Cts-Clinical and Translational Science最新文献

{"title":"Real-World Evaluation of Outcomes and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Pediatric Patients With Cystic Fibrosis: A Retrospective Study","authors":"Nicola Perrotta,&nbsp;Luigi Angelo Fiorito,&nbsp;Rossella Gentile,&nbsp;Roberta Vescovo,&nbsp;Alfonso Piciocchi,&nbsp;Patrizia Troiani,&nbsp;Roberto Poscia,&nbsp;Giuseppe Cimino","doi":"10.1111/cts.70373","DOIUrl":"10.1111/cts.70373","url":null,"abstract":"<p>Elexacaftor/Tezacaftor/Ivacaftor (ETI) therapy has significantly improved clinical outcomes in people with cystic fibrosis (PwCF) carrying at least one Phe508del CFTR mutation. However, real-world evidence on the safety and effectiveness of ETI in pediatric populations remains limited, particularly in children with more severe disease phenotypes who are often excluded from clinical trials. We analyzed clinical, functional, and microbiological data from pediatric CF patients aged 6–17 years treated with ETI between October 2022 and March 2024. Lung function (ppFEV₁, ppFVC), nutritional status (BMI, BMI <i>z</i>-score), sweat chloride concentration (SwCl), quality of life (CFQ-R), pulmonary exacerbations (PEx), and airway pathogens were assessed at baseline and after 6–12 months. Adverse events (AEs) and therapy discontinuations were also recorded. Twenty-four patients (<i>n</i> = 10 aged 6–11 years; <i>n</i> = 14 aged 12–17 years) were included. At 12 months, mean ppFEV₁ increased by 15% (<i>p</i> = 0.013), BMI by 2.4 kg/m² (<i>p</i> = 0.16), BMI weight z-score by 0.33 (<i>p</i> = 0.63), and height <i>z</i>-score by −0.33 (<i>p</i> = 0.72), SwCl decreased by 46 mmol/L (<i>p</i> &lt; 0.001), and CFQ-R respiratory domain improved by 14 points (<i>p</i> &lt; 0.001). PEx rates decreased by 27.6% after 12 months. Reductions in airway pathogen prevalence, particularly <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, were observed. AEs occurred in 14.8% (<i>n</i> = 4) of patients, were mild-to-moderate, and resolved with dose reduction. ETI therapy was associated with marked improvements in lung function, nutritional status, and quality of life, along with reductions in PEx and airway pathogens, in a real-world pediatric CF cohort. These findings support ETI use in this population, with careful AE monitoring and dose adjustment when needed.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214116","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":"Bridging Implementation Gaps in Digital Health: A Translational Research Imperative for Equitable Healthcare Innovation","authors":"Laiba Husain,&nbsp;Katherine Kitchens,&nbsp;Saroop Raja,&nbsp;Madiha Memon","doi":"10.1111/cts.70375","DOIUrl":"https://doi.org/10.1111/cts.70375","url":null,"abstract":"<p>Digital health technologies' potential to democratize healthcare access appears constrained by implementation challenges that may reproduce existing inequities. This paper examines systemic barriers potentially impeding translation, suggesting prevailing frameworks inadequately address structural determinants. Despite substantial investment, limited FDA approvals for digital-derived endpoints indicate possible regulatory-innovation disjunctures, while constrained funding and incomplete reimbursement structures systematically exclude essential services. We propose a precision implementation framework repositioning implementation science as integral to technological development, potentially challenging linear translational paradigms. This approach emphasizes examining sociotechnical systems, organizational readiness variations, and community-specific contexts. Whether digital health mitigates or exacerbates disparities likely depends on reconceptualizing implementation as socio-organizational transformation requiring regulatory harmonization, sustainable economic models, and equity-centered engagement.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70375","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223983","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":"Trends in and Determinants of Approval Lag for Anticancer Drugs in Japan and the US: Role of Multi-Regional Trials and Concurrent Approvals","authors":"Hitoshi Kanno,&nbsp;Kotone Matsuyama","doi":"10.1111/cts.70336","DOIUrl":"10.1111/cts.70336","url":null,"abstract":"<p>Timely access to treatment for cancer patients requires the accelerated approval of new anticancer therapies. However, the lengthy pharmaceutical approval process in Japan has contributed to what is known as “drug lag.” Although recent efforts to promote international multi-regional clinical trials (MRCTs) involving Japan and to advance strategies for concurrent approval in Japan and the United States have helped shorten time to approval, the individual effects of these approaches have not been fully quantified. This study analyzed trends in the timing of drug application, review, and approval for anticancer agents approved in Japan and the United States, and evaluated the influence of MRCT participation, concurrent approval, company origin, cancer type, and regulatory programs through multivariate analysis. We examined 142 anticancer agents approved between October 2004 and March 2025 by the Pharmaceuticals and Medical Devices Agency in Japan and the U.S. Food and Drug Administration. The median approval lag was 774 days (interquartile range: 217–1370), but decreased markedly to about 100 days by the 2020s. Approval lag was significantly shorter for drugs developed through MRCTs and those approved concurrently in both countries (both <i>p</i> &lt; 0.001), whereas company origin, cancer type, and regulatory program use were not significantly associated (<i>p</i> &gt; 0.05). Multivariate analysis confirmed that MRCTs and concurrent approval were independently associated with shorter approval lag. These findings support early international development and synchronized submission timing to further reduce approval lag. They provide updated evidence based on recent data and offer novel insights by quantifying the effects of MRCT implementation and concurrent approval.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208323","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":"Use of Biomarkers in Drug Development for Regulatory Purposes","authors":"Robert N. Schuck,&nbsp;Vanitha Sekar","doi":"10.1111/cts.70377","DOIUrl":"10.1111/cts.70377","url":null,"abstract":"<p>Appropriately validated biomarkers are important tools that can benefit drug development and regulatory assessments. For drug development purposes, biomarker development involves identifying a drug development need and context of use (COU) for the biomarker, analytically validating assays, clinically validating the biomarker for the COU, and determining if the biomarker provides benefits over current methods. This perspective provides information on determining a biomarker's COU, fit-for-purpose validation, and regulatory acceptance of biomarkers for drug development.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208481","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":"Safety, Pharmacokinetics, and Immunogenicity of Astegolimab, an Anti-ST2 Monoclonal Antibody, in Randomized, Phase I Clinical Studies","authors":"Wenhui Zhang,&nbsp;Dorothy Cheung,&nbsp;Alice Fong,&nbsp;Logan Brooks,&nbsp;Michele A. Grimbaldeston,&nbsp;Audrey Arjomandi,&nbsp;Xiaoying Yang,&nbsp;Ajit Dash,&nbsp;Hansen Wong,&nbsp;Jane R. Parnes,&nbsp;Divya Mohan","doi":"10.1111/cts.70338","DOIUrl":"10.1111/cts.70338","url":null,"abstract":"<p>Astegolimab, a fully human immunoglobulin G2 monoclonal antibody, binds with high affinity to ST2, the interleukin-33 receptor, thereby blocking ST2/interleukin-33 binding and subsequent inflammatory cascades involved in inflammatory diseases. Here, we present three randomized, double-blind, placebo-controlled, Phase I studies evaluating the safety, tolerability, pharmacokinetics, and immunogenicity of single-ascending doses of astegolimab in healthy participants and patients with mild atopic asthma (NCT01928368), multiple-ascending doses in healthy participants (NCT02170337), and single-ascending doses in healthy Japanese and White adults. Overall, 152 participants were enrolled, randomized, and treated with single- or multiple-ascending doses of astegolimab (<i>n</i> = 112) or placebo (<i>n</i> = 40) subcutaneously (2.1–560 mg) or intravenously (210 or 700 mg). No deaths, serious adverse events, or discontinuations due to adverse events occurred during the studies. No clinically meaningful differences in incidence of TEAEs were observed between treatment arms. Pharmacokinetic exposure increased more than dose proportionally over 2.1–420 mg for single-ascending doses but were approximately dose proportional for single- and multiple-ascending doses ≥ 70 mg following subcutaneous administration. No pharmacokinetic differences were observed based on ethnicity between Japanese and White participants following body weight adjustments. Incidence of antidrug antibodies to astegolimab in healthy participants in the single- and multiple-ascending dose studies was 14%–23% and 33%–50% for subcutaneous and intravenous administration, respectively. Astegolimab was well tolerated in these Phase I studies with no safety concerns identified. Thus, further assessment of astegolimab in targeted patient populations was justified; the Phase IIb ALIENTO and Phase III ARNASA trials in patients with chronic obstructive pulmonary disease are ongoing.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70338","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145208372","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 Dose-Escalation Design on the Safety and Development of Anticancer Drugs in Clinical Trials","authors":"Atsushi Nonami,&nbsp;Kensuke Matsuda,&nbsp;Kouta Funakoshi,&nbsp;Ryosuke Kato,&nbsp;Hideaki Takahashi,&nbsp;Yoko Edahiro","doi":"10.1111/cts.70367","DOIUrl":"10.1111/cts.70367","url":null,"abstract":"<p>The operational characteristics of dose-escalation design in phase I studies have been studied using simulations; however, there is limited analysis regarding its effects on the results of clinical trials. We collected the data of 394 clinical trials involving dose-escalation studies for anticancer drugs submitted to the Pharmaceuticals and Medical Devices Agency between 2013 and 2022. We used the internal data of the PMDA and published papers and analyzed outcomes such as enrollment and drug development. We identified model-based designs and rule-based designs as the two primary designs. The median number of dose-limiting toxicity (DLT)-evaluated patients was higher for model-based designs than for rule-based designs. The proportion of rule-based designs was higher in Japanese trials and that of model-based designs was higher in multiregional clinical trials (MRCTs). The determined recommended phase II dose (RP2D) was consistent with the approved dose in all trials (13/13) involving model-based designs and in 84.0% (21/25) of trials involving rule-based designs, although it was not statistically significant. The proportion of progression to the next study phase was 50.0% (61/122) for rule-based designs and 56.3% (36/64) for model-based designs. Similar trends in these outcomes were observed when MRCTs and Japanese trials were examined separately. Model-based designs might require more DLT-evaluated patients; however, they might have different operational capabilities compared with rule-based designs, such as selecting an RP2D consistent with the approved dose. The results might help in selecting the optimal dose-escalation methods in future phase I trials.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12483344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202030","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":"Risk and Association of Specific HLA Alleles With Nintedanib-Induced Gastrointestinal Adverse Reactions: A Discovery Study in an Italian Population","authors":"Stefano Mocci,&nbsp;Roberto Littera,&nbsp;Silvia Deidda,&nbsp;Andrea Perra,&nbsp;Matteo Floris,&nbsp;Sabrina Giglio","doi":"10.1111/cts.70371","DOIUrl":"10.1111/cts.70371","url":null,"abstract":"<p>Idiopathic Pulmonary Fibrosis (IPF) is a progressive and fatal lung disease with limited treatment options. <i>Nintedanib</i> and <i>pirfenidone</i> are the only antifibrotic drugs approved by both the USA and European medicinal agencies, but their efficacy and tolerability remain concerns. This exploratory study investigates the association between genetic variation in the Major Histocompatibility Complex (MHC) region and adverse effects (AEs) of these therapies. HLA genotyping has been previously performed in a discovery cohort of 124 IPF Italian patients, with recorded drug-related AEs. Logistic regression analysis using an additive model identified <i>HLA-C*06:02</i> as a significant risk factor, increasing the likelihood of AEs sixfold in <i>nintedanib</i>-treated patients (<i>p</i> = 0.0043, OR = 6.54, 95% C.I. 1.80–23.75). Notably, gastrointestinal toxicity—the most common AE—was strongly associated with this allele (<i>p</i> = 0.0005, OR = 11.85, 95% C.I. 2.94–47.71). These findings suggest a potential immune-mediated mechanism involving IL-23-driven inflammation and underscore the importance of pharmacogenetic tools in tailoring antifibrotic therapy. Implementing genetic screening could help minimize AEs and improve patient outcomes. Larger studies are warranted to validate these associations and guide personalized treatment strategies.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145187510","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":"Association Between HNP1-3 and Atherosclerotic Plaque Burden in Subclinical Atherosclerosis and the Mediating Effect of PCSK9","authors":"Ece Yurtseven,&nbsp;Kemal Baysal,&nbsp;Said İncir,&nbsp;Ata Alpay Canbaz,&nbsp;Mert Veznikli,&nbsp;Arzu Baygul,&nbsp;Gamze Aslan,&nbsp;Yasemin Demirci,&nbsp;Erol Gursoy,&nbsp;Kayhan Çetin Atasoy,&nbsp;Dilek Ural","doi":"10.1111/cts.70369","DOIUrl":"10.1111/cts.70369","url":null,"abstract":"<p>Subclinical atherosclerosis is a key predictor of cardiovascular events. While inflammation plays a crucial role in atherosclerosis, the involvement of Human Neutrophil Peptides 1–3 (HNP1-3) in its progression remains unclear. The study investigates the association of HNP1-3 and PCSK9 with coronary atherosclerotic burden and explores the potential mediatory role of PCSK9 in HNP1-3's effect on atherogenesis. Patients who underwent coronary computed tomographic angiography (CCTA) and had subclinical atherosclerosis (luminal stenosis &lt; 50%) or normal coronary arteries were included in this cross-sectional study. HNP1-3 and PCSK9 levels were measured using ELISA, and coronary plaque burden was quantified using the modified Gensini score. Patients with subclinical atherosclerosis had significantly higher levels of HNP1-3 (<i>p</i> &lt; 0.001), PCSK9 (<i>p</i> &lt; 0.001), and lipoprotein(a) [Lp(a)] (<i>p</i> &lt; 0.001) compared to controls. HNP1-3 was an independent predictor of subclinical atherosclerosis (<i>p</i> &lt; 0.001), and its levels positively correlated with the modified Gensini score (<i>p</i> &lt; 0.001). In multinomial logistic regression, higher levels of HNP1-3, PCSK9, and Lp(a) were independently associated with higher modified Gensini score tertiles. Mediation analysis revealed that PCSK9 mediated 48.7% of the effect of HNP1-3 on the modified Gensini score. After adjusting for hsCRP and cardiovascular risk factors, the direct effect of HNP1-3 became statistically insignificant, while the indirect effect via PCSK9 remained significant, suggesting that PCSK9 fully mediates the pro-atherogenic effects of HNP1-3. In conclusion, HNP1-3 is a novel independent predictor of subclinical atherosclerosis and coronary plaque burden, with its effects being mediated through PCSK9. These findings suggest that targeting PCSK9 could mitigate the inflammatory actions of HNP1-3, offering potential therapeutic insights for atherosclerosis prevention.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12480437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193944","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":"Pharmacokinetics and Safety of Pelacarsen, a GalNAc3-Conjugated Antisense Oligonucleotide Targeting Apo(a), in Participants With Mild Hepatic Impairment","authors":"Jing-He Yan,&nbsp;Amanda J. Taylor,&nbsp;Timothy Clough,&nbsp;Elise Burmeister-Getz,&nbsp;Marketa Pazdirkova,&nbsp;Cesare Russo","doi":"10.1111/cts.70344","DOIUrl":"10.1111/cts.70344","url":null,"abstract":"<p>Pelacarsen, an antisense oligonucleotide, directly inhibits plasma lipoprotein(a) production; however, it remains unknown whether hepatic impairment (HI) impacts its safety and pharmacokinetics. This single-dose, open-label, parallel-group, phase I study (NCT05026996) assessed the effect of mild HI on the pharmacokinetics, safety, and tolerability of pelacarsen. Participants (aged 18–75 years) with mild HI (<i>n</i> = 8; Child-Pugh Class A) or healthy controls (<i>n</i> = 9; matched for sex, age, and body weight) received a single subcutaneous injection of 80 mg pelacarsen. Pharmacokinetic parameters were determined using non-compartmental methods. Log-transformed pharmacokinetic parameters were analyzed using a statistical model with group and matching covariates as fixed effects. Least-squares geometric means for each group and geometric mean ratios between participants with mild HI and healthy controls were extracted. The geometric mean ratios for pelacarsen maximum observed concentration (<i>C</i>_max), area under the concentration-time curve from time 0 to time of last quantifiable concentration (AUC_last), and AUC from time 0 to infinity (AUC_inf) were, on average, 7%, 37%, and 50% higher, respectively, in participants with mild HI versus matched controls. The corresponding between-participant variability estimates ranged from 43.0% to 55.2%. The mean elimination half-life (<i>T</i>_1/2) was comparable between the two groups (mild HI, 533 h; healthy matched controls, 518 h). No safety concerns were identified in participants with mild HI or in matched controls. Overall, pelacarsen was well tolerated, and mild HI had no significant effect on <i>C</i>_max. The increase in AUC, likely due to slower early-phase disposition, was within the exposure range tested in the first-in-human study and considered safe.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193949","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 of Statins for Oxaliplatin-Induced Peripheral Neuropathy: A Multicenter Retrospective Observational Study","authors":"Kenshi Takechi,&nbsp;Takehiro Kawashiri,&nbsp;Keisuke Mine,&nbsp;Soichiro Ushio,&nbsp;Hirofumi Hamano,&nbsp;Noriko Hida,&nbsp;Kenji Momo,&nbsp;Masanobu Uchiyama,&nbsp;Mami Uchida,&nbsp;Mamoru Tanaka,&nbsp;Noriaki Hidaka,&nbsp;Hideki Yasui,&nbsp;Masahiro Ueda,&nbsp;Ryohei Fujii,&nbsp;Misaki Hashimoto,&nbsp;Yasutaka Sakamoto,&nbsp;Kana Uyama,&nbsp;Takahiro Niimura,&nbsp;Yuki Hanai,&nbsp;Ayaka Tsuboya,&nbsp;Keisuke Suzuki,&nbsp;Naoya Kamiyama,&nbsp;Hiromi Hagiwara,&nbsp;Naoto Okada,&nbsp;Yoshito Zamami,&nbsp;Keisuke Ishizawa","doi":"10.1111/cts.70318","DOIUrl":"10.1111/cts.70318","url":null,"abstract":"<p>Chemotherapy-induced peripheral neuropathy, including oxaliplatin-induced peripheral neuropathy (OIPN), can have a negative impact on patient quality of life for months or even years after discontinuation of chemotherapy. Statins are commonly used for lowering cholesterol; however, evidence indicates that statins have multiple pleiotropic effects. Although statins are anticipated to exert neuroprotective actions against OIPN, no large-scale investigations have been conducted in real-world clinical settings. Our investigation aimed to determine if statins protected against OIPN. This multicentre retrospective study enrolled Japanese patients with cancer, including those with colorectal cancer (CRC), who received oxaliplatin-containing chemotherapy between April 2009 and December 2019. Propensity score matching between groups was performed to assess the relationship between the occurrence of OIPN and statin use. Among the examined 2657 patients receiving oxaliplatin, 24.7% had Grade ≥ 2 OIPN. There was no significant difference in the incidence of OIPN between the statin and non-statin groups, even after propensity score matching. However, among the matched patients with CRC (<i>n</i> = 510), statin use was associated with a significantly lower incidence of Grade ≥ 2 OIPN than no statin use (19.8% vs. 28.3%, respectively; <i>p</i> = 0.029). Our findings indicate that statins may protect against OIPN in patients with CRC.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12478450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193882","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}