Clinical therapeutics最新文献

{"title":"Differential Effects of Anti-Seizure Medications on Sarcopenia in Patients With Epilepsy.","authors":"Yu-Shiue Chen, Ming-Chi Lai, Huai-Chun Huang, Huai-Ying Ingrid Huang, Chin-Wei Huang","doi":"10.1016/j.clinthera.2025.09.014","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.014","url":null,"abstract":"<p><strong>Purpose: </strong>Epilepsy is a chronic neurological disorder that often requires long-term use of anti-seizure medications (ASMs). While ASMs are known to affect bone health, their impact on muscle mass and the development of sarcopenia has not been well studied. This study investigated the association between ASM use and sarcopenia in patients with epilepsy and identified specific medications associated with increased risk.</p><p><strong>Methods: </strong>This cross-sectional study was conducted from March to September 2022. Adult epilepsy patients were recruited from a neurology outpatient clinic. Information on current and past ASM use was obtained from electronic medical records and patient interviews. ASMs were categorized into 4 groups: enzyme-inhibiting ASM (Valproate), enzyme-inducing ASMs (EIASMs), weak EIASMs, and non-EIASMs. Sarcopenia was defined using standard criteria based on muscle mass, strength, and physical performance. Statistical analyses included descriptive statistics and logistic regression using IBM SPSS Statistics Version 26.0.</p><p><strong>Results: </strong>A total of 200 patients were included. Univariate analysis showed significant differences in current EIASM use, duration of EIASM use, and phenytoin use between sarcopenia and non-sarcopenia groups (P = 0.030, P = 0.029, and P = 0.045, respectively). Logistic regression identified age (P = 0.030; OR = 1.045), body mass index (P = 0.001; OR = 0.672), and EIASM use (P = 0.023; OR = 5.091) as independent factors associated with sarcopenia.</p><p><strong>Conclusion: </strong>Enzyme-inducing ASMs, particularly phenytoin, are associated with sarcopenia diagnosis in epilepsy patients. Older age and lower BMI were also associated with sarcopenia. Individualized ASM selection and early screening are recommended.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145243821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empagliflozin Reduces Risk of Hospitalization in Patients With Chronic Kidney Disease in the EMPA-KIDNEY Trial.","authors":"Anastasia Uster, Nihar Desai, Sankar D Navaneethan, Egon Pfarr, Anna Rita Mazo","doi":"10.1016/j.clinthera.2025.09.005","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.005","url":null,"abstract":"<p><strong>Purpose: </strong>Chronic kidney disease (CKD) increases hospitalization risk. In the randomized, phase III, EMPA-KIDNEY trial, empagliflozin significantly reduced risk of all-cause hospitalizations (ACH; first and recurrent) vs placebo. This post hoc analysis of the EMPA-KIDNEY trial examines the burden of ACH in CKD and the effects of empagliflozin on ACH.</p><p><strong>Methods: </strong>Participants with CKD (n = 6609) were randomized to empagliflozin 10 mg or placebo. Reasons for hospitalizations were derived from adverse events leading to hospitalization, assessed by system organ class.</p><p><strong>Findings: </strong>Overall, 1995 participants (1035 placebo, 960 empagliflozin) had ≥1 ACH (1895 ACH in placebo and 1611 in the empagliflozin 10-mg groups). The estimated mortality rate after first hospitalization in participants with ≥1 hospitalization was 12% after 1 year and 18% after 2 years, and risk of death was ∼10 times higher vs those without (hazard ratio [HR] 9.53; 95% confidence interval [CI], 7.18-12.64; P < 0.0001). The most common reasons for hospitalization were infections and infestations, surgical and medical procedures, investigations, cardiac disorders, renal and urinary disorders, and metabolic disorders. Risk of ACH was significantly reduced for empagliflozin vs placebo (HR: 0.86, 95% CI, 0.78-0.95, P = 0.003). This was consistent regardless of baseline diabetes status, estimated glomerular filtration rate, or urinary albumin-to-creatinine ratio. Mean cumulative incidence of ACH in empagliflozin and placebo groups diverged shortly after randomization and separated further over time. Risk of hospital admissions from cardiovascular (CV), renal, or metabolic conditions was significantly lower with empagliflozin vs placebo (P < 0.05).</p><p><strong>Implications: </strong>Treatment with empagliflozin significantly reduced risk of ACH, including those attributed to CV, renal, or metabolic conditions.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov number: </strong>NCT03594110.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor Regarding “Treatment Persistence Among Anti–Tumor Necrosis Factor–experienced Patients With Ulcerative Colitis Switching to a Biologic With a Different Mode of Action or Cycling to Another Anti–Tumor Necrosis Factor Agent”","authors":"Joaquín Borrás-Blasco PhD ,&nbsp;Alejandro Valcuende-Rosique PhD ,&nbsp;Silvia Cornejo-Uixeda PharmD","doi":"10.1016/j.clinthera.2025.06.009","DOIUrl":"10.1016/j.clinthera.2025.06.009","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 950-951"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145236492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety Profiles of Trofinetide in Pediatric Rett Syndrome Population: A Real-World Postmarketing Pharmacovigilance Analysis","authors":"Jingjing Li MD ,&nbsp;Zhiyue Zhang MD ,&nbsp;Tao Yan PhD","doi":"10.1016/j.clinthera.2025.07.022","DOIUrl":"10.1016/j.clinthera.2025.07.022","url":null,"abstract":"<div><h3>Purpose</h3><div>Trofinetide, a synthetic analog of glycine-proline-glutamate, is the only approved therapy for Rett syndrome. This study evaluated the safety profile of trofinetide in pediatric patients with Rett syndrome using real-world pharmacovigilance data.</div></div><div><h3>Methods</h3><div>Adverse event (AE) reports were extracted from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) from Q1 2023 to Q4 2024. Disproportionality analyses were conducted using ROR, PRR, BCPNN, and MGPS to detect AE signals associated with trofinetide use in individuals under 18 years. A Weibull distribution model was applied to assess time-to-onset patterns. Subgroup analyses by age and dose, as well as sensitivity analyses excluding common co-medications, were conducted to evaluate signal consistency.</div></div><div><h3>Findings</h3><div>Most patients were female (95.4%), and all reports originated from the United States. Common labeled AEs were confirmed, including diarrhoea (<em>n</em> = 1,528; ROR = 38.1), vomiting (<em>n</em> = 434; ROR = 5.96), and seizures (<em>n</em> = 251; ROR = 5.30). Off-label signals included weight decreased (<em>n</em> = 135; ROR = 7.21), tremor (<em>n</em> = 39; ROR = 3.37), dystonia (<em>n</em> = 18; ROR = 4.39), and dyskinesia (<em>n</em> = 24; ROR = 4.53). Over 70% of AEs occurred within the first month. Hypersomnia was more frequently reported in younger children (ROR = 12.11), and higher doses were associated with psychiatric symptoms. Subgroup and sensitivity analyses confirmed the robustness of key signals.</div></div><div><h3>Implications</h3><div>This study provides critical real-world safety data on trofinetide use in pediatric Rett syndrome, identifying both expected and emerging AEs. Findings highlight the importance of monitoring dose-related and age-specific adverse events in clinical settings.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 859-866"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of Olpasiran in Chinese Participants With Elevated Serum Lipoprotein(a)","authors":"Winnie Sohn PhD ,&nbsp;Kathryn C.B. Tan MBBCH, MD, FRCP, FHKCP, FHKAM ,&nbsp;Trupti Shah MD MPH ,&nbsp;Yinhao Du PhD ,&nbsp;Jingying Wang PhD ,&nbsp;Shuo Zhang PhD ,&nbsp;Stephen Flach MD ,&nbsp;Jessica Ward PhD","doi":"10.1016/j.clinthera.2025.07.021","DOIUrl":"10.1016/j.clinthera.2025.07.021","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Cardiovascular disease (CVD) remains a major cause of premature mortality and disability worldwide, with China ranking among the highest in CVD deaths. Lipoprotein(a) (Lp(a)) is a circulating lipoprotein particle that, when elevated, may increase CVD risk. Reduced Lp(a) levels with existing cardiovascular treatments are modest, and evidence confirming whether lowering Lp(a) leads to cardiovascular benefit is lacking. Olpasiran (AMG 890), a liver cell-targeting small interfering RNA, has been shown to elicit profound Lp(a) reductions with an acceptable safety profile and is being evaluated in clinical trials worldwide. Therefore, investigating olpasiran’s treatment potential for cardiovascular risk reduction in the Chinese population is important.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Participants and Methods&lt;/h3&gt;&lt;div&gt;This is a phase 1, open-label, randomized, single-dose, parallel-group study in Chinese participants with elevated serum Lp(a). Participants with serum Lp(a) concentrations ≥70 nmol/L (or approximately ≥27 mg/dL) were randomized 1:1 to receive a single subcutaneous dose of olpasiran (75 or 225 mg). Olpasiran pharmacokinetic (PK) results were the primary endpoints; treatment-emergent adverse events (TEAEs), clinical laboratory tests, 12-lead electrocardiograms (ECGs), vital signs, lipids, and serum Lp(a) concentrations were the secondary endpoints.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Twenty-four participants (12 per dose group) were randomized, and 23 participants completed the study. After reaching maximal serum concentrations (75 mg: 167 ng/mL; 225 mg: 667 ng/mL) in ∼3 hours, olpasiran concentrations in both groups declined rapidly and were predominantly cleared from circulation within 3 days. Sustained reductions in Lp(a) concentrations from baseline were observed for both doses, with maximal reductions seen on day 57 (75 mg: –94.8%; 225 mg: –99.2%). All TEAEs associated with olpasiran were mild/moderate in severity, with four participants in the 225 mg dose group experiencing five mild TEAEs at the injection site. No notable treatment- or dose-related trends in clinical laboratory evaluations, vital signs, ECGs, physical examinations, or lipid panel results were identified, and no TEAEs leading to discontinuation or deaths were reported.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion&lt;/h3&gt;&lt;div&gt;Results from this study, as well as previous studies, indicate that olpasiran effectively and safely reduces Lp(a) levels in a similar manner across different ethnic populations.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;Olpasiran administration (75 and 225 mg) was safe and well-tolerated in Chinese participants, and olpasiran PK and Lp(a) responses are generally consistent with those observed in East Asian/non–East Asian participants. Dose adjustments of olpasiran based on ethnicity are therefore not warranted, and work investigating the effects of olpasiran treatment on long-term cardiovascular risk in East Asian populations should continue.&lt;/","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 851-858"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Semaglutide 2.4 mg on Healthcare Resource Utilization and Medical Costs in Patients With Heart Failure in the United States (SHINE-HF)","authors":"Wojciech Michalak MSc ,&nbsp;Zhenxiang Zhao ,&nbsp;Mads Faurby ,&nbsp;Sara Alvarez ,&nbsp;Angela Fitch","doi":"10.1016/j.clinthera.2025.07.018","DOIUrl":"10.1016/j.clinthera.2025.07.018","url":null,"abstract":"<div><h3>Purpose</h3><div>Obesity is a risk factor for premature development of heart failure (HF), one of the costliest obesity-related disorders. Clinical trials have demonstrated the efficacy of semaglutide 2.4 mg in improving outcomes in patients with HF. The study objective is to compare total all-cause medical costs and healthcare resource utilization (HCRU) among patients with overweight or obesity and HF treated with semaglutide 2.4 mg versus those not treated.</div></div><div><h3>Methods</h3><div>This retrospective, noninterventional, cohort study using the Komodo Healthcare Map© included patients with ≥1 inpatient or outpatient claim for HF during the baseline period, with overweight or obesity, and ≥12 months of continuous medical and pharmacy enrollment prior to and after the index date. Patients were included in the treated group if they first filled a prescription for semaglutide 2.4 mg between June 4, 2021-September 30, 2023. Semaglutide-untreated controls were randomly selected and propensity score matched to treated patients based on baseline demographics, clinical characteristics, medical costs, and HCRU. Medical costs and HCRU rates were compared using generalized linear models with a quasi-Poisson distribution.</div></div><div><h3>Findings</h3><div>In the year following treatment initiation with semaglutide 2.4 mg, mean all-cause medical costs were 28% lower (–$8,544) compared with patients not treated with semaglutide 2.4 mg ($19,094 vs $27,638 per patient per year [PPPY]; adjusted cost ratio [aCR] = 0.72, 95% confidence interval [CI] 0.60–0.84]; <em>P</em> &lt; 0.001). Inpatient costs with semaglutide 2.4 mg were 55% lower (–$6,304) than controls ($4,377 vs $10,681; aCR = 0.45 [95% CI 0.26–0.64]; <em>P</em> &lt; 0.001) and the inpatient visit rate PPPY was 42% lower in treated patients versus controls (0.15 vs. 0.26; adjusted inpatient visit rate ratio = 0.58 [95% CI 0.38–0.78]; <em>P</em> &lt; 0.001). The mean outpatient visit rate was higher in the semaglutide 2.4 mg-treated group (36.6 vs. 31.6; <em>P</em> = 0.027), but outpatient costs were slightly lower ($13,366 vs. $15,654; aCR = 0.88; 95% CI 0.74–1.03; <em>P</em> = 0.11) with semaglutide 2.4 mg, indicating more frequent outpatient services, but at a lower intensity level. No difference was found in emergency department costs or visit rates.</div></div><div><h3>Implications</h3><div>This real-world analysis of a large, US administrative claims database shows significantly lower medical costs and inpatient resource utilization among patients treated with semaglutide 2.4 mg with overweight or obesity and HF compared with those who did not receive semaglutide 2.4 mg. Improving outcomes with semaglutide 2.4 mg in these patients combined with lower costs and HCRU can help to manage the growing burden of HF to the US.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 875-883"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Epigallocatechin Gallate on Glycemic Index: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","authors":"Mohamed J. Saadh PhD ,&nbsp;Ibrahim Saeed Gataa PhD ,&nbsp;A.S. Hussam PhD ,&nbsp;Irwanjot Kaur PhD ,&nbsp;Abhishek Kumar PhD ,&nbsp;Pragati Godara PhD ,&nbsp;Rahadian Zainul PhD ,&nbsp;Khursheed Muzammil PhD ,&nbsp;Yousef Zahrani PhD","doi":"10.1016/j.clinthera.2025.07.015","DOIUrl":"10.1016/j.clinthera.2025.07.015","url":null,"abstract":"<div><h3>Purpose</h3><div>Epigallocatechin gallate (EGCG), a major catechin found in green tea, has been suggested to influence glycemic control. This systematic review and meta-analysis aim to evaluate the effects of EGCG on the glycemic index (GI) and related glycemic parameters.</div></div><div><h3>Methods</h3><div>Using predefined keywords, online databases (PubMed, Scopus, Web of Science Core Collection, and Google Scholar) were searched for relevant studies, published from inception up to May 2024. Initially 1994 studies were obtained out of which 41 RCTs were decided to be included for further analyses.</div></div><div><h3>Findings</h3><div>The meta-analysis demonstrated that EGCG supplementation led to statistically significant, but modest, reductions in fasting blood glucose (FBG), HbA1c, and HOMA-IR. Notably, the reduction in HbA1c (WMD: −0.18%, 95% CI: −0.35, −0.02; <em>P</em> = 0.029) was small and may not equate to clinically meaningful benefits for all populations. Furthermore, the effect on fasting insulin was not statistically significant (WMD: −0.50; 95% CI: −1.46, 0.47; <em>P</em> = 0.313), indicating a lack of robust or consistent impact on this parameter across studies.</div></div><div><h3>Implications</h3><div>Although EGCG supplementation is associated with improvements in some glycemic parameters, these effects especially for HbA1c and fasting insulin are modest and may not be clinically meaningful for most population. Therefore, current evidence does not strongly support the use of EGCG as a stand-alone intervention for glycemic control.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 925-934"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Randomized, Double-Blind, Placebo-Controlled Phase II Trial of AYP-101 (Soybean Phosphatidylcholine) for Submental Fat Reduction in Asian Adults","authors":"Sun Young Choi MD, PhD ,&nbsp;A.M. Abd El-Aty ,&nbsp;Beom Joon Kim MD, PhD","doi":"10.1016/j.clinthera.2025.07.016","DOIUrl":"10.1016/j.clinthera.2025.07.016","url":null,"abstract":"<div><h3>Purpose</h3><div>Submental fat (SMF) accumulation can affect self-image and psychological well-being, leading to a demand for nonsurgical treatment. AYP-101, which contains soybean phosphatidylcholine (SPC), is under investigation for SMF reduction. This study aimed to compare 2 concentrations of AYP-101 to placebo injections to determine the optimal concentration and evaluate safety and efficacy in reducing moderate to severe SMF in an Asian population.</div></div><div><h3>Methods</h3><div>This single-center, randomized, double-blind, placebo-controlled phase II trial enrolled 96 participants with moderate to severe SMF. Participants were randomly assigned to receive either a placebo or AYP-101 at either a low concentration (25 mg/mL) or a high concentration (50 mg/mL), administered every 2 weeks for up to 6 sessions. The primary endpoint was the proportion of participants achieving at least a 1-grade improvement in both the Evaluator-Reported Submental Fat Rating Scale (ER-SMFRS) and the Subject-Reported Submental Fat Rating Scale (SR-SMFRS) at 4 and 12 weeks after the final injection.</div></div><div><h3>Findings</h3><div>At 4 weeks post-treatment, 69.70% of the low-concentration group and 48.39% of the high-concentration group exhibited improvement in the ER-SMFRS, compared to 22.58% in the placebo group. Significant differences were noted between the low-concentration and placebo groups (<em>P</em> = 0.0002), with similar results at 12 weeks.</div></div><div><h3>Implications</h3><div>AYP-101, administered biweekly at a concentration of 25 mg/mL, appears to be a safe and effective nonsurgical option for reducing SMF in Asians.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 889-893"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers: A Concept in Reach of Maturity","authors":"Paul Beninger MD, MBA","doi":"10.1016/j.clinthera.2025.08.016","DOIUrl":"10.1016/j.clinthera.2025.08.016","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 827-829"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Drugs Associated With Tumor Lysis Syndrome: Insights From the US Food and Drug Administration Adverse Event Reporting System","authors":"Wei Wang MD ,&nbsp;Zirui Dong MD ,&nbsp;Qi Miao MD ,&nbsp;Baoan Hong MD ,&nbsp;Yuxuan Bo MD ,&nbsp;Xuezhou Zhang MD ,&nbsp;Xin Guan MD ,&nbsp;Ning Zhang MD","doi":"10.1016/j.clinthera.2025.08.001","DOIUrl":"10.1016/j.clinthera.2025.08.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency caused by rapid tumor cell breakdown, either spontaneously or after therapy, leading to electrolyte imbalances that can result in acute kidney injury, arrhythmias, seizures, and multiorgan failure. Despite its clinical importance, the relationship between anticancer drugs and TLS, particularly newer targeted therapies, remains poorly understood.</div></div><div><h3>Methods</h3><div>We analyzed the US Food and Drug Administration (FDA) Adverse Events Reporting System database, a repository of adverse events associated with medical products, to identify TLS cases reported from the first quarter of 2004 to the third quarter of 2024. For signal detection, we used disproportionality analysis with 4 algorithms—reported odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. These algorithms assessed statistical correlations between anticancer drugs and TLS, based on a 2 × 2 contingency table framework.</div></div><div><h3>Findings</h3><div>From the first quarter of 2004 to the third quarter of 2024, a total of 7340 TLS cases were documented in the FDA Adverse Events Reporting System database. Clinical characteristics, including age, sex, and outcomes, were analyzed. Among all reported TLS cases, 53.0% were men, and the mean age across all individuals was 56.9 ± 21.5 years. The incidence of TLS peaked in 2022, with a 42% increase from 2016 to 2017. A total of 118 antineoplastic drugs were identified as highly associated with TLS, of which only 18 had FDA-labeled TLS-related adverse reactions. Chemotherapy drugs were the most frequently associated with TLS. Venetoclax emerged as the top drug associated with TLS, comprising 10.72% of all TLS reports.</div></div><div><h3>Implications</h3><div>Our findings highlight critical drug-induced TLS associations, particularly with emerging targeted therapies such as venetoclax. The study underscores the need for clinicians to monitor TLS closely in patients receiving certain anticancer treatments and to refine therapeutic strategies to mitigate TLS risk, ensuring safer cancer care outcomes. Further longitudinal studies are warranted to validate these findings and enhance pharmacovigilance efforts.</div></div>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":"47 10","pages":"Pages 844-850"},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}