolid in long durations.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249956","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":"Intra-arterial Injection of OTR4132, a Novel Neuroprotector in Acute Ischemic Stroke: The MaTRISS Trial.","authors":"Xavier Barreau, René Anxionnat, Olivier Heck, Igor Sibon, Charlotte Rosso, Catherine Oppenheim, Francisco Moniche, Frédéric Sedel, Franck Chiappini, Agnès Choppin, Martin Inizan, Denis Barritault, Olivier Detante","doi":"10.1007/s40261-025-01487-y","DOIUrl":"https://doi.org/10.1007/s40261-025-01487-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>There is an important need for the development of neuroprotective therapeutic agents that could be combined to reperfusion strategies in acute ischemic stroke to improve patient prognosis. OTR4132 is a polymer of glucose engineered to mimic heparan sulfates (HS), which demonstrated neuroprotective effects in animal models. The aim of this study was to assess the safety of OTR4132 and to identify the highest, and well-tolerated, single dose of OTR4132 in patients with anterior circulation acute ischemic stroke who underwent endovascular thrombectomy (EVT).</p><p><strong>Methods: </strong>The MaTRISS study is a multi-center, first-in-man, open-label, dose-escalation study. OTR4132 was administered intra-arterially immediately after EVT recanalization. Dose levels were determined on the basis of preclinical studies. Six doses (from 0.2 to 2.5 mg) were planned to be administered in groups of at least three patients. Each dose escalation was authorized by the data safety monitoring board (DSMB) after reviewing all clinical, biological, and radiological data from a dose group up to 7 days post-administration. Key inclusion criteria were an acute ischemic stroke in the anterior circulation territory and endovascular thrombectomy performed with recanalization (thrombolysis in cerebral infarction [TICI] score of 2b-3) confirmed by angiography. The primary endpoint was the rate of investigational treatment-related severe adverse events occurring from baseline to 7 days after injection. All other safety and efficacy endpoints were exploratory and included all serious and non-serious adverse events, stroke lesion volumes, National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), Modified Barthel Index (BI), and Montreal Cognitive Assessment (MoCA) from baseline up to 3 months.</p><p><strong>Results: </strong>In total, 19 patients were recruited from three centers in France between March 2022 and March 2024 and six different doses of OTR4132 were tested (in n patients): 0.2 mg (3), 0.5 mg (3), 1 mg (3), 1.5 mg (6), 2 mg (3), and 2.5 mg (1). No adverse drug events and no changes in vital signs or laboratory parameters were observed up to 3 months following administration, regardless of administered doses. Four patients presented at least one serious adverse event. None was considered linked to the investigational treatment on the basis of investigator and DSMB assessment. One patient died of intracranial hemorrhagic transformation at 24 h and the causality link between OTR4132 administration and death remained unknown.</p><p><strong>Conclusions: </strong>The highest tolerated dose of OTR4132 was the highest dose administered (i.e., 2.5 mg). These safety results need to be confirmed in a larger multicenter randomized placebo-controlled clinical trial. The trial was first registered in clinicaltrials.gov on 5 September 2019 (NCT04083001).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205744","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":"Revisiting the Role of Serotonin in Attention-Deficit Hyperactivity Disorder: New Insights from Preclinical and Clinical Studies.","authors":"Matia B Solomon, Brittney Yegla, Jeffrey H Newcorn, Vladimir Maletic, Jonathan Rubin, Trevor W Robbins","doi":"10.1007/s40261-025-01473-4","DOIUrl":"10.1007/s40261-025-01473-4","url":null,"abstract":"<p><p>Attention-deficit hyperactivity disorder (ADHD) is characterized by core symptoms of inattention, hyperactivity, and impulsivity. Aberrant dopaminergic and noradrenergic neurotransmission are often implicated in the pathogenesis of these symptoms because ADHD treatments increase synaptic levels of these neurotransmitters in brain regions associated with attention and impulse control. However, some ADHD treatments also enhance serotonergic neurotransmission in these regions, which could contribute to their efficacy. Here, we review preclinical and clinical data highlighting functional interactions between the serotonergic and catecholaminergic systems in mediating ADHD phenotypes and responses to treatment. The potential utility of serotonergic compounds for treating distinct behavioral features and psychiatric comorbidities (e.g., depression) is also discussed. Overall, preclinical and clinical studies underscore important neuromodulatory effects of serotonin on the catecholaminergic system in mediating distinct ADHD behavioral phenotypes, notably hyperactivity-impulsivity and emotional dysregulation. Incorporating a basic understanding of dynamic monoaminergic interactions and their contributions to ADHD symptoms may identify new targets for treatment. Beyond ADHD core symptoms, emotional dysregulation, which is closely linked to serotonergic dysfunction, is common in ADHD and significantly contributes to negative outcomes across the lifespan. Therefore, an expanded conceptualization of ADHD that includes emotional dysregulation may facilitate insight into ADHD pathology and treatment.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"701-742"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond Antihistamines: How Biologic and Small-Molecule Therapies Are Transforming Chronic Spontaneous Urticaria Care in Adults.","authors":"Adeeb A Bulkhi","doi":"10.1007/s40261-025-01480-5","DOIUrl":"10.1007/s40261-025-01480-5","url":null,"abstract":"<p><p>Chronic urticaria (CU) is a complex, disabling skin disease characterized by recurrent, pruritic wheals and frequently angioedema lasting for 6 weeks or more. Although non-sedating H1-antihistamines remain the first-line therapy, a significant subset of patients (50%) remains symptomatic despite antihistamines, underscoring an unmet need for more targeted treatments. Recent advances in our understanding of CU pathophysiology have led to the development of biologic agents-most notably omalizumab and dupilumab-as well as an expanding pipeline of small-molecule therapies targeting key intracellular signaling pathways (e.g., Bruton's tyrosine kinase [BTK] and Janus kinase [JAK] inhibitors). Therapeutic targets for biologics in chronic spontaneous urticaria (CSU) include IgE, IL-4/IL-13, and IL-5 pathways. This review provides a comprehensive overview of the underlying immunopathogenesis of CSU in adults, critically examines the limitations of conventional therapy (primarily second-generation H1-antihistamines), and reviews the current status and future prospects of biologic and small-molecule treatments. It synthesizes the rapidly evolving landscape of these therapies focusing on therapeutic mechanisms of biologic and small-molecule therapies, recent clinical trial data, and potential for personalized treatment, building on and extending prior reviews. We also discuss practical considerations-including endotyping, cost-effectiveness, and long-term safety, and outline future research directions toward personalized management of chronic urticaria.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"743-766"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145079666","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":"The Effect of Multiple Oral Doses of a Glycine Transporter 1 Inhibitor, Iclepertin (BI 425809), on the Steady-state Pharmacokinetics of a Combined Oral Contraceptive Containing Ethinylestradiol and Levonorgestrel: a Phase I Clinical Trial in Healthy Females.","authors":"Shilpa Madari, Yesilda Balavarca, Yury Shatillo, Corey Reuteman-Fowler, Michael Desch","doi":"10.1007/s40261-025-01472-5","DOIUrl":"10.1007/s40261-025-01472-5","url":null,"abstract":"<p><strong>Background: </strong>Iclepertin is a selective inhibitor of glycine transporter 1 recently investigated as a novel treatment for cognitive impairment associated with schizophrenia. Iclepertin is a potential mild inducer of liver cytochrome P450 3A4, which metabolises ethinylestradiol and levonorgestrel, which are used in combined oral contraceptives (OCs).</p><p><strong>Objectives: </strong>This trial investigated the potential drug interaction effect of steady-state iclepertin on the steady-state pharmacokinetics of combined OCs.</p><p><strong>Methods: </strong>This phase I, non-randomised, open-label, two-period, fixed-sequence trial was conducted in healthy pre-menopausal female volunteers aged 18-35 years. In period 1, participants received a combined OC (ethinylestradiol 30 µg/levonorgestrel 150 µg once daily; reference treatment). In period 2, participants received a combined OC and iclepertin 10 mg once daily (test treatment). Primary pharmacokinetic endpoints of ethinylestradiol or levonorgestrel in plasma at steady state over a uniform dosing interval τ were area under the concentration-time curve (AUC_τ,ss) and maximum and minimum measured concentration (C_max,ss and C_min,ss); drug interaction potential was estimated by geometric mean ratios (test treatment/reference treatment) with two-sided 90% confidence intervals (CIs) using analysis of variance. Safety assessments included monitoring adverse events (AEs).</p><p><strong>Results: </strong>In total, 19 participants entered the trial; 17 were treated (periods 1 and 2). Steady-state pharmacokinetics of ethinylestradiol and levonorgestrel were similar with and without iclepertin; geometric mean ratios for AUC_τ,ss, C_max,ss, and C_min,ss were slightly above 100%, and 90% CIs were within standard bioequivalence boundaries (80-125%). The number of on-treatment AEs was similar in period 1 (n = 13) and period 2 (n = 15); AEs were of mild-to-moderate severity.</p><p><strong>Conclusion: </strong>Iclepertin 10 mg had no meaningful effect on the pharmacokinetics of ethinylestradiol and levonorgestrel, suggesting that these drugs can be administered concomitantly.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT05613777; registered on 18 October 2023).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"767-779"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991673","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":"Off-Label Prescription of Benzodiazepines: A Retrospective Cohort Study of Prescribing Prevalence in Primary Care.","authors":"Kevin Trimm, Maria-Teresa Moraga, Bärbel Knäuper, Elham Rahme, Emily Gibson McDonald, Robyn Tamblyn","doi":"10.1007/s40261-025-01476-1","DOIUrl":"10.1007/s40261-025-01476-1","url":null,"abstract":"<p><strong>Background and objectives: </strong>Benzodiazepines are commonly prescribed medications approved for and used in the treatment of anxiolytic and sleep disorders, as well as for seizures, and alcohol withdrawal. However, benzodiazepines are also controlled substances because of their potential for abuse and personal harm, which are especially prevalent among older people. It is therefore important to understand how benzodiazepines are being prescribed, and the prevalence of off-label benzodiazepine prescribing, of which very little is known because of challenges in documenting treatment indication. The aim of this study was to detail the prevalence of benzodiazepine off-label prescribing.</p><p><strong>Methods: </strong>Data from the MOXXI (Medical Office of the XXIst century) electronic health record system in Quebec Canada were used, where specifying the treatment indication for each prescription is required, to estimate the prevalence of off-label prescribing and indications for off-label use of benzodiazepines. Each drug indication was retrospectively classified as either on-label or off-label according to the Health Canada drug database. Off-label prescriptions were further classified as having class congruence supporting their prescription if another benzodiazepine had been approved for the indication by Health Canada.</p><p><strong>Results: </strong>There were 20,125 (17.0%) adult patients prescribed benzodiazepines out of the 118,223 patients enrolled in the MOXXI system. The patients were predominantly female (65.6%) and tended to be older with an average age of 60.14 years at the time of the first benzodiazepine prescription. A total of 101,583 unique prescriptions were written for 14 different benzodiazepines. An approximately equal number of benzodiazepines were prescribed on- and off-label (49.3% on-label, 49.2% off-label). Most off-label prescription indications were classified as having class congruence (95.2%).</p><p><strong>Conclusions: </strong>Benzodiazepines were frequently prescribed in the province of Quebec and were prescribed off-label approximately half of the time. When prescribed off-label, we found that most of these prescriptions were for indications that were approved for other benzodiazepines. The most common indication for off-label benzodiazepine prescriptions with class congruence was insomnia.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"793-801"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999851","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":"Radioligand Therapies (RLTs) and Healthcare System Readiness: From the Experience in GEP-NET, a Retrospective Analysis on DRG and Mobility to Improve the Accessibility to the Future RLT in Italy.","authors":"Paolo Sciattella, Matteo Scortichini, Orazio Caffo, Marco Maccauro, Alfredo Muni, Francesco Panzuto","doi":"10.1007/s40261-025-01471-6","DOIUrl":"10.1007/s40261-025-01471-6","url":null,"abstract":"<p><strong>Background and objectives: </strong>Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare diverse group of malignancies, which range from well-differentiated indolent tumors to high-grade aggressive forms. Based on the World Health Organization classification, GEP-NETs are divided into well-differentiated neuroendocrine tumors and poorly differentiated carcinomas. While localized GEP-NETs are primarily treated surgically, non-resectable GEP-NETs have evolved toward targeted therapies, including radioligand therapy. This study describes inpatient resource utilization and inter-regional healthcare mobility for patients with GEP-NETs in Italy, focusing on radioligand therapy.</p><p><strong>Methods: </strong>We retrieved Italian Hospital Discharge Records (SDO) from 2018 to 2021. Given the absence of specific International Classification of Diseases, Ninth Revision, Clinical Modification codes for GEP-NETs, all potentially related diagnoses were included. Radioligand therapy-related hospitalizations were identified using Diagnosis-Related Group code 409 for radiotherapy, focusing on discharge disciplines of nuclear medicine, radiotherapy, or radiation oncology. We analyzed hospitalization rates by region and regimen and assessed inter-regional mobility using the Attraction and Escape Mobility Indexes.</p><p><strong>Results: </strong>Over the study period, 4837 radioligand therapy-related GEP-NET hospitalizations were recorded, with 2942 involving the targeted disciplines. Hospitalizations increased by 48.4%, mainly owing to growth in short-stay (0-1 day) discharges (from 37 in 2018 to 228 in 2021), while longer stays (≥ 2 days) rose from 552 to 644. Day hospital accounted for only 0.2% of cases. Regional disparities were prominent, with Emilia-Romagna, Lombardia, and Sicilia managing 88.9% of cases; ten regions recorded no hospitalizations, reflecting a high mobility index (45.8%) and significant inter-regional patient mobility.</p><p><strong>Conclusions: </strong>The study underscores the need for regulatory adjustments, resource allocation improvements, and healthcare system adaptations to effectively support innovative therapies for GEP-NETs. Addressing these needs is essential to optimize patient outcomes and address regional disparities in Italy's healthcare system.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"815-824"},"PeriodicalIF":2.7,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476415/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}