Expert Review of Clinical Pharmacology最新文献_第3页

From molecules to meaning: unpacking the antidepressant mechanisms of psychedelic drugs. 从分子到意义：揭秘迷幻药的抗抑郁机制。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-05-01 Epub Date: 2025-06-11 DOI: 10.1080/17512433.2025.2515866

Victor Pablo Acero, Taylor A Flatt, Peter M Gooch, Skylar J Gaughan, Adam W Levin, Alan K Davis

{"title":"From molecules to meaning: unpacking the antidepressant mechanisms of psychedelic drugs.","authors":"Victor Pablo Acero, Taylor A Flatt, Peter M Gooch, Skylar J Gaughan, Adam W Levin, Alan K Davis","doi":"10.1080/17512433.2025.2515866","DOIUrl":"10.1080/17512433.2025.2515866","url":null,"abstract":"Introduction: Psychedelic compounds are emerging treatments for depression, capable of producing rapid and lasting symptom reduction after 1-2 administrations in the context of psychotherapy - a stark contrast to traditional antidepressants. Despite promising outcomes, the mechanisms underlying psychedelics' reported antidepressant effects remain poorly understood and are often framed in fragmented ways. Clarifying these mechanisms is crucial for guiding future research and clinical innovation with psychedelics.Areas covered: This review critically examines current evidence on the mechanisms by which psychedelics may exert antidepressant effects. We highlight key mechanisms of action within biological, psychological, social, and spiritual domains that we believe are among the most compelling and deserving of further investigation. Throughout, we compare these mechanisms to those proposed for traditional antidepressants, identifying points of overlap and divergence.Expert opinion: Although mechanistic research is valuable, an overemphasis on identifying discrete pathways may limit psychedelic science. Psychedelics likely work through complex, interwoven biological, psychological, and experiential processes that cannot be fully reduced to single mechanisms. Future research should move beyond frameworks and metrics used to validate conventional antidepressants to explore how suprapharmacological factors - set, setting, therapy modality, and integration - shape outcomes. Embracing this complexity is essential to realizing psychedelics' full therapeutic potential for depression.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"263-280"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224876","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}

引用次数: 0

Physiologically-based pharmacokinetic modeling to predict the exposure and provide dosage regimens of adalimumab in patients with juvenile idiopathic arthritis. 基于生理的药代动力学模型预测阿达木单抗在幼年特发性关节炎患者中的暴露并提供剂量方案。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-05-01 Epub Date: 2025-05-12 DOI: 10.1080/17512433.2025.2502366

Ya-Xin Liu, Li-Ying Gong, Jin-Long Liu, Qi Pei, Yun Kuang, Guo-Ping Yang

{"title":"Physiologically-based pharmacokinetic modeling to predict the exposure and provide dosage regimens of adalimumab in patients with juvenile idiopathic arthritis.","authors":"Ya-Xin Liu, Li-Ying Gong, Jin-Long Liu, Qi Pei, Yun Kuang, Guo-Ping Yang","doi":"10.1080/17512433.2025.2502366","DOIUrl":"10.1080/17512433.2025.2502366","url":null,"abstract":"Background: Adalimumab has been approved for treating juvenile idiopathic arthritis (JIA). This study aimed to develop a physiologically-based pharmacokinetic (PBPK) model for adalimumab in JIA patients to optimize personalized treatment.Methods: A comprehensive literature search identified 13 clinical studies as the dataset for constructing and validating a PBPK model of adalimumab. Initially, a PBPK model for adalimumab in adults was constructed using PK-Sim and Mobi software. Subsequently, virtual pediatric populations were created by incorporating age-dependent parameters from the PK-Sim database, extending the model to JIA patients. Finally, based on the developed PBPK model for adalimumab in JIA patients, dosing regimens were evaluated for different age groups.Results: This study successfully developed and validated a PBPK model for adalimumab in both adult and pediatric populations. The model for adults accurately predicted 92.90% of the concentrations within 0.5-2 times the observed values, while the pediatric model predicted 90.62% of the concentrations within 0.5-2-fold range. For pediatric patients with JIA, age- and weight-based dosing is recommended to achieve trough concentrations comparable to those in adults.Conclusion: A PBPK model for adalimumab in pediatric patients with JIA was developed, providing a basis for personalized dosing regimens in this population.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"305-312"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965037","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}

引用次数: 0

Effects of the augmentation with quetiapine or olanzapine on the metabolism of duloxetine: a retrospective analysis. 喹硫平或奥氮平对度洛西汀代谢的影响：回顾性分析。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-05-01 Epub Date: 2025-04-04 DOI: 10.1080/17512433.2025.2486998

Nele Römer, Arnim Johannes Gaebler, Irene Neuner, Ekkehard Haen, Christoph Hiemke, Georgios Schoretsanitis, Michael Paulzen

{"title":"Effects of the augmentation with quetiapine or olanzapine on the metabolism of duloxetine: a retrospective analysis.","authors":"Nele Römer, Arnim Johannes Gaebler, Irene Neuner, Ekkehard Haen, Christoph Hiemke, Georgios Schoretsanitis, Michael Paulzen","doi":"10.1080/17512433.2025.2486998","DOIUrl":"10.1080/17512433.2025.2486998","url":null,"abstract":"Background: In antidepressant augmentation strategies, olanzapine or quetiapine are often concomitantly administered to duloxetine. The use of the same enzymes for the degradation of the drugs may lead to clinically relevant drug-drug-interactions, DDIs. So far, DDIs between olanzapine or quetiapine and duloxetine have only been studied in rats or in small numbers of patients.Methods: Out of a large therapeutic drug monitoring (TDM) database of duloxetine concentrations, three matched study groups were considered to investigate potential DDIs: a group of patients co-medicated with olanzapine (n = 81), a group co-medicated with quetiapine (n = 105) and a control group receiving only duloxetine (n = 105).Results: Neither in the olanzapine group, nor in the quetiapine group, duloxetine plasma concentrations or dose-adjusted plasma concentrations differed significantly from the control group (p = 0.6759; p = 0.5841). The proportion of patients within the so-called therapeutic reference range was similar in all three groups (p = 0.635). However, smokers showed by 30% lower duloxetine plasma concentrations (p = 0.0179) and 32.5% lower dose-adjusted concentrations (p = 0.0003) compared to nonsmokers.Conclusion: Our findings indicate that the combination of duloxetine and olanzapine or quetiapine is - from a pharmacokinetic view - a safe treatment option. TDM should be applied in case of co-medications to enhance therapeutic effectiveness and patients' safety.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"297-303"},"PeriodicalIF":3.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751822","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}

引用次数: 0

Impact of COVID-19 pandemic on the prescribing pattern of oral anticoagulants in the English primary care setting: a population-based segmented interrupted time series analysis of over 53 million individuals. COVID-19大流行对英国初级保健机构口服抗凝剂处方模式的影响：对5300多万人进行的基于人群的分段中断时间序列分析

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI: 10.1080/17512433.2025.2473613

Amanj Kurdi, Abdulaziz Albutti, Omeed Darweesh, Karwan M Amen, Kirmanj Baker, Hardee Karwi, Brian Godman

{"title":"Impact of COVID-19 pandemic on the prescribing pattern of oral anticoagulants in the English primary care setting: a population-based segmented interrupted time series analysis of over 53 million individuals.","authors":"Amanj Kurdi, Abdulaziz Albutti, Omeed Darweesh, Karwan M Amen, Kirmanj Baker, Hardee Karwi, Brian Godman","doi":"10.1080/17512433.2025.2473613","DOIUrl":"10.1080/17512433.2025.2473613","url":null,"abstract":"Background: The COVID-19 pandemic disrupted healthcare delivery, impacting oral anticoagulants (OAC) prescribing due to increased thromboembolic risks, Vaccine-induced immune thrombotic thrombocytopenia, and guidelines favoring Direct Oral Anticoagulants (DOACs) over warfarin. Previous studies were limited to short-term analyses.Research design and methods: A segmented interrupted time series analysis was conducted using the English primary care Prescription Cost Analysis data from March/2018-March/2024 to assess the impact of the first and second COVID-19 lockdowns in March and November 2020, respectively. Trends in OAC utilisation were measured using number of items per 1,000 inhabitants (NIT) and defined daily dose per 1,000 inhabitants per day (DTD).Results: Overall, oral anticoagulants prescribing increased significantly. Pre-pandemic, both NIT (β1: 0.09; 95%CI: 0.02, 0.16) and DTD (β1:0.13; 95%CI: 0.09, 0.16) showed positive trends. Post-first lockdown, DTD slope declined significantly (β3:-0.22; 95%CI: -0.42, -0.03). Post-second lockdown, DTD rose in both immediate level (β4:1.39; 95%CI: 0.34, 2.45) and slope (β5: 0.20; 95%CI: 0.0015, 0.39). Warfarin usage declined initially but rebounded, while DOACs, particularly apixaban, increased substantially (β4:0.96; 95%CI: 0.11, 1.81).Conclusions: The COVID-19 pandemic significantly impacted oral anticoagulant prescribing patterns in England. While DOAC utilisation continued to rise, warfarin use declined significantly post-first lockdown but rebounded after the second lockdown.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"237-246"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143531576","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}

引用次数: 0

Scoping review of the availability and uptake of disease modifying therapies in children and adolescents with multiple sclerosis. 儿童和青少年多发性硬化症疾病修饰疗法的可用性和吸收的范围综述。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1080/17512433.2025.2481868

Lauren Strasser, Beyza Ciftci, Joley Johnstone, Jessie Cunningham, Helen Tremlett, E Ann Yeh

{"title":"Scoping review of the availability and uptake of disease modifying therapies in children and adolescents with multiple sclerosis.","authors":"Lauren Strasser, Beyza Ciftci, Joley Johnstone, Jessie Cunningham, Helen Tremlett, E Ann Yeh","doi":"10.1080/17512433.2025.2481868","DOIUrl":"10.1080/17512433.2025.2481868","url":null,"abstract":"Introduction: Approximately 10% of individuals with multiple sclerosis (MS) have pediatric-onset (<18-years-old). Pediatric-specific barriers to accessing disease modifying therapies (DMT) exist. Issues include few pediatric-based randomized controlled trials (RCT), often required for formal regulatory approval, and resultant challenges with cost/coverage. This review assessed real-world DMT uptake in pediatric-MS to better understand potential barriers.Areas covered: We performed a scoping review of observational studies examining DMTs in patients with pediatric-MS published between 07/1993 and 06/2024. PRISMA guidelines were used. Databases searched included: Cochrane Library, Ovid MEDLINE/Embase, Scopus, and Web of Science. Studies must include >10 DMT exposed pediatric-MS patients with full-text available in English. RCTs/pharmaceutical-industry funded studies were excluded. Of 2114 abstracts screened, 88 studies were included. A total of 21,591 patients (13,411 females) were included. DMTs were used in 68.7% (n = 14,833). Most studies were from Europe (53.4%), North America (22.7%), or the Middle East (10%). Regional variabilities were found in DMT uptake between continents. Only 13 (14.8%) studies included information on DMT funding source.Expert opinion: Pediatric-MS patients showed low DMT uptake with variability in DMT use based on region. Limited data was found regarding specific barriers to DMT access. Further research is needed to better understand regional barriers to access.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"197-210"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656412","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}

引用次数: 0

Can we optimize the use of renin-angiotensin-system inhibitors in patients with chronic kidney disease? 我们能否优化肾素-血管紧张素系统抑制剂在慢性肾病患者中的应用？

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-19 DOI: 10.1080/17512433.2025.2468954

Panagiotis I Georgianos, Christodoula Kourtidou, Konstantinos Leivaditis, Anastasios Kollias, Vassilios Liakopoulos

引用次数: 0

Efficacy and safety of dupilumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis. dupilumab治疗慢性鼻窦炎伴鼻息肉的疗效和安全性：一项系统综述和荟萃分析。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-02-22 DOI: 10.1080/17512433.2025.2468970

Linger Sim, Norasnieda Md Shukri, Najib Majdi Yaacob, Chenthilnathan Periasamy, Musat Gabriela Cornelia, Baharudin Abdullah

{"title":"Efficacy and safety of dupilumab in chronic rhinosinusitis with nasal polyps: a systematic review and meta-analysis.","authors":"Linger Sim, Norasnieda Md Shukri, Najib Majdi Yaacob, Chenthilnathan Periasamy, Musat Gabriela Cornelia, Baharudin Abdullah","doi":"10.1080/17512433.2025.2468970","DOIUrl":"10.1080/17512433.2025.2468970","url":null,"abstract":"Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) primarily displays type 2 inflammation, characterized by the activation of interleukin (IL)-4, IL-5, and IL-13 in the pathway. The purpose of this study is to determine the efficacy and safety of dupilumab (an IL-4 antagonist) in treating CRSwNP.Methods: A detailed search was performed in PubMed, Embase and the Cochrane Library databases. All published English-language randomized controlled trials (RCTs) that employed dupilumab to treat CRSwNP in adult patients (≥18 years old) were considered.Results: Three RCTs and 25 studies with 784 individuals were included. The use of dupilumab revealed improvement in polyp size (MD -1.80; 95% CI -2.25 to -1.36), Lund-Mackay score (MD -7.01, 95% CI -9.64 to -4.38), congestion (MD -0.86, 95% CI -0.99 to -0.73), smell (MD 10.83, 95% CI 9.59 to 12.08) and health-related quality of life (MD -19.61, 95% CI -22.53 to -16.69). Systemic corticosteroid use (RR 0.28, 95% CI 0.20-0.39) and revision surgery (RR 0.17, 95% CI 0.05-0.52) were reduced. Serious adverse events were reduced in dupilumab group (RR 0.47; 95% CI 0.29 to 0.76) with no change in risk of adverse events (RR 0.98, 95% CI 0.87 to 1.11).Conclusions: Dupilumab is effective with minimal adverse events.Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42023413004.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"211-224"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440131","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}

引用次数: 0

Complications related to oral corticosteroid use in asthma patients: a retrospective cohort study. 哮喘患者口服皮质类固醇相关并发症：一项回顾性队列研究

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1080/17512433.2025.2470834

Chih-Cheng Lai, Chao-Hsien Chen, Ya-Hui Wang, Cheng-Yi Wang, Hao-Chien Wang

{"title":"Complications related to oral corticosteroid use in asthma patients: a retrospective cohort study.","authors":"Chih-Cheng Lai, Chao-Hsien Chen, Ya-Hui Wang, Cheng-Yi Wang, Hao-Chien Wang","doi":"10.1080/17512433.2025.2470834","DOIUrl":"10.1080/17512433.2025.2470834","url":null,"abstract":"Background: Asthma patients requiring oral corticosteroids (OCS) are at increased risk of adverse effects. Research focusing on asthma patients adhering to guideline-directed therapy remains limited. This study evaluates the adverse effects of corticosteroids in asthma patients treated with high-dose inhaled corticosteroids (ICS) who required additional OCS due to inadequate disease control.Research design and methods: We conducted a retrospective cohort study of asthma patients from Taiwan's asthma pay-for-performance program, who had used high-dose ICS for at least 90 days, categorizing them based on OCS use. In the short-term period (3 months), patients were classified into a control group (no OCS) and an OCS group (≥450 mg OCS within 90 days). In the long-term period (6 months), the OCS group consisted of patients receiving ≥ 900 mg OCS within 180 days.Results: A total of 173,835 patients were enrolled for analysis. We assessed the risks of osteoporosis, diabetes, hypertension, infections, cardiovascular diseases, mental health disorders, and ocular conditions. Both short- and long-term OCS users exhibited significantly higher risks of these adverse outcomes compared to the control group.Conclusions: These findings highlight the substantial health risks associated with OCS. Clinicians should carefully consider alternative strategies to minimize harm while ensuring effective disease control.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"225-236"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500101","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}

引用次数: 0

Nicotine e-cigarettes for smoking cessation: a clinical pharmacology perspective. 尼古丁电子烟戒烟：临床药理学的观点。

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-04-01 Epub Date: 2025-03-07 DOI: 10.1080/17512433.2025.2472837

Victoria Ameral, Mehmet Sofuoglu, Megan M Kelly

{"title":"Nicotine e-cigarettes for smoking cessation: a clinical pharmacology perspective.","authors":"Victoria Ameral, Mehmet Sofuoglu, Megan M Kelly","doi":"10.1080/17512433.2025.2472837","DOIUrl":"10.1080/17512433.2025.2472837","url":null,"abstract":"Introduction: Smoking cessation improves quality of life and increases life expectancy by up to a decade. Though two-thirds of people who smoke report a desire to quit, less than a quarter plan to quit within the coming month. The relative risks and benefits of e-cigarettes, proposed as a novel tool to support smoking cessation, are critical to monitor as the evidence evolves.Areas covered: This review summarizes the evidence for smoking cessation treatment, characteristics and pharmacology of e-cigarettes, support for e-cigarettes for smoking cessation, and relevant harm reduction principles. Populations at the highest risk for continued cigarette smoking (e.g. individuals with co-occurring substance use and mental health conditions) and those who are vulnerable to initiating nicotine use through access to e-cigarettes (e.g. adolescents), are also discussed.Expert opinion: Evidence indicating that e-cigarettes are comparable to nicotine replacement therapy points to their promise as a smoking cessation and harm reduction option for individuals who decline other treatment options. Future work should evaluate the comparative efficacy of e-cigarettes for historically excluded groups and the relative effects of specific products and monitor for any long-term effects. Evidence-based clinical guidelines are also needed to inform clinical practice in this rapidly evolving area.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"189-196"},"PeriodicalIF":3.6,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566544","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}

引用次数: 0

Effectiveness and safety of thiopurines in inflammatory bowel disease patients with NUDT15 polymorphism: a real-world retrospective study. 硫嘌呤治疗NUDT15多态性炎症性肠病患者的有效性和安全性：一项真实世界的回顾性研究

IF 3.6 3区医学

Expert Review of Clinical Pharmacology Pub Date : 2025-03-01 Epub Date: 2025-02-11 DOI: 10.1080/17512433.2025.2465425

Abhirup Chatterjee, Prateek Bhatia, Saroj K Sinha, Anupam K Singh, Harshal S Mandavdhare, Jimil Shah, Vaneet Jearth, Arpit Sasani, Aravind Sekar, Minu Singh, Usha Dutta, Vishal Sharma

{"title":"Effectiveness and safety of thiopurines in inflammatory bowel disease patients with NUDT15 polymorphism: a real-world retrospective study.","authors":"Abhirup Chatterjee, Prateek Bhatia, Saroj K Sinha, Anupam K Singh, Harshal S Mandavdhare, Jimil Shah, Vaneet Jearth, Arpit Sasani, Aravind Sekar, Minu Singh, Usha Dutta, Vishal Sharma","doi":"10.1080/17512433.2025.2465425","DOIUrl":"10.1080/17512433.2025.2465425","url":null,"abstract":"Background: Thiopurine S-methyltransferase (TPMT) and Nudix hydrolase (NUDT15) polymorphisms predispose to thiopurine-related leukopenia.Methods: Retrospective evaluation of inflammatory bowel disease (IBD) patients harboring NUDT15 polymorphisms and exposed to thiopurines. We report the frequency of NUDT15 polymorphism, frequency of leukopenia, the tolerated dose of azathioprine, and the clinical efficacy of thiopurines.Results: Of 1440 patients, 118 (8.2%) had NUDT15 polymorphism. Among 51 with complete details, 46 were heterozygous (90.2%), and 5 homozygous (9.2%) for NUDT15. Twenty (43.5%) heterozygous and all homozygous patients developed leukopenia. Leukopenia was significantly more in NUDT15 heterozygous group compared to controls (43.45% vs 7.8%, Odds ratio: 9, 95% CI 3.57-22.9). The maximum tolerated dose of azathioprine was lower in NUDT15 heterozygous group (1.1 ± 0.4 mg per kg vs 1.7 ± 0.7 mg per kg, p = 0.002). The mean time to leukopenia was earlier in the heterozygous group vs controls (19 ± 56 weeks vs 70 ± 53 weeks, p-value 0.002). Seven (35%) of 20 heterozygous patients who developed leukopenia, could be maintained at a lower dose of thiopurine. Twenty-five maintained clinical remission while on thiopurines.Conclusion: Thiopurines should be avoided in NUDT15 homozygous but can be used cautiously at lower dosages with frequent monitoring among heterozygous patients.","PeriodicalId":12207,"journal":{"name":"Expert Review of Clinical Pharmacology","volume":" ","pages":"175-183"},"PeriodicalIF":3.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373966","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}

引用次数: 0