JAPhA Pharmacotherapy最新文献

Leveraging real-world data to create vancomycin population pharmacokinetic models in younger adults and patients with low serum creatinine 利用真实世界的数据在年轻成人和低血清肌酐患者中创建万古霉素人群药代动力学模型

JAPhA Pharmacotherapy

Pub Date : 2026-01-01 DOI: 10.1016/j.japhar.2025.100026

Jordan T. Brooks, Maria-Stephanie A. Hughes, Jonathan D. Faldasz, Ron J. Keizer, Jasmine H. Hughes

Background

Vancomycin population pharmacokinetic (popPK) models are essential for precision dosing but can perform poorly in underrepresented populations, including younger adults and patients with low serum creatinine (sCr). These 2 populations show altered pharmacokinetics (PK) compared with the general population; younger patients exhibit faster clearance (CL), whereas low sCr often reflects body composition rather than renal function, leading to implausible CL estimates.

Objectives

This study aimed to develop 2 vancomycin popPK models on large, real-world data sets and compare model predictive performance in historically underrepresented populations of individuals: young adults and individuals with low sCr.

Methods

Two new vancomycin popPK models were developed using retrospective InsightRX Nova platform data. The model for young adults was trained on patients aged 18-35 years (n = 6080), whereas the low sCr model included adults of all ages with sCr values of less than 0.8 mg/dL (n = 2354). Predictive performance was evaluated using mean percent error, normalized root mean square error (nRMSE), and accuracy (within 15% or 2.5 mg/dL of observed concentrations). Predictive performance was compared across 5 established models using both holdout internal validation data sets and a large, broad adult population external validation data set.

Results

Both models used 2-compartment structures with combined proportional and additive error. The young adult model incorporated fat-free mass (FFM) and estimated glomerular filtration rate via Chronic Kidney Disease Epidemiology Collaboration 2021, whereas the low sCr model used FFM, raw sCr, age, and sex. The young adult model showed superior accuracy and lower nRMSE across prediction types compared with established models in the internal validation data set. For modeling low sCr, application of rounding sCr rules did not improve model performance. External validation on 384,876 patients confirmed both models generalized well beyond their development populations, with the young adult model performing across age groups and the low sCr model maintaining performance for sCr of less than 1.0 mg/dL.

Conclusions

Developing population-specific vancomycin popPK models improves predictive performance for underrepresented groups. Using measured sCr without imposing clinically common sCr rounding rules optimizes performance. These findings support continued refinement of targeted PK models.

万古霉素群体药代动力学（popPK）模型对于精确给药至关重要，但在代表性不足的人群中表现不佳，包括年轻人和血清肌酐（sCr）低的患者。与普通人群相比，这两个群体的药代动力学（PK）发生了改变；年轻患者表现出更快的清除率（CL），而低sCr通常反映的是身体成分而不是肾功能，这导致对CL的估计不可信。本研究旨在在大型真实数据集上开发两种万古霉素popPK模型，并比较模型在历史上代表性不足的个体群体（年轻人和低sCr个体）中的预测性能。方法利用InsightRX Nova平台的回顾性数据，建立2个新的万古霉素popPK模型。青年人模型的训练对象是18-35岁的患者（n = 6080），而低sCr模型包括sCr值小于0.8 mg/dL的所有年龄段的成年人（n = 2354）。使用平均误差百分比、标准化均方根误差（nRMSE）和准确度（在观察浓度的15%或2.5 mg/dL范围内）评估预测性能。使用holdout内部验证数据集和大量广泛的成年人外部验证数据集，比较了5个已建立模型的预测性能。结果两种模型均采用比例误差和加性误差相结合的2室结构。年轻成人模型纳入无脂质量（FFM）和通过2021年慢性肾脏疾病流行病学合作组织估计的肾小球滤过率，而低sCr模型使用FFM、原始sCr、年龄和性别。在内部验证数据集中，与已建立的模型相比，青壮年模型在预测类型上具有更高的准确性和更低的nRMSE。对于低sCr的建模，四舍五入sCr规则的应用并没有提高模型的性能。对384,876名患者的外部验证证实，这两种模型的适用性远远超出了其发育人群，年轻成人模型在各个年龄组都有表现，低sCr模型在sCr低于1.0 mg/dL时保持表现。结论开发人群特异性万古霉素popPK模型可提高代表性不足群体的预测性能。使用测量的sCr，而不强加临床常见的sCr舍入规则，可优化性能。这些发现支持了靶向PK模型的持续改进。

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引用次数: 0

Medication adherence after transition to emicizumab in patients with severe hemophilia A: Results from the ADHEMI study 严重血友病A患者过渡到emicizumab后的药物依从性：来自ADHEMI研究的结果

JAPhA Pharmacotherapy

Pub Date : 2025-11-18 DOI: 10.1016/j.japhar.2025.100025

Laurie Pagnot, Teddy Novais, Véronique Cahoreau, Isabelle Lopez, Christelle Prudent, Marie Hamon, Estelle Leroy, Anne Cécile Gérout, Elise Toguyeni, Ludovic Sylvestre, Julien Jouglen, Rémi Varin, Valérie Chamouard

Background

Hemophilia A (HA) is a rare X-linked congenital bleeding disorder characterized by a deficiency in coagulation factor VIII (FVIII). Standard treatment includes regular intravenous (IV) injections of clotting factor concentrates, known as prophylaxis. Recent advances, such as subcutaneous nonfactor replacement therapy like emicizumab, have had an impact on management strategies for patients with HA, notably by reducing the burden of IV injections.

Objectives

This study aimed to assess the change in medication adherence after the HA treatment modality switch from FVIII or bypassing agents (BPAs) in the case of inhibitors to subcutaneous emicizumab for patients with severe HA.

Methods

A multicenter retrospective study was conducted across 11 French reference centers for hemophilia. The study included 187 patients with severe HA treated with emicizumab for at least 12 months after a minimum of 12 months with FVIII or BPA prophylaxis. Medication adherence was measured using the medication possession ratio (MPR), calculated for both periods, accounting or not for the inclusion of emergency doses (EDs). These doses were prescribed in addition to the prophylactic regimen in the case of hemorrhage.

Results

Medication adherence statistically significant increased after switching to emicizumab (mean ± SD) (MPR 0.99 ± 0.07) compared with the previous period with FVIII or BPAs (MPR 0.85 ± 0.23 without EDs, 0.91 ± 0.24 with EDs, P < 0.001). The proportion of adherent patients (MPR ≥ 90%) rose from 44.4% (without EDs) and 54.5% (with EDs) to 92.0% after the switch (P < 0.001).

Conclusions

Switching to emicizumab improves medication adherence in patients with hemophilia A.

血友病A （HA）是一种罕见的x连锁先天性出血性疾病，其特征是凝血因子VIII （FVIII）缺乏。标准治疗包括定期静脉注射凝血因子浓缩物，称为预防。最近的进展，如皮下非因子替代疗法，如emicizumab，已经对HA患者的管理策略产生了影响，特别是通过减少静脉注射的负担。本研究旨在评估严重HA患者的HA治疗方式从FVIII或旁路药物（BPAs）抑制剂切换到皮下emicizumab后药物依从性的变化。方法在法国11个血友病参考中心进行多中心回顾性研究。该研究包括187例严重HA患者，在接受FVIII或BPA预防治疗至少12个月后，接受emicizumab治疗至少12个月。使用药物占有比（MPR）测量药物依从性，计算两个时期，考虑或不考虑紧急剂量（EDs）。这些剂量是在出血情况下的预防方案之外规定的。结果切换到emicizumab后，与先前使用FVIII或bpa相比，药物依从性（平均±SD）（MPR 0.99±0.07）有统计学意义（MPR 0.85±0.23，无ed， 0.91±0.24,P < 0.001）。转换后的依从性患者（MPR≥90%）比例从44.4%（无ed）和54.5%（有ed）上升到92.0% （P < 0.001）。结论：改用艾美珠单抗可改善A型血友病患者的药物依从性。

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引用次数: 0

Adherence in initiators of combination therapy among drug-naïve patients with type 2 diabetes: A real-world study using group-based trajectory model drug-naïve 2型糖尿病患者联合治疗发起者的依从性：一项使用基于组的轨迹模型的现实世界研究

JAPhA Pharmacotherapy

Pub Date : 2025-11-10 DOI: 10.1016/j.japhar.2025.100024

Bilqees Fatima, Sai S. Cheruvu, Samuel C. Ofili, Zahra Majd, Susan Abughosh

Background

Recent clinical trial data suggested that early use of combination therapy among patients with diabetes has a more durable effect on glycemic control. However, the complexity of multidrug regimens associated with early use of combination therapy makes adherence more challenging, and combination therapy adherence is often inadequately captured.

Objectives

This study aimed to assess the adherence trajectories of initial combination therapy users during the first year of antidiabetic treatment initiation.

Methods

A retrospective study using Merative MarketScan research databases (2017-2019). Drug-naïve patients with type 2 diabetes (T2D) who received initial combination therapy and were continuously enrolled in commercial or Medicare insurance plans were identified. Patients who received 2 distinct antidiabetic medications within 30 days or on the same date were identified as initial combination therapy users. Adherence was measured within 1 year after the index date using the proportion of days covered. Group-based trajectory model (GBTM) was used to identify distinct longitudinal adherence patterns of combination therapy users. A multinomial regression model was performed to examine predictors associated with nonadherence trajectories.

Results

A total of 116,597 drug-naïve patients with T2D were identified, of whom 14,118 (12.1%) initiated combination therapy. GBTM with 4 distinct trajectories of adherence was selected: adherent (30.5%), gradual decline (21.6%), gaps in adherence (21.2%), and rapid decline (26.7%). Overall, 71% of patients followed a nonadherent trajectory. The multinomial logistic regression model assessed that patients with health maintenance organization versus comprehensive plans were more likely to experience rapid decline, gradual decline, and gaps in adherence. Patients aged 55-64 versus 18-34 years were less likely to experience rapid decline in adherence, gradual decline in adherence, and gaps in adherence.

Conclusion

Approximately 70% of patients with T2D who initiated combination therapy followed nonadherent trajectories during the first year of treatment. For initial combination therapy users, targeted interventions are needed to enhance suboptimal adherence.

最近的临床试验数据表明，糖尿病患者早期使用联合治疗对血糖控制有更持久的效果。然而，与早期使用联合治疗相关的多药方案的复杂性使得依从性更具挑战性，并且联合治疗的依从性往往得不到充分的了解。目的：本研究旨在评估在抗糖尿病治疗开始的第一年，初始联合治疗使用者的依从性轨迹。方法采用2017-2019年Merative MarketScan研究数据库进行回顾性研究。Drug-naïve 2型糖尿病（T2D）患者接受初始联合治疗并持续参加商业或医疗保险计划。在30天内或同一天接受2种不同的降糖药物治疗的患者被确定为初始联合治疗使用者。依从性在指标日期后1年内使用覆盖天数的比例进行测量。使用基于组的轨迹模型（GBTM）来识别联合治疗使用者不同的纵向依从性模式。采用多项回归模型来检验与不依从轨迹相关的预测因子。结果共发现116597例drug-naïve T2D患者，其中14118例（12.1%）开始联合治疗。选择了4种不同的依从性轨迹：坚持（30.5%），逐渐下降（21.6%），依从间隙（21.2%）和快速下降（26.7%）。总体而言，71%的患者遵循非粘附轨迹。多项logistic回归模型评估了健康维持组织与综合计划的患者更有可能经历快速下降、逐渐下降和依从性差距。55-64岁的患者与18-34岁的患者相比，不太可能经历依从性的快速下降、逐渐下降和依从性的差距。结论：在开始联合治疗的T2D患者中，大约70%的患者在治疗的第一年遵循非粘附性轨迹。对于最初的联合治疗使用者，需要有针对性的干预措施来增强次优依从性。

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引用次数: 0

Impact of glucagon-like peptide-1 receptor agonist or glucagon-like peptide-1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonists After bariatric surgery in the veteran population 胰高血糖素样肽-1受体激动剂或胰高血糖素样肽-1受体激动剂/葡萄糖依赖性胰岛素多肽受体激动剂对退伍军人减肥手术后的影响

JAPhA Pharmacotherapy

Pub Date : 2025-07-30 DOI: 10.1016/j.japhar.2025.100020

Sara Corum, Timothy Morgan, Ashley Thomas

Background

Obesity is a progressive chronic disease that increases the risk of metabolic complications. Bariatric surgery is recommended alongside comprehensive lifestyle interventions for patients with a body mass index (BMI) of > 40 kg/m², BMI of > 35 kg/m² with obesity-related comorbidities, or BMI of > 30 kg/m² with a history of type 2 diabetes mellitus (T2DM). Bariatric procedures result in weight loss and improved metabolic outcomes, although weight regain can occur after surgery. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and GLP-1 RA/glucose-dependent insulinotropic polypeptide receptor agonists (GIP RAs) have emerged as effective injectable therapies for weight loss and management of obesity-related comorbidities.

Objective

This project evaluated the efficacy and tolerability of GLP-1 RA and GLP-1 RA/GIP RA therapy after bariatric surgery.

Methods

This single-center, retrospective project included patients who underwent bariatric surgery, were initiated on GLP-1 RA or GLP-1/GIP RA at least 1 year after surgery, and were on therapy for at least 6 months. The primary outcome was the percentage change in body weight from initiation of therapy to 6 months after. Secondary outcomes included the percentage of patients achieving ≥ 5%, ≥ 10%, or ≥ 15% reduction in weight; time from bariatric surgery to therapy initiation; discontinuation or dose reduction of therapy; and weight change comparison between patients with a history of T2DM and not enrolled in a weight loss clinic compared with those enrolled in a weight loss clinic.

Results

Fifty patients met the inclusion criteria. The mean percentage weight change at 6 months was −8.4%. For percentage weight reduction, 16 patients achieved ≥ 5%, 13 achieved ≥ 10%, and 7 achieved ≥ 15%. Median time from surgery to initiation of therapy was 111 months. Adverse events occurred in 3 patients (6%).

Conclusion

Overall, in patients receiving GLP-1 RA at least 1 year after bariatric surgery, additional weight loss was observed with minimal reported adverse events.

背景：肥胖是一种进行性慢性疾病，可增加代谢并发症的风险。对于体重指数（BMI）为40 kg/m2、BMI为35 kg/m2并伴有肥胖相关合并症或BMI为30 kg/m2并有2型糖尿病（T2DM）病史的患者，建议在进行综合生活方式干预的同时进行减肥手术。减肥手术可以减轻体重并改善代谢结果，尽管手术后可能会出现体重反弹。胰高血糖素样肽-1受体激动剂（GLP-1 RAs）和GLP-1 RA/葡萄糖依赖性胰岛素性多肽受体激动剂（GIP RAs）已成为减肥和肥胖相关合并症管理的有效注射疗法。目的评价减肥手术后GLP-1 RA及GLP-1 RA/GIP RA治疗的疗效和耐受性。方法：本单中心回顾性研究纳入了接受减肥手术的患者，术后至少1年开始使用GLP-1 RA或GLP-1/GIP RA，治疗至少6个月。主要结局是从治疗开始到治疗后6个月体重的百分比变化。次要结局包括患者体重减轻≥5%、≥10%或≥15%的百分比；从减肥手术到治疗开始的时间；停止或减少治疗剂量；有2型糖尿病病史但未参加减肥诊所的患者与参加减肥诊所的患者之间的体重变化比较。结果50例患者符合纳入标准。6个月时体重变化的平均百分比为- 8.4%。体重减轻百分比方面，16例达到≥5%，13例达到≥10%，7例达到≥15%。从手术到开始治疗的中位时间为111个月。不良事件发生3例（6%）。总体而言，在减肥手术后至少1年接受GLP-1 RA的患者中，观察到额外的体重减轻，报告的不良事件最少。

{"title":"Impact of glucagon-like peptide-1 receptor agonist or glucagon-like peptide-1 receptor agonist/glucose-dependent insulinotropic polypeptide receptor agonists After bariatric surgery in the veteran population","authors":"Sara Corum, Timothy Morgan, Ashley Thomas","doi":"10.1016/j.japhar.2025.100020","DOIUrl":"10.1016/j.japhar.2025.100020","url":null,"abstract":"<div><h3>Background</h3><div>Obesity is a progressive chronic disease that increases the risk of metabolic complications. Bariatric surgery is recommended alongside comprehensive lifestyle interventions for patients with a body mass index (BMI) of > 40 kg/m<sup>2</sup>, BMI of > 35 kg/m<sup>2</sup> with obesity-related comorbidities, or BMI of > 30 kg/m<sup>2</sup> with a history of type 2 diabetes mellitus (T2DM). Bariatric procedures result in weight loss and improved metabolic outcomes, although weight regain can occur after surgery. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and GLP-1 RA/glucose-dependent insulinotropic polypeptide receptor agonists (GIP RAs) have emerged as effective injectable therapies for weight loss and management of obesity-related comorbidities.</div></div><div><h3>Objective</h3><div>This project evaluated the efficacy and tolerability of GLP-1 RA and GLP-1 RA/GIP RA therapy after bariatric surgery.</div></div><div><h3>Methods</h3><div>This single-center, retrospective project included patients who underwent bariatric surgery, were initiated on GLP-1 RA or GLP-1/GIP RA at least 1 year after surgery, and were on therapy for at least 6 months. The primary outcome was the percentage change in body weight from initiation of therapy to 6 months after. Secondary outcomes included the percentage of patients achieving ≥ 5%, ≥ 10%, or ≥ 15% reduction in weight; time from bariatric surgery to therapy initiation; discontinuation or dose reduction of therapy; and weight change comparison between patients with a history of T2DM and not enrolled in a weight loss clinic compared with those enrolled in a weight loss clinic.</div></div><div><h3>Results</h3><div>Fifty patients met the inclusion criteria. The mean percentage weight change at 6 months was −8.4%. For percentage weight reduction, 16 patients achieved ≥ 5%, 13 achieved ≥ 10%, and 7 achieved ≥ 15%. Median time from surgery to initiation of therapy was 111 months. Adverse events occurred in 3 patients (6%).</div></div><div><h3>Conclusion</h3><div>Overall, in patients receiving GLP-1 RA at least 1 year after bariatric surgery, additional weight loss was observed with minimal reported adverse events.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 4","pages":"Article 100020"},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing intraoperative administration of long-acting bupivacaine, multimodal cocktails, and local anesthetics for postoperative pain management 比较术中给药长效布比卡因、多模态鸡尾酒和局麻药对术后疼痛的控制

JAPhA Pharmacotherapy

Pub Date : 2025-07-01 DOI: 10.1016/j.japhar.2025.100019

Gabriella A. Perez, Alexander D. Schroeder, Daniel R. Fassett, Matthew W. Todd, Leilanie Y. Crespo Hernández, Francisco G. Perez Diaz, Oscar Santalo

Background

Liposomal bupivacaine (LB) has gained popularity for its reported analgesic effects lasting up to 72 hours. However, multimodal local anesthetic cocktails (MCs) may offer comparable pain control with potential cost savings and opioid-sparing benefits.

Objectives

This study compared postoperative pain outcomes with LB versus MCs such as ropivacaine-epinephrine-clonidine-ketorolac, bupivacaine-epinephrine-dexamethasone, bupivacaine-meloxicam, and traditional local anesthetics (LAs) such as lidocaine and bupivacaine.

Setting and participants

This retrospective, observational study included patients who underwent outpatient and inpatient procedures between August 1, 2023, and January 31, 2024.

Outcome measures

The primary outcome was postoperative day (POD) 2 pain scores. Secondary outcomes included total morphine milliequivalents (MMEs) administered within 72 hours and projected cost savings. Participants were excluded if they were younger than 18 years, lacked documented pain scores or MME data, had a history of chronic pain, or were pregnant.

Results

Of 27,878 patients, 265 were evaluated, and 174 met the inclusion criteria. Fifty-one received LB, 73 received MCs, and 50 received LAs. POD 2 pain scores for the LB, MC, and LA groups were not statistically different (P = 0.41), with averages of 4.69, 5.05, and 4.42, respectively. Total MMEs were also similar across groups, with a median total of 48.53, 51.16, and 40.10 for LB, MCs, and LAs, respectively (P = 0.58). Our cost analysis projected annualized savings of approximately $2.8 million and average patient savings of $46,500 per surgical procedure.

Conclusion

These findings suggest that MCs are a cost-effective alternative to LB with comparable analgesic effects.

布比卡因脂质体（LB）因其持续长达72小时的镇痛作用而受到欢迎。然而，多模式局部麻醉鸡尾酒（MCs）可能提供类似的疼痛控制，具有潜在的成本节约和阿片类药物节约的好处。目的：本研究比较LB与MCs（如罗哌卡因-肾上腺素-氯定-酮洛拉、布比卡因-肾上腺素-地塞米松、布比卡因-美洛昔康）和传统局麻药（如利多卡因和布比卡因）的术后疼痛结局。背景和参与者：这项回顾性观察性研究纳入了2023年8月1日至2024年1月31日期间接受门诊和住院治疗的患者。主要观察指标为术后日（POD） 2疼痛评分。次要结局包括72小时内吗啡总毫当量（MMEs）和预计的成本节约。如果参与者年龄小于18岁，缺乏记录在案的疼痛评分或MME数据，有慢性疼痛史或怀孕，则排除在外。结果27878例患者中，265例纳入评估，174例符合纳入标准。51人接受LB治疗，73人接受mc治疗，50人接受LAs治疗。LB组、MC组、LA组POD 2疼痛评分差异无统计学意义（P = 0.41），平均分别为4.69、5.05、4.42。各组间的mme总数也相似，LB、MCs和LAs的中位数分别为48.53、51.16和40.10 （P = 0.58）。我们的成本分析预计每年节省约280万美元，平均每例手术为患者节省46,500美元。结论MCs是一种具有相当镇痛效果的低成本替代LB的药物。

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引用次数: 0

Real-world safety profile of lecanemab: A disproportionality analysis of adverse events in the FDA adverse event reporting system lecanemab的实际安全性概况：FDA不良事件报告系统中不良事件的歧化分析

JAPhA Pharmacotherapy

Pub Date : 2025-04-01 DOI: 10.1016/j.japhar.2025.100015

Jayoung Han, Yuan Fang, Nicole Campbell

Background

Lecanemab, an antiamyloid monoclonal antibody, has emerged as a treatment option for Alzheimer disease. However, there is a pressing need for real-world evidence to inform clinical practice, particularly regarding its safety profile.

Objectives

This study aimed to analyze adverse events (AEs) associated with lecanemab using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods

All cases reporting AEs were included if reported during the study period, from January 1, 2023, to June 30, 2024, during which a total of 1,307,937 cases were reported in the FAERS database. A disproportionality analysis was conducted to assess adverse reactions associated with lecanemab. Reporting odds ratios (RORs) with 95% CIs were extracted from OpenVigil 2.1-MedDRA-v24 for lecanemab-related events.

Results

The analysis identified a total of 1679 AEs associated with lecanemab during the study period. The strongest safety signal was observed for amyloid-related imaging abnormalities (ARIAs), particularly ARIA with hemosiderin deposits in the brain parenchyma or on the pial surface (microhemorrhages, ROR 11,221.5 [95% CI 5706.2–22,067.5]) and ARIA with brain edema or sulcal effusion (edema/effusion, ROR 8927.3 [95% CI 5243.6–15,199.1]). Other notable AEs included infusion-related reactions (ROR 24.9 [95% CI 18.9–32.8]), headache (ROR 10.2 [95% CI 8.6–12.2]), and confusional states (ROR 15.0 [95% CI 11.4–19.7]).

Conclusion

This study underscores the importance of vigilant monitoring for ARIA and other neurologic and psychiatric AEs associated with lecanemab in real-world clinical settings. The findings highlight the need for ongoing postmarket surveillance to ensure patient safety and guide clinical decision making.

lecanemab是一种抗淀粉样蛋白单克隆抗体，已成为治疗阿尔茨海默病的一种选择。然而，迫切需要真实世界的证据来告知临床实践，特别是关于其安全性。本研究旨在利用美国食品和药物管理局不良事件报告系统（FAERS）数据库分析与莱卡耐单抗相关的不良事件（ae）。方法纳入研究期间（2023年1月1日至2024年6月30日）报告的所有ae病例，FAERS数据库共报告1,307,937例ae病例。进行歧化分析以评估与莱卡耐单抗相关的不良反应。从OpenVigil 2.1-MedDRA-v24中提取了95% ci的报告优势比（RORs），用于研究lecanemab相关事件。结果在研究期间共鉴定出1679例与lecanemab相关的ae。淀粉样蛋白相关影像学异常（ARIAs）的安全性信号最强，尤其是伴有含铁血黄素沉积在脑实质或脑顶表面的ARIAs（微出血，ROR 11,221.5 [95% CI 5706.2-22,067.5]）和伴有脑水肿或脑沟积液的ARIAs（水肿/积液，ROR 8927.3 [95% CI 5243.6-15,199.1]）。其他显著的ae包括输注相关反应（ROR 24.9 [95% CI 18.9-32.8]）、头痛（ROR 10.2 [95% CI 8.6-12.2]）和精神错乱状态（ROR 15.0 [95% CI 11.4-19.7]）。结论：本研究强调了在现实世界的临床环境中警惕监测ARIA和其他与莱卡耐单抗相关的神经和精神不良事件的重要性。研究结果强调需要持续的上市后监测，以确保患者安全并指导临床决策。

{"title":"Real-world safety profile of lecanemab: A disproportionality analysis of adverse events in the FDA adverse event reporting system","authors":"Jayoung Han, Yuan Fang, Nicole Campbell","doi":"10.1016/j.japhar.2025.100015","DOIUrl":"10.1016/j.japhar.2025.100015","url":null,"abstract":"<div><h3>Background</h3><div>Lecanemab, an antiamyloid monoclonal antibody, has emerged as a treatment option for Alzheimer disease. However, there is a pressing need for real-world evidence to inform clinical practice, particularly regarding its safety profile.</div></div><div><h3>Objectives</h3><div>This study aimed to analyze adverse events (AEs) associated with lecanemab using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.</div></div><div><h3>Methods</h3><div>All cases reporting AEs were included if reported during the study period, from January 1, 2023, to June 30, 2024, during which a total of 1,307,937 cases were reported in the FAERS database. A disproportionality analysis was conducted to assess adverse reactions associated with lecanemab. Reporting odds ratios (RORs) with 95% CIs were extracted from OpenVigil 2.1-MedDRA-v24 for lecanemab-related events.</div></div><div><h3>Results</h3><div>The analysis identified a total of 1679 AEs associated with lecanemab during the study period. The strongest safety signal was observed for amyloid-related imaging abnormalities (ARIAs), particularly ARIA with hemosiderin deposits in the brain parenchyma or on the pial surface (microhemorrhages, ROR 11,221.5 [95% CI 5706.2–22,067.5]) and ARIA with brain edema or sulcal effusion (edema/effusion, ROR 8927.3 [95% CI 5243.6–15,199.1]). Other notable AEs included infusion-related reactions (ROR 24.9 [95% CI 18.9–32.8]), headache (ROR 10.2 [95% CI 8.6–12.2]), and confusional states (ROR 15.0 [95% CI 11.4–19.7]).</div></div><div><h3>Conclusion</h3><div>This study underscores the importance of vigilant monitoring for ARIA and other neurologic and psychiatric AEs associated with lecanemab in real-world clinical settings. The findings highlight the need for ongoing postmarket surveillance to ensure patient safety and guide clinical decision making.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 2","pages":"Article 100015"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluating the safety of daptomycin coadministered with statin medications 评价达托霉素与他汀类药物合用的安全性

JAPhA Pharmacotherapy

Pub Date : 2025-04-01 DOI: 10.1016/j.japhar.2025.100017

Tyler M. Mitzner, Michael McCormick, Krissy M. Lentz, Ryan Tomlin, Kyle J. Schmidt, Lisa E. Dumkow

Background

Conflicting clinical evidence and prescribing recommendations exist regarding the safety of daptomycin when coadministered with statin medications. In addition, recommendations to hold statins during daptomycin therapy do not account for atherosclerotic cardiovascular disease (ASCVD) risk. Because of this, the practice of holding or continuing statins during daptomycin therapy is variable among providers.

Objectives

This study aimed to compare the musculoskeletal and cardiovascular safety of daptomycin and statin coadministration versus monotherapy and assess the appropriateness of monitoring during daptomycin infusion therapy, including creatine kinase (CK) and musculoskeletal symptoms, and the resumption of statins held during daptomycin therapy.

Methods

This retrospective cohort study included patients who were prescribed a statin medication and daptomycin therapy. The primary outcome was to compare daptomycin discontinuation owing to suspected musculoskeletal toxicity between patients who had their statin held and received daptomycin monotherapy (monotherapy group) and those who received daptomycin coadministered with statins (coadministered group). Secondary outcomes included evaluating CK monitoring practices, ASCVD events, and the resumption of held statins at the completion of daptomycin therapy.

Results

A total of 74 patients were included (monotherapy, n = 64; coadministered, n = 10). No statistically significant differences were observed between the 2 groups regarding daptomycin discontinuation owing to suspected musculoskeletal toxicity (6.3% monotherapy vs. 10% coadministered, P = 0.527). One patient in the monotherapy group had an ASCVD event during daptomycin therapy; none occurred within the coadministered group. Within the monotherapy group, 9 patients (14.1%) did not have documentation of statin resumption and 22 (34.4%) saw a delay of 4 or more weeks in statin resumption after daptomycin completion.

Conclusion

Patients who received daptomycin coadministration with statin therapy did not experience more musculoskeletal toxicity than patients who received daptomycin monotherapy. Owing to the risk of ASCVD events and potential for errors and delays in resumption, statins should be continued during daptomycin therapy, especially in high-risk patients.

背景：关于达托霉素与他汀类药物合用的安全性，存在相互矛盾的临床证据和处方建议。此外，在达托霉素治疗期间保留他汀类药物的建议并不能解释动脉粥样硬化性心血管疾病（ASCVD）的风险。正因为如此，在达托霉素治疗期间保持或继续使用他汀类药物的做法在提供者之间是可变的。目的：本研究旨在比较达托霉素和他汀联合使用与单药治疗的肌肉骨骼和心血管安全性，并评估在达托霉素输注治疗期间监测的适宜性，包括肌酸激酶（CK）和肌肉骨骼症状，以及在达托霉素治疗期间恢复使用他汀类药物。方法本回顾性队列研究纳入了接受他汀类药物和达托霉素治疗的患者。主要结果是比较由于怀疑肌肉骨骼毒性而停用达托霉素的患者中，保留他汀类药物并接受达托霉素单药治疗（单药治疗组）和接受达托霉素与他汀类药物联合治疗（联合治疗组）的患者。次要结局包括评估CK监测实践，ASCVD事件，以及在达托霉素治疗完成后恢复使用他汀类药物。结果共纳入74例患者(单药治疗，n = 64；共给药，n = 10)。两组因怀疑肌肉骨骼毒性而停药达托霉素的差异无统计学意义（6.3%单药vs 10%共给药，P = 0.527）。单药治疗组有1例患者在达托霉素治疗期间发生ASCVD事件；在共同管理组中没有发生。在单药治疗组中，9名患者（14.1%）没有恢复他汀类药物的记录，22名患者（34.4%）在达托霉素停用后延迟4周或更长时间恢复他汀类药物。结论达托霉素联合他汀类药物治疗的患者肌肉骨骼毒性并不比单药治疗的患者大。由于ASCVD事件的风险和潜在的错误和延迟恢复，他汀类药物应在达托霉素治疗期间继续使用，特别是在高危患者中。

{"title":"Evaluating the safety of daptomycin coadministered with statin medications","authors":"Tyler M. Mitzner, Michael McCormick, Krissy M. Lentz, Ryan Tomlin, Kyle J. Schmidt, Lisa E. Dumkow","doi":"10.1016/j.japhar.2025.100017","DOIUrl":"10.1016/j.japhar.2025.100017","url":null,"abstract":"<div><h3>Background</h3><div>Conflicting clinical evidence and prescribing recommendations exist regarding the safety of daptomycin when coadministered with statin medications. In addition, recommendations to hold statins during daptomycin therapy do not account for atherosclerotic cardiovascular disease (ASCVD) risk. Because of this, the practice of holding or continuing statins during daptomycin therapy is variable among providers.</div></div><div><h3>Objectives</h3><div>This study aimed to compare the musculoskeletal and cardiovascular safety of daptomycin and statin coadministration versus monotherapy and assess the appropriateness of monitoring during daptomycin infusion therapy, including creatine kinase (CK) and musculoskeletal symptoms, and the resumption of statins held during daptomycin therapy.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included patients who were prescribed a statin medication and daptomycin therapy. The primary outcome was to compare daptomycin discontinuation owing to suspected musculoskeletal toxicity between patients who had their statin held and received daptomycin monotherapy (monotherapy group) and those who received daptomycin coadministered with statins (coadministered group). Secondary outcomes included evaluating CK monitoring practices, ASCVD events, and the resumption of held statins at the completion of daptomycin therapy.</div></div><div><h3>Results</h3><div>A total of 74 patients were included (monotherapy, n = 64; coadministered, n = 10). No statistically significant differences were observed between the 2 groups regarding daptomycin discontinuation owing to suspected musculoskeletal toxicity (6.3% monotherapy vs. 10% coadministered, <em>P</em> = 0.527). One patient in the monotherapy group had an ASCVD event during daptomycin therapy; none occurred within the coadministered group. Within the monotherapy group, 9 patients (14.1%) did not have documentation of statin resumption and 22 (34.4%) saw a delay of 4 or more weeks in statin resumption after daptomycin completion.</div></div><div><h3>Conclusion</h3><div>Patients who received daptomycin coadministration with statin therapy did not experience more musculoskeletal toxicity than patients who received daptomycin monotherapy. Owing to the risk of ASCVD events and potential for errors and delays in resumption, statins should be continued during daptomycin therapy, especially in high-risk patients.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 2","pages":"Article 100017"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overall survival of patients over 65 years old with lung cancer receiving programmed death-1 inhibitors and antibiotics 接受程序性死亡-1抑制剂和抗生素治疗的65岁以上肺癌患者的总生存率

JAPhA Pharmacotherapy

Pub Date : 2025-01-01 DOI: 10.1016/j.japhar.2025.100012

Valerie S. Hughes, Eric J. Vick, Rowena Schwartz, Roman Jandarov, Jeff J. Guo, Alex C. Lin, Ana L. Hincapie

Background

Programmed death-1 (PD-1) inhibitors have advanced treatment of patients with non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, and other cancers. Lung cancer is commonly diagnosed at the advanced stage in an older adult patient population; therefore, many contributing factors can influence the treatment response. Not all patients respond to PD-1 treatment and even less is known for aging patients with comorbidities, altered gut microbiome, and multiple concomitant medications.

Objective

This study aimed to evaluate overall survival (OS) in older adult patients with lung cancer receiving PD-1 inhibitors and medications known to affect the gut microbiome.

Methods

Surveillance, Epidemiology, and End Results–Medicare is a database that links tumor registry data with Medicare enrollment and claims files. The study cohort was determined based on lung cancer histology, claims for nivolumab or pembrolizumab, and continuous enrollment. Oral antibiotic (Ab) claims were identified in the Part D file and assigned to 14-, 30-, or 60-day comparison groups. Patient characteristics between PD-1 and Ab exposure at 14, 30, and 60 days were assessed by chi-square test. The association between OS and Ab was analyzed using the Cox proportional hazards model and Kaplan-Meier curves.

Results

We identified 3445 patients who had lung cancer and received PD-1 inhibitors from 2014 to 2017. Of those patients, 1702 (49%) received an oral Ab within 60 days of starting the PD-1 therapy. Ab use during the initiation of PD-1 treatment was associated with shorter OS when given within 60 days of initiation of treatment (hazard ratio 1.273 [95% confidence interval 1.104–1.469], P = 0.0009) than patients with no Ab claim within 180 days of index.

Conclusion

Utilization of immunotherapy is increasing in the Medicare population and these patients commonly have age-related changes to the immune systems and microbiome. These results provide OS estimates for older adult patients with lung cancer treated with PD-1 and receiving medications known to alter important gut microbiome diversity. The complex interactions of the immune system, microbiome, and immunotherapy response are key for the effective treatment of patients with NSCLC.

程序性死亡-1 （PD-1）抑制剂可用于非小细胞肺癌（NSCLC）、黑色素瘤、肾细胞癌和其他癌症的晚期治疗。肺癌通常在老年患者人群中被诊断为晚期；因此，许多因素可以影响治疗反应。并非所有患者都对PD-1治疗有反应，对于患有合并症、肠道微生物群改变和多种合用药物的老年患者，我们所知的就更少了。目的：本研究旨在评估接受PD-1抑制剂和已知影响肠道微生物组的药物治疗的老年肺癌患者的总生存率（OS）。方法：监测、流行病学和最终结果——医疗保险是一个将肿瘤登记数据与医疗保险登记和索赔文件联系起来的数据库。研究队列是根据肺癌组织学、纳武单抗或派姆单抗的声明和持续入组确定的。口服抗生素（Ab）索赔在D部分文件中确定，并分配到14天，30天或60天的对照组。采用卡方检验评估PD-1和Ab暴露在14,30和60天的患者特征。采用Cox比例风险模型和Kaplan-Meier曲线分析OS与Ab之间的相关性。2014年至2017年，我们确定了3445例肺癌患者并接受了PD-1抑制剂治疗。在这些患者中，1702例（49%）在开始PD-1治疗的60天内接受了口服Ab。与在PD-1治疗开始后的180天内未使用Ab的患者相比，在开始治疗后60天内使用Ab与更短的OS相关（风险比1.273[95%置信区间1.104-1.469],P = 0.0009）。结论免疫治疗在医保人群中的应用正在增加，这些患者通常存在与年龄相关的免疫系统和微生物组变化。这些结果为接受PD-1治疗并接受已知可改变重要肠道微生物群多样性的药物治疗的老年肺癌患者提供了OS估计。免疫系统、微生物组和免疫治疗反应之间复杂的相互作用是有效治疗非小细胞肺癌的关键。

{"title":"Overall survival of patients over 65 years old with lung cancer receiving programmed death-1 inhibitors and antibiotics","authors":"Valerie S. Hughes, Eric J. Vick, Rowena Schwartz, Roman Jandarov, Jeff J. Guo, Alex C. Lin, Ana L. Hincapie","doi":"10.1016/j.japhar.2025.100012","DOIUrl":"10.1016/j.japhar.2025.100012","url":null,"abstract":"<div><h3>Background</h3><div>Programmed death-1 (PD-1) inhibitors have advanced treatment of patients with non–small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, and other cancers. Lung cancer is commonly diagnosed at the advanced stage in an older adult patient population; therefore, many contributing factors can influence the treatment response. Not all patients respond to PD-1 treatment and even less is known for aging patients with comorbidities, altered gut microbiome, and multiple concomitant medications.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate overall survival (OS) in older adult patients with lung cancer receiving PD-1 inhibitors and medications known to affect the gut microbiome.</div></div><div><h3>Methods</h3><div>Surveillance, Epidemiology, and End Results–Medicare is a database that links tumor registry data with Medicare enrollment and claims files. The study cohort was determined based on lung cancer histology, claims for nivolumab or pembrolizumab, and continuous enrollment. Oral antibiotic (Ab) claims were identified in the Part D file and assigned to 14-, 30-, or 60-day comparison groups. Patient characteristics between PD-1 and Ab exposure at 14, 30, and 60 days were assessed by chi-square test. The association between OS and Ab was analyzed using the Cox proportional hazards model and Kaplan-Meier curves.</div></div><div><h3>Results</h3><div>We identified 3445 patients who had lung cancer and received PD-1 inhibitors from 2014 to 2017. Of those patients, 1702 (49%) received an oral Ab within 60 days of starting the PD-1 therapy. Ab use during the initiation of PD-1 treatment was associated with shorter OS when given within 60 days of initiation of treatment (hazard ratio 1.273 [95% confidence interval 1.104–1.469], <em>P</em> = 0.0009) than patients with no Ab claim within 180 days of index.</div></div><div><h3>Conclusion</h3><div>Utilization of immunotherapy is increasing in the Medicare population and these patients commonly have age-related changes to the immune systems and microbiome. These results provide OS estimates for older adult patients with lung cancer treated with PD-1 and receiving medications known to alter important gut microbiome diversity. The complex interactions of the immune system, microbiome, and immunotherapy response are key for the effective treatment of patients with NSCLC.</div></div>","PeriodicalId":100736,"journal":{"name":"JAPhA Pharmacotherapy","volume":"2 1","pages":"Article 100012"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144195003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alignment of counseling around topical steroids will improve morbidity associated with lichen sclerosus 围绕局部类固醇的咨询将改善与硬化地衣相关的发病率

JAPhA Pharmacotherapy

Pub Date : 2024-12-01 DOI: 10.1016/j.japhar.2025.100010

Margaret E. Greer, Paras P. Vakharia, Melissa M. Mauskar

Ultrapotent topical steroids are the first-line treatment for lichen sclerosus, a chronic inflammatory disease that most commonly affects the genital and anal regions. Lichen sclerosus can cause profound morbidity and can progress to squamous cell carcinoma. Therefore, treatment is essential to mitigate these complications. Despite the accessibility, relative affordability, and safety profiles of topical steroids, many clinicians, pharmacists, and patients are hesitant to use them. This paper outlines the importance of chronic steroid use for managing lichen sclerosus to prevent disease sequelae and aims to educate readers on ways physicians and pharmacists can mitigate steroid phobia.

超高效外用类固醇是硬化地衣的一线治疗方法，硬化地衣是一种最常影响生殖器和肛门区域的慢性炎症性疾病。硬化性地衣可引起严重的发病率，并可发展为鳞状细胞癌。因此，治疗对于减轻这些并发症至关重要。尽管外用类固醇具有可及性、相对可负担性和安全性，但许多临床医生、药剂师和患者对使用它们犹豫不决。本文概述了慢性类固醇使用对管理硬化地衣预防疾病后遗症的重要性，旨在教育医生和药剂师如何减轻类固醇恐惧症的读者。

引用次数: 0

Guidance on calculating doses of antineoplastic agents for transgender and gender-expansive patients taking gender-affirming hormone therapy 跨性别和性别扩张患者接受性别确认激素治疗的抗肿瘤药物剂量计算指南

JAPhA Pharmacotherapy

Pub Date : 2024-10-01 DOI: 10.1016/j.japhar.2024.100009

Andréa C. LeVoir, Erica C. Stumpf, Wiktoria Bogdanska, Maly Fenelus, Ilya G. Glezerman, Lubaina Presswala, Boglarka Gyurkocza, Koshy Alexander, Kelly Haviland

Background

There is currently no formal guidance for calculating chemotherapy in transgender and gender-expansive patients taking gender-affirming hormone therapy (GAHT). It is necessary to develop a method that ensures that chemotherapy dosing and treatment are both safe and effective in this population.

Objectives

To identify guidance for clinicians to evaluate renal function to determine appropriate chemotherapy doses in transgender and gender-expansive adult patients taking GAHT.

Methods

The Lesbian, Gay, Bisexual, Transgender, Queer, and Intersex (LGBTQI+) Clinical Advisory Committee at a large comprehensive cancer center conducted an unstructured review in PubMed to identify current literature surrounding chemotherapy and medication dosing in patients taking GAHT.

Results

The use of sex assigned at birth-dependent methods to define renal dosing may not be accurate for transgender and gender-expansive patients. Based on the limited published literature, a multidisciplinary team developed guidance on calculating chemotherapy dosing in patients who are taking GAHT. Gaps not addressed by available literature were evaluated by a panel of experts, and their recommendations were included.

Conclusion

A guideline was produced based on the available data; however, additional research is needed to better define the physiologic changes that occur with GAHT and how those changes affect renal function and current surrogates that are used to estimate renal function.

目前还没有正式的指南来计算跨性别和性别扩张患者接受性别确认激素治疗（GAHT）的化疗费用。有必要开发一种方法，确保化疗剂量和治疗在这一人群中既安全又有效。目的为临床医生评估接受GAHT的跨性别和性别扩张成年患者的肾功能以确定合适的化疗剂量提供指导。方法某大型综合性癌症中心的女同性恋、男同性恋、双性恋、变性人、酷儿和双性人（LGBTQI+）临床咨询委员会在PubMed上进行了一项非结构化的综述，以确定目前有关接受GAHT患者化疗和药物剂量的文献。结果使用出生依赖的性别分配方法来确定肾脏剂量对于跨性别和性别扩张患者可能不准确。基于有限的已发表文献，一个多学科团队制定了计算GAHT患者化疗剂量的指南。现有文献未解决的差距由专家小组评估，并纳入他们的建议。结论根据现有资料制定了指南；然而，需要进一步的研究来更好地定义GAHT发生的生理变化，以及这些变化如何影响肾功能和目前用于估计肾功能的替代品。

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引用次数: 0