Clinical Drug Investigation最新文献

{"title":"Effects of Ensitrelvir on the Pharmacokinetics of Combined Oral Contraceptives (Ethinyl Estradiol/Drospirenone) in Healthy Adult Women: A Phase 1 Fixed-Sequence, Multiple-Dose, Drug-Drug Interaction Study.","authors":"Ryosuke Shimizu, Risa Yokokawa Shibata, Ryuji Kubota, Sho Okuda, Takuhiro Sonoyama","doi":"10.1007/s40261-026-01541-3","DOIUrl":"10.1007/s40261-026-01541-3","url":null,"abstract":"<p><strong>Background and objective: </strong>Ensitrelvir has shown cytochrome P450 3A (CYP3A) inhibitory/induction potential in in vitro studies. This open-label, fixed-sequence Phase 1 study evaluated potential drug-drug interactions between ensitrelvir and a combined oral contraceptive (COC) containing ethinyl estradiol (EE) and drospirenone in healthy women of childbearing age.</p><p><strong>Methods: </strong>Healthy premenopausal women received EE/drospirenone (0.02 mg/3 mg) on days 1-24. Ensitrelvir was co-administered on day 20 (375 mg) and days 21-24 (125 mg/day). Blood samples were collected on days 19, 20, and 24 to assess plasma EE, drospirenone, and ensitrelvir concentrations. The primary endpoint was evaluation of the maximum plasma concentration, time to maximum plasma concentration, and area under the plasma concentration-time curve over the dosing interval τ (AUC_0-τ) assessed using noncompartmental methods. Treatment-emergent adverse events (TEAEs) were recorded for safety assessments.</p><p><strong>Results: </strong>The safety and pharmacokinetic parameter population comprised 24 and 23 participants, respectively. Compared with day 19, AUC_0-τ ratios on days 20 and 24 were 1.02- and 1.07-fold for EE and 1.10- and 1.80-fold for drospirenone, respectively. This result suggested the inhibitory potential for CYP3A to be likely weaker on the first day than on the last day. Ensitrelvir AUC_0-τ was higher on day 24 versus day 20 and comparable with that reported previously. Treatment-emergent adverse events occurred in 58.3% of participants, none of which were severe, serious, or led to treatment discontinuation.</p><p><strong>Conclusion: </strong>Ensitrelvir has no clinically meaningful effect on the pharmacokinetics of EE and drospirenone, and the combination was well tolerated. These findings support the co-administration of ensitrelvir with COCs in clinical practice.</p><p><strong>Trial registration: </strong>NCT06775730.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"561-570"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147580472","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":"Urinary MicroRNA Expression and Tacrolimus Pharmacokinetic Variability in Kidney Transplant Recipients: A Cross-sectional Study.","authors":"Nikola Stefanović, Katarina Danković, Radmila Veličković-Radovanović, Marija Vukelić-Nikolić, Maša Jović, Stevan Vujić, Vladana Stojiljković, Branka Mitić, Tatjana Cvetković","doi":"10.1007/s40261-026-01544-0","DOIUrl":"10.1007/s40261-026-01544-0","url":null,"abstract":"<p><strong>Background: </strong>Dysregulation of specific microRNAs and the intraindividual (IPV) and interindividual pharmacokinetic variability of tacrolimus (Tac) have been associated with unfavorable long-term outcomes after kidney transplantation. It remains unknown whether the effects of Tac pharmacokinetic variability are reflected in microRNA expression.</p><p><strong>Objective: </strong>The primary objective was to analyze the correlation between urinary microRNA (miR-21-5p, miR-142-3p, miR-155-5p, and miR-204-5p) relative expression levels in the long term and Tac pharmacokinetic variability parameters within the early period after kidney transplantation. Secondarily, correlation between urinary microRNA expression and long-term graft function were analyzed.</p><p><strong>Methods: </strong>In a cross-sectional study, the urinary microRNA expression levels were determined in 50 kidney transplant recipients in the long-term period after kidney transplantation and in 12 healthy controls. Patients were divided based on the Tac IPV and metabolic phenotype, defined by Tac dose-adjusted concentration (C₀/D) at the 3rd post-transplantation month.</p><p><strong>Results: </strong>Urinary expression of miR-142-3p (p = 0.022) and miR-204-5p (p = 0.007), but not miR-21-5p and miR-155-5p, differed significantly between patients in the long-term post-transplantation period and healthy controls. Patients characterized by fast/intermediate Tac metabolic phenotype had decreased urinary miR-204-5p expression compared to slow metabolizers (p = 0.007; p = 0.005, respectively). Patients with estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m² demonstrated significantly higher log-transformed expression of miR-204-5p compared to those with eGFR < 45 mL/min/1.73 m² (p = 0.003).</p><p><strong>Conclusion: </strong>This study indicated that the urinary expression levels of miR-142-3p and miR-204-5p were significantly different between kidney transplant recipients and healthy controls. Additionally, urinary miR-204-5p expression may be correlated with graft function in the long‑term post‑transplantation period, as well as with early Tac C₀/D values.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"517-530"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572186","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":"Effectiveness of Dexmedetomidine and Sufentanil in Preventing Adverse Reactions to Carboprost Tromethamine During Cesarean Section with Noninvasive Cardiac System Monitoring.","authors":"Jing Li, Bo Xiang, Xiaofeng Lei, Jin Yu","doi":"10.1007/s40261-026-01547-x","DOIUrl":"10.1007/s40261-026-01547-x","url":null,"abstract":"<p><strong>Background and objective: </strong>Carboprost tromethamine is commonly used to prevent or treat postpartum hemorrhage during cesarean section but causes frequent side effects. This study aimed to compare dexmedetomidine and sufentanil for preventing these side effects and assess hemodynamic stability.</p><p><strong>Methods: </strong>This is a single-center randomized controlled trial. Parturients undergoing elective cesarean section were randomized to Group D (dexmedetomidine intravenously), Group S (sufentanil intravenously), and Group C (saline intravenously). Carboprost tromethamine 250 µg was intrauterine injected after delivery. The incidence of complications, Ramsay sedation scores, and noninvasive cardiac system-derived hemodynamic parameters were analyzed. The primary endpoint is dexmedetomidine or sufentanil could relieve the nausea and vomiting caused by carboprost tromethamine.</p><p><strong>Results: </strong>A total of 152 subjects were included in the analysis. Both Groups D and S had significantly fewer intraoperative nausea and vomiting episodes (Group D 16% vs Group S 19.2% vs Group C 76%, P < 0.001) and higher Ramsay scores (P < 0.001) compared with Group C. Group C showed significant increases in mean arterial pressure and respiratory rate (P < 0.05). Heart rate in Group D was significantly lower than in Group C (P < 0.05). The total peripheral resistance was significantly lower in Group S at T2-T5 (from 2 minutes post-carboprost tromethamine until the end of surgery) and in Group D at T2-T4 (2, 5, and 10 minutes post-carboprost tromethamine) compared with Group C (P < 0.05). Cardiac output in Group S was higher at T2-T4 (2, 5, and 10 minutes post-carboprost tromethamine) than in Group C, and at T2-T3 (2 and 5 minutes post-carboprost tromethamine), it was even higher than in Group D (P < 0.05).</p><p><strong>Conclusions: </strong>Both dexmedetomidine and sufentanil alleviated carboprost tromethamine-induced side effects while maintaining stable hemodynamics. Sufentanil showed greater efficacy in reducing peripheral vascular resistance.</p><p><strong>Clinical trial registration: </strong>ChiCTR2000038350.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"551-559"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572184","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-Effectiveness Analysis of PI3K Inhibitors for Relapsed or Refractory Follicular Lymphoma in China: A Comparison Between Linperlisib and Duvelisib.","authors":"Xuefei Bai, Rongjie Shao, Xiaoning He","doi":"10.1007/s40261-026-01532-4","DOIUrl":"10.1007/s40261-026-01532-4","url":null,"abstract":"<p><strong>Background: </strong>Linperlisib, a highly selective PI3K-δ inhibitor, was firstly approved in China in November 2022 for the treatment of patients with relapsed or refractory follicular lymphoma (r/r FL) who had received at least two prior lines of systemic therapy (3L+ FL), demonstrating compelling clinical efficacy.</p><p><strong>Objective: </strong>This study aimed to evaluate the cost effectiveness of linperlisib compared to duvelisib for patients with 3L+ FL from the perspective of Chinese healthcare system.</p><p><strong>Methods: </strong>A lifetime three-state partitioned survival model was developed to integrate comparative efficacy and direct costs. An unanchored matching-adjusted indirect comparison (MAIC) was conducted using individual data from NCT04370405 and published aggregate data from the DYNAMO trial, aiming to derive comparative efficacy data and calculate patients' life-years gained. Utility values were from GADOLIN study, as neither trial collected them. Quality-adjusted life-years (QALYs) were calculated by multiplying life-years by utility values. Direct costs included costs of drug acquisition, adverse events, subsequent salvage therapy, health-care resource use (HCRU), and end-of-life care. A 5% annual discount rate was applied to both future QALYs and costs. The primary outcome was the incremental cost-effectiveness ratio (ICER), calculated as discounted incremental costs divided by incremental QALYs. The willingness-to-pay (WTP) threshold was set at China's 2023 per capita GDP (CNY89,358/QALY), with an ICER below this threshold indicating linperlisib was more cost effective. Model robustness was verified via one-way deterministic and probabilistic sensitivity analyses (DSA and PSA).</p><p><strong>Results: </strong>In the base-case analysis, linperlisib yielded an additional 1.58 QALYs (4.13 vs 2.55) at an incremental cost of CNY108,780 (CNY292,805 vs CNY184,025) compared with duvelisib. The resulting ICER was CNY68,996 per QALY, which was below the WTP. Although drug costs were the main cost driver, improved survival reduced end-of-life care costs by CNY1,507. Deterministic sensitivity analysis identified the price of linperlisib as the top influential parameter, yet all ICERs stayed below the WTP threshold. Probabilistic sensitivity analysis showed a 91.2% cost-effectiveness probability at the preset WTP, confirming robust findings.</p><p><strong>Conclusions: </strong>Linperlisib is cost effective compared to duvelisib for 3L+ FL patients in China, as verified in sensitivity analyses. Further study is warranted to confirm that it meets an unmet need in China.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"571-581"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431246","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":"Alternative Dosing Strategies to Enhance the Absorption of N-Acetyl-D-Mannosamine Monohydrate (ManNAc) in Healthy Adult Males.","authors":"Tahlia R Meola, Kellie La Fontaine, James Condon, Paul Wabnitz, Gianfranco Fornasini, Allan M Evans, Stephanie E Reuter","doi":"10.1007/s40261-026-01546-y","DOIUrl":"10.1007/s40261-026-01546-y","url":null,"abstract":"<p><strong>Background: </strong>GNE myopathy is a rare autosomal recessive muscle disease caused by biallelic mutations in GNE, a gene which encodes the bifunctional enzyme that catalyses the rate-limiting step of intracellular sialic acid biosynthesis. Whilst there is no current marketed therapy to treat the disease, current investigations focus on supplementation with N-acetyl-D-mannosamine monohydrate (ManNAc), a precursor in the biosynthesis of N-acetylneuraminic acid (Neu5Ac), the most abundant sialic acid. ManNAc possesses a low oral bioavailability, likely owing to poor absorption, and exhibits non-linearity across the therapeutic range, possibly due to saturation of intestinal transporter systems.</p><p><strong>Objectives: </strong>The study was conducted to examine if the absorption of ManNAc could be improved by administering a smaller (non-saturating) oral dose, more frequently, or by co-administering ManNAc with dietary salt, which might facilitate carrier-mediated transport.</p><p><strong>Methods: </strong>This was an open-label, randomised, cross-over study in 12 healthy male participants. Participants were administered 4 x 1 g doses of ManNAc every hour, 4 g ManNAc as a single dose with 1 g dietary salt or 4 g ManNAc alone.</p><p><strong>Results: </strong>The pharmacokinetic analysis population comprised 11 participants who received all three study treatments. Administration of ManNAc as split doses, more frequently, resulted in a 1.7-fold increase in ManNAc plasma exposure compared to a single 4 g dose, with a corresponding 1.9-fold increase in systemic Neu5Ac concentrations. In comparison, co-administration of ManNAc with dietary salt had no impact on ManNAc absorption.</p><p><strong>Conclusions: </strong>This study suggests that strategies to slow down the delivery of ManNAc to the small intestine may significantly improve its overall bioavailability and therefore reduce total daily dose requirements.</p><p><strong>Clinical trial registration: </strong>The clinical trial was registered on the Australian New Zealand Clinical Trials Registry (ID: ACTRN12620001127998).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"531-540"},"PeriodicalIF":3.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572689","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":3.1,"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":"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":3.1,"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":"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":3.1,"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":3.1,"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}

{"title":"Global Long-Term Cost Effectiveness of Newer Antidiabetic Drugs for Type 2 Diabetes Mellitus: A Systematic Review.","authors":"Dan Li, Alesha Smith, Carlo A Marra","doi":"10.1007/s40261-026-01530-6","DOIUrl":"10.1007/s40261-026-01530-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;The rising global burden of type 2 diabetes mellitus, compounded by the expanding therapeutic landscape, has placed increasing pressure on health systems to generate robust evidence on the long-term value for money of newer antidiabetic drugs (NADs). This systematic review addresses the urgent need for an updated synthesis of evidence on long-term health economic evaluations of NADs for the treatment of type 2 diabetes, including studies on the latest agents such as tirzepatide and finerenone. It aims to synthesise global long-term cost-effectiveness analyses, assess reporting completeness using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 framework and outline key implications for clinicians, payers and policymakers seeking to optimise type 2 diabetes management within resource-constrained health systems.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;PubMed, Embase, Cochrane, EBSCOhost, Scopus and Web of Science were systematically searched for studies published between 1 January, 2008 and 20 February, 2025. Eligible studies were long-term incremental cost-effectiveness analyses conducted in adults with type 2 diabetes, comparing NADs with other NAD classes or with standard treatment, and reporting outcomes such as incremental cost-effectiveness ratios. A formal risk of bias assessment using tools designed for clinical trials was not undertaken. Instead, reporting quality and transparency were assessed using the CHEERS 2022 checklist, with modelling-related sources of uncertainty and potential bias examined qualitatively. Given the methodological heterogeneity, results were synthesised narratively. Full-text English articles were included. This review was not prospectively registered.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The search identified 1481 records, of which 142 studies met the inclusion criteria. Overall, 81% of incremental cost-effectiveness ratio-based analyses reported that NADs were cost effective compared with conventional therapies under country-specific willingness-to-pay thresholds. Using Thailand as an example of a developing country, studies generally found NADs not to be cost effective, largely because willingness-to-pay thresholds (USD 4336-5310 per quality-adjusted life-year) are substantially lower than those in higher income settings. Recently introduced agents (e.g. tirzepatide and finerenone) and early-line use were typically cost effective only at higher willingness-to-pay thresholds (USD 100,000-150,000 per quality-adjusted life-year) or following substantial price reductions (≥ 70% for sodium glucose cotransporter-2 inhibitors and ≥90% for oral glucagon-like peptide-1 receptor agonists). Most evaluations employed established diabetes models and adopted lifetime horizons from a payer perspective, while reporting quality assessments revealed limited disclosure of stakeholder involvement.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These findings should be interpreted c","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"359-376"},"PeriodicalIF":3.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12999595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147431315","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}