Clinical Drug Investigation最新文献

{"title":"SDZ-AFL: An Aflibercept Biosimilar.","authors":"Yahiya Y Syed","doi":"10.1007/s40261-025-01458-3","DOIUrl":"10.1007/s40261-025-01458-3","url":null,"abstract":"<p><p>SDZ-AFL (SOK583A1; Afqlir^®) is a biosimilar of the reference intravitreal aflibercept, a vascular endothelial growth factor inhibitor. SDZ-AFL has been approved in the EU for the treatment of the same indications in adults as reference aflibercept: neovascular age-related macular degeneration (nAMD), visual impairment due to macular oedema secondary to retinal vein occlusion, visual impairment due to diabetic macular oedema and visual impairment due to myopic choroidal neovascularisation. SDZ-AFL has similar physicochemical and pharmacodynamic properties to those of reference aflibercept, and pharmacokinetic similarity has been demonstrated in patients with nAMD. SDZ-AFL demonstrated clinical efficacy equivalent to that of reference aflibercept in patients with nAMD and was generally well tolerated in this population. The tolerability, safety and immunogenicity profiles of SDZ-AFL were similar to those of reference aflibercept. The role of reference aflibercept in the management of neovascular retinal diseases is well established, and SDZ-AFL provides an effective biosimilar alternative for patients requiring ophthalmic aflibercept therapy.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"677-680"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697805","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":"Relative Bioavailability of Single-Dose Oral Administration of Two SHR7280 Formulations (Dry Suspension and Tablets) in Healthy Chinese Volunteers.","authors":"Xian Liu, Ruzhai Qin, Chang Shu, Kai Shen, Xi Li, Lingyu Ma, Xiaomei Li, Lanping Li, Jiao Peng, Dongxiang Huang, Sihan Chen, Zhihong Xie, Lika Ye, Lian Duan","doi":"10.1007/s40261-025-01470-7","DOIUrl":"10.1007/s40261-025-01470-7","url":null,"abstract":"<p><strong>Background: </strong>SHR7280 is an oral small-molecule gonadotropin-releasing hormone (GnRH) antagonist that can be developed as therapeutic agent for the treatment of hormone-dependent pathologies, including prostate, breast, and ovarian cancers. SHR7280 dry suspension formulation is being developed to provide an alternative mode of administration for order patients, those using nutritional tubes, and those unable to swallow solid dosage forms.</p><p><strong>Objective: </strong>This study evaluated the relative bioavailability, pharmacokinetics (PK), and safety of SHR7280 dry suspension and tablets administered in a single dose in healthy Chinese volunteers.</p><p><strong>Methods: </strong>A randomized, open, two-preparation, two-sequence, two-cycle, double-crossover design was used in this study. The plasma drug concentration was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main PK parameters of the two formulations of SHR7280 were calculated by noncompartmental analysis using Phoenix WinNonlin (version 8.3.4) software. A total of 16 healthy participants were randomized to receive SHR7280 (200 mg) as tablets (n = 8) or dry suspension (n = 8) formulation.</p><p><strong>Results: </strong>The geometric least squares mean ratio (90% confidence interval [CI]) for maximum concentration of drug in blood plasma (C_max) and area under the plasma concentration-time curve from time 0 to t (AUC_0-t) and from time 0 to infinity (AUC_0-∞) between the dry suspension of SHR7280 and its tablets were calculated as follows: C_max-101.90% (90% CI 79.50-130.62), AUC_0-t-111.58% (90% CI 91.71-135.76), and AUC_0-∞-111.44% (90% CI 91.70-135.43). A total of nine (56.3%) subjects experienced treatment-emergent adverse events (TEAEs).</p><p><strong>Conclusions: </strong>The bioavailability of SHR7280 tablets was found to be comparable to that of dry suspension. The safety profile of two formulations was favorable. No serious adverse events or adverse drug reactions were reported.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT05868057; 22 May 2023).</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"643-650"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144798350","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":"Spontaneous Reports of Adverse Reactions with Fatal Outcomes After COVID-19 Vaccination During the National Vaccination Campaign in Sweden.","authors":"Marja-Leena Nurminen, Per Lindemo, Anders Sundström, Björn Zethelius, Maria Larsson, Sofia Attelind, Nicklas Pihlström, Rickard Ljung, Veronica Arthurson","doi":"10.1007/s40261-025-01466-3","DOIUrl":"10.1007/s40261-025-01466-3","url":null,"abstract":"<p><strong>Background and objectives: </strong>Reports of suspected adverse drug reactions are of a great importance for the safety monitoring of new vaccines to identify potential safety risks promptly and to ensure necessary measures for risk mitigation. We reviewed the reports of fatal adverse drug reactions after coronavirus disease 2019 (COVID-19) vaccination with Comirnaty^®, Spikevax^®, and Vaxzevria^® during the national vaccination campaign in Sweden.</p><p><strong>Methods: </strong>Swedish reports of suspected adverse drug reactions with fatal outcomes after COVID-19 vaccines were retrieved from the EudraVigilance database. Vaccination data were obtained from the National vaccination register. Reporting rates were calculated by dividing the number of adverse drug reaction reports with fatal outcomes by the number of people exposed to at least one dose of the COVID-19 vaccines or by the number of vaccine doses given. A causality assessment of adverse drug reaction reports was performed by clinically qualified reviewers.</p><p><strong>Results: </strong>More than 26 million doses of COVID-19 vaccines were administered and 456 reports of suspected adverse drug reactions with fatal outcomes were reported during 27 December, 2020-31 May, 2023. The reporting rate was 5.7 fatal outcomes per 100,000 persons vaccinated with at least one dose of any COVID-19 vaccine or 1.7 per 100,000 vaccine doses given. Most of the fatalities were related to patients' pre-existing conditions, predominantly among people aged 70 years or older. Only ten of the reported fatalities (0.1 per 100,000 persons vaccinated) were assessed as consistent with a causal association to COVID-19 vaccination.</p><p><strong>Conclusions: </strong>Adverse drug reactions with fatal outcomes after COVID-19 vaccines in Sweden were very rare. No new safety concerns were observed in this study.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"665-675"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144834337","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":"Impact of Extracorporeal Membrane Oxygenation Life Support on Vancomycin Population Pharmacokinetics in Critical Illness: A Systematic Review.","authors":"Fatima Khalifa Al-Sulaiti, Esra Demirtürk, Selma Sahin","doi":"10.1007/s40261-025-01449-4","DOIUrl":"10.1007/s40261-025-01449-4","url":null,"abstract":"<p><strong>Background: </strong>An extracorporeal membrane oxygenation (ECMO) device represents an additional functional body compartment, potentially impacting vancomycin pharmacokinetics.</p><p><strong>Objectives: </strong>This systematic review aimed to: (1) provide a comprehensive summary of vancomycin population pharmacokinetics (Pop-PK) in critically ill patients receiving ECMO and; (2) associate the findings with clinical practices and dosing recommendations.</p><p><strong>Methods: </strong>PubMed, Embase and Google Scholar databases were searched for vancomycin non-linear mixed-effects modelling Pop-PK studies in ECMO patients (inception-May 2024). Standardized, pre-tested and pilot-tested tools were used for quality assessment and data extraction utilizing triangulation. Summary measures included typical values for vancomycin pharmacokinetic parameters, influential covariates, and associated interindividual and residual variabilities.</p><p><strong>Results: </strong>Seven studies reporting an approximate total of 1600 vancomycin blood concentrations (range: 33-433 concentrations per study) collected from 215 patients (range: 11-93 patients per study) were included. Pop-PK models fitted three-compartment (n = 1), two-compartment (n = 5), or one-compartment (n = 1) models. Various modalities [venovenous-ECMO (n = 6); venoarterial-ECMO (n = 5), centrifugal-pump (n = 6), roller pump (n = 1)] and age groups were reported [pediatrics (n = 2); adults (n = 6)]. Vancomycin clearance and central volume of distribution (V₁) ranged between 0.0579-4.32 L/h and 0.13-3.32L/kg, respectively. Relatively high between-subject variability (BSV) exists (clearance: 0.1%-77%; V₁: 0.33%-94.8%). Models failed to explain maximally 19.4% of the overall variations, successfully explaining at least 80.6% of the variabilities in vancomycin disposition in ECMO. Age and body weight were significant covariates on clearance and V₁. Additionally, glomerular filtration rate, serum creatinine, creatinine clearance, and use of dialysis were significant covariates on clearance. Clinical status-related covariates (i.e., acute physiology and chronic health evaluation II (APACHE-2) score, sequential organ failure assessment (SOFA) score, presence of shock) and ECMO modality-related covariates (pump type/flow rate, ECMO mode) were not significant covariates in the final clearance and V₁ models.</p><p><strong>Conclusion: </strong>This work comprehensively compiles up-to-date population-approach-based dosing simulations and pharmacokinetic models of vancomycin in ECMO, with special focus on influential predictors of vancomycin disposition to guide clinical dosing decisions. Relatively small sample sizes of patients were reported, a limitation that needs to be addressed in future large-scale studies. Observed BSV mandates therapeutic drug monitoring using Pop-PK models and parameters summarized in this work. Large-scale studies are needed ","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"599-626"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12420762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793630","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":"Cost-Effectiveness of Adding Dapagliflozin and Empagliflozin to Standard Treatment for Diabetic Kidney Disease in China.","authors":"Tingting Qiu, Ping Li, Dan Yan","doi":"10.1007/s40261-025-01462-7","DOIUrl":"10.1007/s40261-025-01462-7","url":null,"abstract":"<p><strong>Background: </strong>Dapagliflozin and empagliflozin are emerging as promising treatment options for diabetic kidney disease (DKD).</p><p><strong>Objective: </strong>This study sought to evaluate the cost effectiveness of incorporating dapagliflozin and empagliflozin into the standard treatment for DKD in China.</p><p><strong>Methods: </strong>A Markov model was constructed to evaluate the cost-effectiveness of dapagliflozin and empagliflozin plus standard treatment versus standard treatment alone for DKD treatment from a healthcare perspective. Costs and utility data was obtained from published literatures within the Chinese context. The primary outcome included total cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). GDP per capita of 2023 in China (¥89,358) was utilized as the willingness-to-pay threshold.</p><p><strong>Results: </strong>Compared to standard treatment alone, add-on therapy of dapagliflozin or empagliflozin resulted in a higher total cost than those solely receiving standard treatment (+¥19,203.56 and +¥9496.92, respectively). However, both dapagliflozin and empagliflozin also yielded more life-years (+1.72 vs. +1.40) and QALYs (+1.40 vs. +0.88). The ICER per life-year and ICER per QALY was ¥11,178.52 and ¥18,192.50 for dapagliflozin and ¥6773.10 and ¥10,811.64 for empagliflozin, respectively. The incremental net monetary benefit was ¥75,120.54 and ¥68,994.90 for dapagliflozin and empagliflozin, respectively. Sensitivity analysis supported the main findings of the base-case analysis as the cost-effectiveness of dapagliflozin or empagliflozin was sustained for most plausible ranges of parameter values.</p><p><strong>Conclusions: </strong>Considering that the ICER falls below the predefined willingness-to-pay threshold, incorporating dapagliflozin and empagliflozin into standard treatment for DKD is likely to be a cost-effective strategy in China.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"651-664"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625482","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":"Mitomycin Intravesical Solution: First Approval.","authors":"Susan J Keam","doi":"10.1007/s40261-025-01475-2","DOIUrl":"10.1007/s40261-025-01475-2","url":null,"abstract":"<p><p>Mitomycin intravesical solution (ZUSDURI^TM), a hydrogel formulation of the DNA synthesis inhibitor mitomycin, has been developed by UroGen Pharma, Inc. for the treatment of low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) via intravesical instillation. In June 2025, mitomycin intravesical solution was approved for the treatment of recurrent LG-IR-NMIBC in the USA. This article summarizes the milestones in the development of mitomycin intravesical solution leading to this first approval for LG-IR-NMIBC.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945116","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":"Pregabalin and Methadone Plasma Levels in Patients Receiving Methadone Maintenance Treatment: An Observational Study.","authors":"Anat Sason, Miriam Adelson, Shaul Schreiber, Einat Peles","doi":"10.1007/s40261-025-01460-9","DOIUrl":"10.1007/s40261-025-01460-9","url":null,"abstract":"<p><strong>Background and objectives: </strong>The combination of pregabalin and opioid usage is a known risk for fatalities. The pregabalin misuse rate among patients in methadone maintenance treatment (MMT) is reported to be high. However, pregabalin's risk among MMT patients, specifically concerning methadone dose and plasma level, is not yet determined. We aimed to study retention, survival, and whether pregabalin misuse is related to methadone dose and plasma level in MMT patients.</p><p><strong>Methods: </strong>An observational study was conducted on 273 patients at the MMT clinic in Tel Aviv, Israel. Inclusion criteria required having urine drug-screening results for pregabalin when evaluated for methadone plasma levels. Methadone dose and plasma level, drug in urine, sociodemographic, and addiction variables were taken from patients' records.</p><p><strong>Results: </strong>Patients with positive urine for pregabalin (n = 50) were comparable to 223 negative patients tested in methadone dose (124.3 ± 30.7 vs. 117.1 ± 42.5, p = 0.3) but had higher methadone plasma levels (693.8 ± 327.6 vs. 572.3 ± 286.5 ng/ml, p = 0.009) and QTc intervals on ECG (422.8 ± 31.8 vs. 412.1 ± 29.8 ms, p = 0.03). Logistic regression model found pregabalin tested positive as more likely to test positive for benzodiazepine (OR = 9.1), methylphenidate (OR = 5.5), and fentanyl (OR = 5.9), and to have higher methadone plasma levels (OR = 1.002). Cumulative retention (p < 0.001) and survival (p = 0.007) since admission to MMT were both shorter in the pregabalin group.</p><p><strong>Conclusions: </strong>Patients who tested positive for pregabalin presented high methadone plasma levels, even though they were treated with normal or low methadone doses. This phenomenon highlights the importance of monitoring methadone levels, which is not a routine procedure, to reduce patients' risk.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"575-582"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526686","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 of Pembrolizumab Monotherapy for High Programmed Death Ligand 1 Advanced or Metastatic Non-small Cell Lung Cancer Depends on Long-Term Survivors.","authors":"Zakile A Mfumbilwa, Janneke A Wilschut, Harry J M Groen, Valesca P Retèl, Bram Ramaekers, Manuela Joore, Veerle M H Coupé","doi":"10.1007/s40261-025-01456-5","DOIUrl":"10.1007/s40261-025-01456-5","url":null,"abstract":"<p><strong>Background: </strong>Pembrolizumab shows effectiveness in treating metastatic non-small cell lung cancer (metNSCLC), with a subgroup of patients experiencing long-term survival (LTS) benefits. The existence of a LTS subgroup may influence the cost-effectiveness of pembrolizumab monotherapy compared with platinum-based chemotherapy. This study aims to assess the potential implications of such a subgroup on the cost-effectiveness for patients with non-squamous metNSCLC and PD-L1 ≥ 50% who are ineligible for targeted therapies.</p><p><strong>Methods: </strong>This study used a decision analytic model based on Dutch real-world data (2008-2014). Two strategies were simulated: (1) a chemotherapy strategy: patients receive chemotherapy in the first-, second-, and third-line; and (2) a pembrolizumab strategy: patients receive first-line pembrolizumab followed by chemotherapy for those progressing to second- and third-lines. The pembrolizumab strategy is evaluated with and without the assumption that there is a LTS subgroup. The LTS subgroup is assumed to be free from metNSCLC-related progression after treatment. Costs (2022 €), including drug costs, other direct medical costs, family costs, and healthcare costs in life years gained, are considered from first-line treatment to death. Effects are measured in quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) is assessed using an €80,000/QALY threshold. Threshold analyses are performed on the size and mortality rate of the LTS subgroup and on the price of pembrolizumab.</p><p><strong>Results: </strong>QALYs per patient were 0.65 for chemotherapy, 1.24 for pembrolizumab without LTS, and 3.52 for pembrolizumab with LTS. Average costs per patient were €58,800 for chemotherapy, €154,600 for pembrolizumab without LTS, and €178,600 for pembrolizumab with LTS. Pembrolizumab without LTS was not cost-effective compared with chemotherapy (ICER €167,600/QALY), but pembrolizumab with LTS (30% of simulated population) was cost effective (ICER of €43,100/QALY). Threshold analyses showed that a LTS subgroup size of at least 10% or halving the price of pembrolizumab was needed for pembrolizumab to be cost-effective.</p><p><strong>Conclusions: </strong>Pembrolizumab is a cost-effective first-line treatment for patients with metNSCLC and PD-L1 ≥ 50% in the Netherlands when at least 10% of patients are long-term survivors. Without long-term survivors, this treatment is not cost-effective. Therefore, it is crucial to consider long-term survivors in assessing the cost-effectiveness of immunotherapy in metNSCLC.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"583-598"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590538","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":"Efficacy and Safety of Biosimilar CT-P47 Versus Reference Tocilizumab: 1-Year Results of a Randomised, Active-Controlled, Double-Blind, Phase III Study in Patients with Rheumatoid Arthritis.","authors":"Gerd Burmester, Jakub Trefler, Artur Racewicz, Janusz Jaworski, Agnieszka Zielińska, Marek Krogulec, Sławomir Jeka, Rafał Wojciechowski, Katarzyna Kolossa, Anna Dudek, Magdalena Krajewska-Włodarczyk, Paweł Hrycaj, Piotr Adrian Klimiuk, SungHyun Kim, JeeHye Suh, GoEun Yang, YunAh Kim, YooBin Jung, GaHee Park, Josef S Smolen","doi":"10.1007/s40261-025-01453-8","DOIUrl":"10.1007/s40261-025-01453-8","url":null,"abstract":"<p><strong>Background and objective: </strong>This phase III study conducted in 22 centres in Poland assessed the efficacy equivalence of candidate tocilizumab biosimilar, CT-P47, and European Union-approved reference tocilizumab (r-TCZ) in rheumatoid arthritis. We report 1-year data, including switching from r-TCZ to CT-P47.</p><p><strong>Methods: </strong>This active-controlled, double-blind, multicentre trial randomised (1:1) adults (aged 18-75 years) with moderate-to-severe rheumatoid arthritis diagnosed for ≥ 24 weeks and treated with methotrextate for ≥ 12 weeks before the first study drug administration, to receive CT-P47 or r-TCZ every 4 weeks (8 mg/kg, intravenous) up to week 20. At week 24, those on CT-P47 continued maintenance treatment; those on r-TCZ were re-randomised (1:1) to continue r-TCZ (r-TCZ maintenance) or to switch to CT-P47 (CT-P47 switched) until week 48 (Treatment Period 2). After week 48, patients were followed up until week 52 (end of study). Efficacy, pharmacokinetics, safety and immunogenicity were evaluated.</p><p><strong>Results: </strong>In Treatment Period 2, 225 patients continued CT-P47 maintenance, 109 continued r‑TCZ maintenance and 110 switched to CT-P47. During Treatment Period 2, efficacy findings were comparable between groups. At week 52, the mean change from baseline in Disease Activity Score in 28 joints-erythrocyte sedimentation rate was - 4.279, - 4.231 and - 4.376 in the CT-P47 maintenance, r-TCZ maintenance and CT-P47 switched groups, respectively. Joint damage progression over 1 year was minimal in all groups. Drug serum concentrations were relatively consistent throughout Treatment Period 2. The safety profile and antidrug antibody-positive conversion rate (< 5% in each group) were similar between groups.</p><p><strong>Conclusions: </strong>Week 52 results show maintained efficacy after switching from r-TCZ to CT-P47, and comparable efficacy, pharmacokinetics, safety and immunogenicity of CT-P47 versus r-TCZ over 1 year of treatment.</p><p><strong>Clinical trial registration: </strong>NCT05489224, 24 July 2022.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"551-563"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144616551","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":"Cost-Effectiveness Analysis of Toripalimab Plus Axitinib for Patients with Advanced Renal Cell Carcinoma in the United States.","authors":"Ibrahim Alfayoumi, Asmita Priyadarshini Khatiwada, Surachat Ngorsuraches","doi":"10.1007/s40261-025-01464-5","DOIUrl":"10.1007/s40261-025-01464-5","url":null,"abstract":"<p><strong>Objective: </strong>The RENOTORCH trial found that toripalimab plus axitinib extended progression-free and overall survival in patients with advanced renal cell carcinoma (RCC), though its financial burden may limit widespread use. This study aimed to assess the cost-effectiveness of toripalimab plus axitinib compared with sunitinib monotherapy as a first-line therapy for patients with previously untreated or intermediate- or poor-risk advanced RCC from a US third-party payer perspective.</p><p><strong>Methods: </strong>A three-state partitioned survival model (progression-free, progression, death) was utilized, with clinical outcomes obtained from the RENOTORCH trial. Progression-free survival (PFS) and overall survival (OS) were modeled using various parametric functions over a 5-year horizon, applying a 3% annual discount rate. Costs of treatments, administration, monitoring, and management of grade 3/4 adverse events (≥ 5% occurrence) were sourced from Micromedex® and Centers for Medicare & Medicaid Services (CMS) databases. Life years (LY), quality-adjusted life years (QALY), and incremental costs per LY and QALY were estimated. One-way and probabilistic sensitivity analyses were conducted. Subgroup analyses for intermediate- and poor-risk patients, as classified by the International Metastatic RCC Database Consortium (IMDC) criteria, were performed using similar methods.</p><p><strong>Results: </strong>Toripalimab plus axitinib increased total costs by $332,359, gained 0.68 LY and 0.36 QALY compared with sunitinib, resulting in incremental costs of $489,747 per LY and $923,962 per QALY. One-way sensitivity analysis showed that the incremental cost per QALY was most sensitive to changes in toripalimab plus axitinib's cost. At a $150,000 willingness-to-pay threshold, probabilistic sensitivity analysis showed a nearly 0% probability of toripalimab plus axitinib being cost-effective. Similarly, toripalimab plus axitinib was still not cost-effective for intermediate- and poor-risk patients.</p><p><strong>Conclusions: </strong>Compared with sunitinib monotherapy, our study suggested that toripalimab plus axitinib was not cost-effective for patients with advanced renal cell carcinoma from a US third-party payer perspective. Further analyses are warranted when more data are available. Despite benefits across different risk groups, toripalimab plus axitinib was not cost-effective for intermediate- and poor-risk patients.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"537-549"},"PeriodicalIF":2.7,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667247","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}