Clinical Drug Investigation最新文献

{"title":"Effectiveness and Tolerability of Vortioxetine in Major Depressive Disorder: A Real-World Study in Switzerland.","authors":"Martin Kammerer, Gregor Hasler, Barbara Hochstrasser, Axel Baumann, Alexandra Sousek","doi":"10.1007/s40261-026-01537-z","DOIUrl":"10.1007/s40261-026-01537-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>Vortioxetine is widely used in Switzerland for treating major depressive episodes, but systematically collected data from routine clinical practice are not available. We evaluated real-world effectiveness and tolerability of vortioxetine for treating major depressive episodes in Swiss clinical practice.</p><p><strong>Methods: </strong>A prospective non-interventional observational study was conducted with an observation period of approximately 8 weeks from vortioxetine initiation. Adults with a current major depressive episode for whom a decision to initiate vortioxetine had been made independent of the study were eligible for inclusion. Assessment of depressive symptoms, functioning, safety and tolerability were performed at four study visits. Pre-planned explorative descriptive statistics were applied.</p><p><strong>Results: </strong>Of 226 patients enrolled, 208 (92.0%) completed the study. At baseline, the mean (standard deviation) sum of the unanchored Montgomery-Åsberg Depression Rating Scale items was 34.3 (8.89), indicating severe depression. Depression severity tended to be underestimated when relying on clinical estimation without any scale alone. Significant reductions were observed from baseline to visit 4 in the sum of the unanchored Montgomery-Åsberg Depression Rating Scale items, in all individual items, and in the Clinical Global Impression-Severity scale (all p < 0.001). The severity of impairment of all assessed functioning domains also decreased. Adverse drug reactions were reported in 7.5% of patients. Effectiveness and tolerability of vortioxetine was rated good or very good by >88% of clinicians and patients.</p><p><strong>Conclusions: </strong>Patients who initiated vortioxetine for treating a major depressive episode experienced improvements in depressive symptoms and functioning. Vortioxetine was well tolerated. Underestimation of depressive episode severity by clinicians reinforces the importance of using rating scales in clinical practice.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"501-516"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147462788","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":"Clinical Trial Comparison of Dupilumab and Nemolizumab for Prurigo Nodularis FDA-Approved Biologic Therapy Selection in Prurigo Nodularis.","authors":"Anna Robertson, Craig Rohan","doi":"10.1007/s40261-026-01545-z","DOIUrl":"10.1007/s40261-026-01545-z","url":null,"abstract":"<p><p>Prurigo nodularis (PN) is a chronic, pruritic skin disorder characterized by significant morbidity and historically limited treatment options. The recent approval of biologic therapies has rapidly changed the treatment landscape, with dupilumab and nemolizumab now Food and Drug Administration (FDA)-approved for PN. This article provides a clinically relevant overview of completed randomized trials, highlighting differences in efficacy, timing of response, and symptom targets. Data were extracted from six compound randomized clinical trials (two dupilumab trials and four nemolizumab trials) identified on ClinicalTrials.gov through January 2025. Across phase 3 studies, dupilumab demonstrated sustained reductions in itch severity and lesional disease, with approximately 58-60% of patients achieving a ≥ 4-point improvement in Worst Itch Numeric Rating Scale (WI-NRS) scores and 45-48% achieving Investigator Global Assessment for Prurigo Nodularis-Stage (IGA PN-S) success by week 24. Nemolizumab showed a more rapid onset of antipruritic effect, with 41-56% of patients achieving a ≥ 4-point improvement in Peak Pruritus Numeric Rating Scale (PP-NRS) scores as early as week 4, along with clinically meaningful improvements in sleep disturbance by week 16. Both therapies demonstrated manageable safety profiles, with predominantly mild to moderate adverse events and low rates of serious adverse events, although nemolizumab was associated with higher overall rates of mild to moderate adverse events. These findings suggest that dupilumab may offer greater lesional clearance at later time points, whereas nemolizumab may provide faster itch relief and less sleep disturbance. These findings support a phenotype-guided approach to biologic selection while highlighting the need for further comparative studies.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"479-487"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572218","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":"Pharmacokinetic Drug-Drug Interaction of Leritrelvir in Healthy Chinese Volunteers: A Single-Arm, Open-Label, Dual-Cohort Study.","authors":"Jiao Peng, Juan Chen, Xiao-Xiao Du, Hai-Jun Li, Ru-Zhai Qin, Si-Han Chen, Xian Liu, Qi Cheng, Xiao-Mei Li, Dong-Xiang Huang, Lian Duan, Ming-Yan Li, Wen-Zheng Wu, Li-Ka Ye, You-Yun Li, Zhi-Hong Xie, Ke Han","doi":"10.1007/s40261-026-01556-w","DOIUrl":"https://doi.org/10.1007/s40261-026-01556-w","url":null,"abstract":"<p><strong>Background and objectives: </strong>Preclinical studies have shown that leritrelvir, an anti-coronavirus disease 2019 (COVID-19) drug, is a substrate of CYP3A and P-gp. It also inhibits CYP3A, CYP2C19, and OATP1B3. This study systematically evaluated leritrelvir's pharmacokinetic interactions with sensitive substrates, inhibitors, or inducers of the aforementioned metabolic pathways. The short-term safety of co-administration was also assessed.</p><p><strong>Methods: </strong>We conducted a phase Ⅰ, single-arm, open-label, dual-cohort clinical trial in healthy Chinese adults. Cohort 1 evaluated the effect of multiple doses of leritrelvir on the pharmacokinetics of midazolam, omeprazole, and rosuvastatin. Serial blood samples were collected for the determination of midazolam and omeprazole concentrations at pre-dose and post-dose on days 1-2 (midazolam and omeprazole alone) and days 10-11 (midazolam and omeprazole co-administered with leritrelvir). For rosuvastatin, blood samples were collected at pre-dose and post-dose on days 3-6 (rosuvastatin alone) and days 12-15 (rosuvastatin co-administered with leritrelvir). Cohort 2 assessed the effect of multiple dose administration of verapamil and rifampicin on the pharmacokinetics of leritrelvir. Serial blood samples were collected for the determination of leritrelvir concentrations at pre-dose and post-dose on days 1-4 (leritrelvir alone), days 9-12(leritrelvir co-administered with verapamil), and days 28-31(leritrelvir co-administered with rifampicin).</p><p><strong>Results: </strong>In cohort 1, leritrelvir minimally affected omeprazole and rosuvastatin exposure. The geometric mean ratios (GMRs) for their area under the plasma concentration-time curve from time zero to the lowest detectable plasma concentration (AUC_0-t) were 98.3% and 113.2%, respectively, versus administration alone. In contrast, leritrelvir increased midazolam AUC_0-t to 232.1% (GMR) versus administration alone. In cohort 2, verapamil increased leritrelvir AUC_0-t to 251.8% (GMR) versus administration alone. Rifampicin decreased leritrelvir AUC_0-t to 80.6% (GMR).</p><p><strong>Conclusions: </strong>The potential for drug-drug interactions between leritrelvir and CYP2C19 or OATP1B3 is low. The same applies to its interaction with a CYP3A inducer. However, as a moderate CYP3A inhibitor, leritrelvir requires caution when co-administered with CYP3A substrates, especially those with a narrow therapeutic index. Although moderate inhibitors of CYP3A and P-gp increased the leritrelvir exposure, this increase may not require dose adjustment on the basis of the phase I PK data of leritrelvir.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT06031454.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811778","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":"Correction: A Single-Center, Randomized, Open-Label, Two-Formulation, Two-Sequence, Two-Period Crossover Study to Evaluate the Bioequivalence of Two Eltrombopag Olamine Tablets (25 mg) in Healthy Chinese Subjects in the Fed State.","authors":"Keyi Wu, Qing Ren, Yanli Wang, Yannan Zhou, Zhengzhi Liu, Yang Cheng, Qiaohuan Deng, Yingzi Cui, Haimiao Yang","doi":"10.1007/s40261-026-01542-2","DOIUrl":"https://doi.org/10.1007/s40261-026-01542-2","url":null,"abstract":"","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764588","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":"Clinical Benefit of Multiple Myeloma Drugs at Regulatory Approval in Brazil, Europe, and the USA: A Retrospective Cohort Study (2003-2024).","authors":"Marina Alacoque Rodrigues, Cristiane Aparecida Menezes de Pádua, Paula Lana de Miranda Drummond, Pedro Henrique Carvalho de Souza, Jéssica Soares Malta, Adriano Max Moreira Reis","doi":"10.1007/s40261-026-01552-0","DOIUrl":"https://doi.org/10.1007/s40261-026-01552-0","url":null,"abstract":"<p><strong>Background and objectives: </strong>The value of new therapies depends on the magnitude of their clinical benefit. In multiple myeloma (MM), numerous drugs have been approved in the past two decades, yet the extent of clinical benefit at authorization remains uncertain. This study evaluated MM drugs approved by the European Medicines Agency (EMA), the Food and Drug Administration (FDA), and the Brazilian Health Regulatory Agency (Anvisa).</p><p><strong>Methods: </strong>This retrospective cohort study assessed MM drugs approved between 2003 and 2024. Data were extracted from publicly available regulatory documents. Clinical benefits were assessed using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale for Haematological Malignancies (ESMO-MCBS:H v 1.1) based on pivotal trials. Descriptive statistics, Kaplan-Meier curves and log-rank tests were performed.</p><p><strong>Results: </strong>During the study period, the EMA approved 17 drugs for MM, with 11 (64.7%) supported by single-arm studies and 4 (23.5%) through accelerated assessment. The FDA also approved 17 drugs, with 12 (70.6%) based on single-arm studies, 11 (64.7%) through expedited pathways, and 8 (47.1%) designated as Breakthrough Therapies. Anvisa approved 12 drugs, with 7 (58.3%) under priority registration. According to the ESMO-MCBS:H v1.1 scoring, only 4 of 17 drugs (23.5%) demonstrated meaningful clinical benefit, defined as a grade ≥4 in the non-curative setting. Accelerated timelines in Brazil were significantly associated with biologicals, monoclonal antibodies, and Breakthrough Therapy status (all p < .05).</p><p><strong>Conclusion: </strong>Most MM therapies approved entered the market with limited evidence of meaningful clinical benefit. These findings support using the ESMO-MCBS:H to guide regulatory and reimbursement decisions in resource-constrained settings.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764579","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":"Efficacy and Safety of Topical Anticholinergics in the Treatment of Primary Axillary Hyperhidrosis: A Systematic Review and Meta-analysis.","authors":"Jiah Kim, Nayoung Han, Hyunji Koo, Younghwa Kim, Eun Jung Hwang, Min-Soo Kim, Christine E Staatz, In-Hwan Baek","doi":"10.1007/s40261-026-01550-2","DOIUrl":"https://doi.org/10.1007/s40261-026-01550-2","url":null,"abstract":"<p><strong>Background: </strong>Topical anticholinergic agents are non-invasive treatment options for primary axillary hyperhidrosis (PAH). Sofpironium bromide was recently approved by the US Food and Drug Administration (FDA). A comprehensive evaluation of the efficacy and safety of available topical anticholinergics may inform clinical practice.</p><p><strong>Objectives: </strong>To assess the efficacy and safety of topical anticholinergic therapies for PAH through systematic review and meta-analysis of randomized controlled trials (RCTs).</p><p><strong>Methods: </strong>Five databases were searched on September 9, 2024. Primary outcomes included a ≥2-point improvement in the Hyperhidrosis Disease Severity Scale (HDSS) and ≥50% reduction in gravimetric sweat production (GSP). Secondary outcomes included subjective symptom improvement and objective sweat reduction. Safety outcomes included treatment-emergent adverse events (TEAEs), anticholinergic-related adverse events, and local application site reactions. The review protocol was registered in PROSPERO (CRD42024583376).</p><p><strong>Results: </strong>Eight RCTs (n = 1921) that evaluated glycopyrronium, sofpironium bromide, and umeclidinium were included. Topical agents significantly outperformed placebos for HDSS ≥2-point improvement (risk ratio [RR]: 2.40; 95% confidence interval [CI]: 2.01-2.86) and GSP ≥50% reduction (RR: 1.43; 95% CI: 1.21-1.70). Sofpironium was the most effective HDSS treatment, whereas glycopyrronium showed highest efficacy against GSP. Topical agents were associated with increased risk of TEAEs (RR: 1.43; 95% CI: 1.14-1.79), with sofpironium associated with highest risk of dry mouth and glycopyrronium with highest risks for mydriasis and constipation.</p><p><strong>Conclusions: </strong>Topical anticholinergic agents are effective for PAH treatment, with distinct efficacy and safety profiles. Although the available evidence is limited by the small number of trials, short follow-up durations, and heterogeneity in outcome reporting, these findings support the role of topical anticholinergic therapy as an effective non-invasive option for PAH.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698049","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":"Willingness to Pay for Treatment Attributes in Diffuse Large B-Cell Lymphoma: A Discrete Choice Experiment in Japan.","authors":"Yasuyuki Arai, Timothy Bolt, Hikaru Onishi, Michael LoPresti, Victoria Arguissain, Jörg Mahlich","doi":"10.1007/s40261-026-01549-9","DOIUrl":"https://doi.org/10.1007/s40261-026-01549-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Treatment decision-making in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) is increasingly complex, especially with the emergence of novel, high-cost therapies such as chimeric antigen receptor (CAR) T-cell therapy. Understanding how physicians weigh various clinical and nonclinical treatment attributes is essential for aligning healthcare decisions with both clinical value and economic sustainability. This study aims to quantify Japanese physicians' preferences in health outcomes and patient experience outcomes through eliciting trade-offs in a choice experiment for specific treatment characteristics in R/R DLBCL.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We performed a discrete choice experiment (DCE) with Japanese hematologists and oncologists. Participants completed an online best-worst scaling three alternative discrete choice experiment featuring a series of hypothetical treatment outcomes for DLBCL. The DCE included two patient vignettes: patient Q, a 70-year-old male with two prior treatment lines and Eastern Cooperative Oncology Group (ECOG) performance status 1; and patient R, a 58-year-old female with three prior treatment lines and ECOG performance status 2. Predefined attributes included: overall survival (OS) rates at 12 and 24 months, change in ECOG status at 6 months, CAR-T related side effects (risk of severe cytokine release syndrome (CRS), and risk of severe neurological events), duration of hospitalization, time until treatment initiation, and total treatment cost. A conditional logit model was used to calculate odds ratios (OR) for each attribute's influence on selecting the preferred treatment recommendation. ORs were translated into willingness-to-pay (WTP) estimates for the health outcomes, changes in adverse event risks and waiting time/hospitalization duration.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 231 Japanese hematologists and oncologists participated, each making six treatment decisions for two patient vignettes. Across both profiles, 12- and 24-month overall survival (OS), hospitalization duration, waiting time, and treatment cost significantly influenced preferences. For patient Q, reduced CRS risk was significant, while for patient R, ECOG improvement was influential. Willingness to pay (WTP) for a 1% increase in 24-month OS was approximately JPY 1.4 million (~USD 9520) for patient Q and JPY 1.8 million (~USD 12,240) for patient R; corresponding estimates for 12-month OS were slightly lower. A 1-week reduction in hospital stay was valued at JPY 1.1-1.9 million (USD 7480-12,920), and a 1-week reduction in waiting time at JPY 600,000-1.5 million (USD 4080-10,200). Overall, physicians prioritized long-term survival more strongly for the younger, more severe patient, whereas preferences were more balanced for the older patient. Clinical improvement (ECOG) weighed more heavily for the younger patient, while safety concerns were more salient in the older case.&lt;/p&gt;","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147653826","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":"Comparative Sensory Evaluation of Pediatric Liquid Omeprazole Formulations Available in the UK.","authors":"Sejal R Ranmal, Elisa Alessandrini, Catherine Tuleu","doi":"10.1007/s40261-026-01548-w","DOIUrl":"https://doi.org/10.1007/s40261-026-01548-w","url":null,"abstract":"<p><strong>Background: </strong>Omeprazole is a widely prescribed proton pump inhibitor used to treat gastroesophageal reflux disease and other acid-related disorders in children. Despite its clinical importance, the availability of licensed liquid formulations varies worldwide, often resulting in the use of extemporaneously compounded preparations. These liquid products have varying sensory characteristics that can influence patient acceptability.</p><p><strong>Methods: </strong>A randomized, single-blind sensory evaluation study was conducted with a panel of 30 adult volunteers (aged 24 ± 2.6 years; 77% female) to assess the palatability of six omeprazole liquid formulations available in the UK. Participants rated taste, aftertaste, smell, and mouthfeel aversiveness using a visual analog scale, overall acceptability using a 5-point facial hedonic scale, and provided qualitative feedback.</p><p><strong>Results: </strong>The compounded 8.4% sodium bicarbonate suspension had a significantly more aversive taste (mean ± standard deviation: 74 ± 31; median [interquartile range]: 83 [63-100]) and aftertaste (55 ± 33; 61 [23-80]) compared with all licensed formulations (p < 0.001), with bitterness being a prominent attribute. The licensed menthol-flavored 10-mg/15-mL oral solution received the lowest taste aversiveness rating (17 ± 23; 6 [1-19]), and the highest overall acceptability. Other licensed formulations were generally rated as mild to moderately aversive, with some irritating or burning sensations also reported.</p><p><strong>Conclusions: </strong>A sensory analysis revealed clear differences between compounded and licensed omeprazole formulations, highlighting the importance of developing and prescribing palatable age-appropriate formulations for pediatric populations.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608328","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 Field-Based Cost-Effectiveness Study of Aflibercept and Bevacizumab in Treat-and-Extend Versus Pro Re Nata Protocols for Diabetic Macular Edema in Iraq.","authors":"Rawaa M Jabbar, Ali Azeez Al-Jumaili, Aymen D Jaafar, William R Doucette","doi":"10.1007/s40261-026-01527-1","DOIUrl":"10.1007/s40261-026-01527-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Diabetic macular edema (DME) is a leading cause of vision impairment in individuals with diabetes, often treated with anti-vascular endothelial growth factor (anti-VEGF) therapies, such as Avastin&lt;sup&gt;®&lt;/sup&gt; (bevacizumab) and Eylea&lt;sup&gt;®&lt;/sup&gt; (aflibercept). The study objective is to assess the cost-effectiveness of bevacizumab and aflibercept under treat-and-extend (T&E) and pro re nata (PRN) regimens in managing DME in a real-world clinical setting.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A field-based retrospective study was conducted at a public tertiary eye hospital in Baghdad, Iraq, from October 2024 through March 2025. The study employed a retrospective design, extracting clinical and treatment data from patients' medical records. Additional economic and sociodemographic information was collected through face-to-face interviews conducted by the first author between October 2024 and March 2025. A total of 394 adult patients with DME were included and categorized into six groups; two loading doses groups (LD)-LD Avastin (n = 206) and LD Eylea (n = 188)-and four maintenance doses (MD) groups-T&E Avastin (n = 139), T&E Eylea (n = 124), PRN Avastin (n = 67), and PRN Eylea (n = 64). Clinical outcomes included best-corrected visual acuity (BCVA; measured as logarithm of the minimum angle of resolution [log MAR]) and central macular thickness (CMT). Costs were calculated from the payer's perspective, incorporating medication, and patient costs. Incremental cost-effectiveness ratios (ICERs) were computed for each regimen.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The study included 394 patients, each with one eye affected by DME, categorized into six groups. Based on the chosen LD, 206 patients received six monthly LD of Avastin, and 188 patients received five monthly LD of Eylea. Thereafter, on the basis of the maintenance treatment regimen chosen (MD), 67 patients were assigned to the PRN Avastin treatment group, 64 patients were assigned to the PRN Eylea treatment group, 139 patients were assigned to the T&E Avastin group, and 124 patients were assigned to the T&E Eylea group. During the loading phase, Eylea LD achieved a significantly greater mean utility gain than Avastin LD (0.0909 ± 0.0117 versus 0.0221 ± 0.0106; p = 0.0001). In the maintenance phase, both T&E regimens provided significantly higher utility gains than PRN strategies. PRN Avastin yielded the lowest utility gain (0.0066 ± 0.0072), while PRN Eylea showed modest improvement (0.0278 ± 0.0148; p = 0.0001). Despite superior utility outcomes, Eylea-based regimens exceeded the willingness-to-pay threshold, whereas T&E Avastin remained the most cost-effective option.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The study suggests that Avastin under the T&E regimen is the most cost-effective treatment for DME, providing significant savings while maintaining effective management of the condition. These findings can guide therapeutic decision-making for DME in resource","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"429-445"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147270003","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":"Missed Opportunities in the Therapeutic Patterns of Chronic Obstructive Pulmonary Disease: A Real-World Italian Study on the Impact of Severe Exacerbation on Mortality and Hospital Re-admission.","authors":"Giulia Ronconi, Letizia Dondi, Leonardo Dondi, Silvia Calabria, Irene Dell'Anno, Ovidio Brignoli, Fabiano Di Marco, Claudio Micheletto, Nello Martini, Carlo Piccinni","doi":"10.1007/s40261-026-01534-2","DOIUrl":"10.1007/s40261-026-01534-2","url":null,"abstract":"<p><strong>Background and objectives: </strong>Patients experiencing severe exacerbation (SE) of chronic obstructive pulmonary disease (COPD) face high re-hospitalization and mortality rates. Knowing their impact on health services is crucial for making decisions and improving the care pathway for these patients. To describe mortality, re-hospitalizations and therapeutic patterns of patients experiencing SE, this study used real-world Italian administrative data and examined pre- and post-SE treatment patterns.</p><p><strong>Methods: </strong>From an Italian administrative database (4.6 million inhabitants), patients with COPD in 2022 were identified, and those experiencing SE requiring hospitalization were described in terms of demographics, comorbidities, 12-month mortality and re-hospitalization rates, and therapeutic patterns during 12 months pre- and post-SE. Treatment patterns included dispensations of single-inhaler (SI, i.e., fixed-dose combination) triple therapy (TT), multiple-inhaler (MI, i.e., open combination) TT, dual therapy (DT; based on combinations between inhaled corticosteroid/long-acting beta-agonist/muscarinic antagonist), other respiratory treatment strategies, and no treatment.</p><p><strong>Results: </strong>Among 81,571 patients with COPD (32.1 per 1000 inhabitants aged ≥ 45 years), patients experiencing SE were 6.2% (5080 patients with COPD): mean age was 77 years, 63.4% (3220 patients with SE) were male and 68.2% (3467 patients with SE) had ≥ 3 comorbidities. Mean in-hospital length of stay was 11.9 days. One-year mortality rate was 25.6% (1302 patients with SE), mainly within the first month, 76.0% (989 deaths) of which occurred in hospital. Among 12-month analysable patients (3778), the 12-month re-hospitalization rate was 20.1% (761 patients with SE and alive) occurring, on average, at 155 days (16.4% within the first month). Pre/post SE, single-inhaler triple therapy (SI-TT) and multiple-inhaler triple therapy (MI-TT) increased from 1.4 to 23.4% and from 1.2 to 6.3% patients, respectively; DT, other strategies, and no treatment reduced from 24.5 to 22.5%, 35.7 to 23.8% and 37.1 to 24.0%, respectively. On average, TT was initiated at ≥ 31 days post-SE. Mean time to TT initiation was approximately 31-42 days depending on prior therapy, although most patients initiated TT within the first 30 days.</p><p><strong>Conclusion: </strong>A substantial proportion of patients experiencing SE of COPD were re-hospitalised or remained inadequately treated or untreated, despite a high mortality rate. These findings underscore the necessity for a more appropriate and prompt therapeutic intervention.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"415-427"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147324737","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}