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A Network Meta-Analysis of Vasodilator Therapies in Pulmonary Hypertension Patients Undergoing Mitral Valve Replacement Surgery: Insights for Optimizing Hemodynamics. 对接受二尖瓣置换手术的肺动脉高压患者使用血管扩张剂治疗的网络 Meta 分析:优化血液动力学的启示。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-16 DOI: 10.1007/s40261-024-01404-9
Amr Elrosasy, Ahmed Maher, Abdelraouf Ramadan, Nada G Hamam, Mohamed Soliman, Sara K Kamal, Beshoy Emad Milik, Abdullah Ali Shahat, Menna Nabil Kamel, Ahmed Abdeltawab Ali, Loay Abdelnabi Hassan, Ahmed Zabady, Mohamed Abo Zeid, Wael Abdelmottaleb, Sameh Nassar

Background and objective: Pulmonary hypertension (PH) is a progressive hemodynamic condition associated with significant morbidity and mortality, especially in patients undergoing cardiac surgery. Therefore, the objective of this network meta-analysis (NMA) is to compare the efficacy of various pulmonary vasodilators in perioperative control of PH among patients undergoing mitral valve replacement surgery (MVRS), aiming to address the existing knowledge gap and improve perioperative outcomes.

Methods: Electronic databases including PubMed, Cochrane Central Registry of Controlled Trials, Scopus, Embase, and Web of Science (WOS) from inception to 17 September 2024. Only randomized controlled trials (RCTs) evaluating vasodilators in PH patients undergoing MVRS were included. We used netmeta package in RStudio to analyze the outcome data with their corresponding mean difference (MD) and confidence intervals (CI).

Results: Seventeen RCTs including 862 patients were analyzed. Prostacyclin, nitric oxide (NO), and sodium nitroprusside (SN) significantly reduced mean pulmonary arterial pressure with effect sizes [MD, 95% confidence interval (CI)] of (11.77, - 18.78; - 4.76; - 8.3, - 15.9; - 0.6; - 11.02, - 20.1; - 3.8, respectively). While no treatment showed significant efficacy on pulmonary capillary wedge pressure, systolic pulmonary arterial pressure, or heart rate, nitroglycerin, NO, and prostacyclin, showed significant increases in cardiac index with effect sizes (MD, 95% CI) of (1, 0.3; 1.7; 1.2 0.8; 1.6; 1.2 0.8; 1.6, respectively). Additionally, NO, prostacyclin, SN, and nitroglycerin demonstrated significant reductions in systemic vascular resistance (SVR), with effect sizes of. (- 0.54, - 0.82; - 0.26, - 0.37, - 0.65; - 0.09; - 0.47, - 0.77; - 0.16; - 0.14, - 0.24; - 0.03, respectively).

Conclusions: This NMA highlights prostacyclin, nitroglycerin, NO, and SN as consistently effective in improving hemodynamics for patients with PH undergoing MVRS, and provides valuable insights for surgeons to choose the suitable vasodilator for these surgeries. However, limitations and the need for further RCTs are acknowledged.

背景和目的:肺动脉高压(PH)是一种进展性血流动力学疾病,与严重的发病率和死亡率有关,尤其是在接受心脏手术的患者中。因此,本网络荟萃分析(NMA)的目的是比较各种肺血管扩张剂对二尖瓣置换手术(MVRS)患者围手术期控制 PH 的疗效,以弥补现有的知识差距并改善围手术期的预后:电子数据库,包括 PubMed、Cochrane Central Registry of Controlled Trials、Scopus、Embase 和 Web of Science (WOS),从开始到 2024 年 9 月 17 日。仅纳入了对接受 MVRS 的 PH 患者使用血管扩张剂进行评估的随机对照试验(RCT)。我们使用 RStudio 中的 netmeta 软件包分析了结果数据及其相应的平均差(MD)和置信区间(CI):结果:分析了包括 862 名患者在内的 17 项 RCT。前列环素、一氧化氮(NO)和硝普钠(SN)可显著降低平均肺动脉压,其效应大小[MD,95% 置信区间(CI)]分别为(11.77,- 18.78;- 4.76;- 8.3,- 15.9;- 0.6;- 11.02,- 20.1;- 3.8)。虽然没有一种治疗方法对肺毛细血管楔压、肺动脉收缩压或心率有明显疗效,但硝酸甘油、NO 和前列环素却能显著增加心脏指数,其效应大小(MD,95% CI)分别为(1,0.3;1.7;1.2 0.8;1.6;1.2 0.8;1.6)。此外,NO、前列环素、SN 和硝酸甘油均可显著降低全身血管阻力(SVR),其效应大小分别为(- 0.54、- 0.54、- 0.54、- 0.54)。(分别为:- 0.54,- 0.82;- 0.26,- 0.37,- 0.65;- 0.09;- 0.47,- 0.77;- 0.16;- 0.14,- 0.24;- 0.03):该NMA突出显示了前列环素、硝酸甘油、NO和SN在改善接受MVRS的PH患者血液动力学方面的持续有效性,并为外科医生为这些手术选择合适的血管扩张剂提供了有价值的见解。然而,该研究还存在局限性,需要进一步开展研究性试验。
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引用次数: 0
A Phase I Clinical Trial to Evaluate the Bioequivalence of an Adalimumab Biosimilar Adalimumab-WIBP and Humira®. 评估阿达木单抗生物仿制药 Adalimumab-WIBP 和 Humira® 生物等效性的 I 期临床试验。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-15 DOI: 10.1007/s40261-024-01409-4
Shengling Hu, Yang Liu, Lu Yang, Yunkai Yang, Feiguang Long, Hongying Bao, Huijun Zhang, Xin Yue, Jiayou Zhang, Zejun Wang, Chaolin Huang, Jingli Wang, Liu Xia, Yongbing Pan, Yuntao Zhang, Fengyun Gong

Background and objectives: The high costs associated with biological agents often limit accessibility for many patients, whereas biosimilars allow the wider application of biological treatment. The objectives of this phase I clinical trial were to compare the pharmacokinetics, immunogenicity, and safety profiles of the biosimilar adalimumab-WIBP and the reference product Humira® and to assess the precision of the bioequivalence evaluation.

Methods: In this randomized, double-blind, parallel-group bioequivalence study, 164 healthy male Chinese participants were selected and randomly divided into two groups on a 1:1 ratio. The subjects were administered a single 40 mg subcutaneous dose of either adalimumab-WIBP or Humira®. Blood samples extracted at multiple intervals after administration were analyzed to interpret pharmacokinetic parameters, and any adverse events were documented. Alongside ensuring safety measures, the subjects were monitored for immunogenicity.

Results: The pharmacokinetic results demonstrated similar serum concentration-time curves in both groups. There were no significant differences in safety and no differences in immunogenicity profiles between the two groups. The bioequivalence was confirmed: the 90% confidence interval for the geometric mean ratio of the main pharmacokinetic parameters was within the range of 80-125%.

Conclusion: The trial indicated the bioequivalence between adalimumab-WIBP and the reference product Humira® based on pharmacokinetics, immunogenicity, and safety profile. These findings reinforce the use of the adalimumab-WIBP biosimilar as a possible therapeutic alternative to Humira®.

背景和目的:与生物制剂相关的高昂费用往往限制了许多患者对生物制剂的使用,而生物仿制药则可以使生物治疗得到更广泛的应用。这项 I 期临床试验的目的是比较阿达木单抗生物仿制药 WIBP 和参比产品 Humira® 的药代动力学、免疫原性和安全性,并评估生物等效性评价的精确性:在这项随机、双盲、平行组生物等效性研究中,我们选取了164名健康的中国男性受试者,按1:1的比例随机分为两组。受试者单次皮下注射40毫克阿达木单抗-WIBP或Humira®。在给药后多次抽取血液样本进行分析,以解读药代动力学参数,并记录任何不良事件。在确保安全的同时,还对受试者进行了免疫原性监测:药代动力学结果显示,两组受试者的血清浓度-时间曲线相似。结果:药代动力学结果表明,两组受试者的血清浓度-时间曲线相似,安全性无明显差异,免疫原性也无差异。生物等效性得到证实:主要药代动力学参数几何平均比的 90% 置信区间在 80-125% 之间:试验表明,根据药代动力学、免疫原性和安全性分析,阿达木单抗-WIBP与参比产品Humira®具有生物等效性。这些发现加强了阿达木单抗-WIBP生物类似药作为Humira®治疗替代品的可能性。
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引用次数: 0
A Single-Dose Study to Evaluate the Relative Bioavailability, Safety, and Tolerability of Monthly Extended-Release Buprenorphine at Alternative Injection Locations in Adult Participants with Opioid Use Disorder. 单剂量研究:评估阿片类药物使用失调症成年参与者在其他注射地点使用月度缓释丁丙诺啡的相对生物利用度、安全性和耐受性。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-14 DOI: 10.1007/s40261-024-01406-7
Celine M Laffont, Olga Lapeyra, Dipti Mangal, Robert Dobbins

Background and objectives: Buprenorphine extended-release monthly formulation (BUP-XR, SUBLOCADE®) is approved for treatment of moderate-to-severe opioid use disorder (OUD) following subcutaneous injection in the abdomen. This open-label pharmacokinetic study assessed three alternative injection locations (upper arm, thigh, buttocks) to offer additional flexibility considering the chronic nature of the disease and patient preferences.

Methods: Following stabilization on 12/3 mg/day of sublingual buprenorphine/naloxone for ≥ 7 days, participants with moderate-to-severe OUD were randomized to receive a single 300-mg BUP-XR injection in the upper arm, thigh, buttocks, or abdomen (reference). Serial blood samples were taken to measure buprenorphine plasma concentrations over 28 days and assess buprenorphine relative bioavailability. Safety evaluations included treatment-emergent adverse events and assessments of injection site pain, tenderness, erythema, induration, and swelling.

Results: A total of 88 participants received a single subcutaneous injection of 300-mg BUP-XR in the upper arm (N = 21), thigh (N = 23), buttocks (N = 22), or abdomen (N = 22); 81/88 (92%) completed the study. Buprenorphine plasma exposure (area under the plasma concentration-time curve over 28 days) was comparable across injection site groups with mean buprenorphine plasma concentrations sustained at approximately 2 ng/mL (therapeutic target concentration) or above. Buprenorphine maximum plasma concentration (Cmax) was approximately 39% and 52% higher after injection in the upper arm and thigh, respectively, versus the abdomen, while comparable between buttocks and abdomen. Higher Cmax values were not associated with an increased incidence of adverse events. Safety and injection site tolerability were comparable across injection groups.

Conclusions: These pharmacokinetic and safety findings support BUP-XR injection into the upper arm, thigh, and buttocks.

Trial registration: Clinicaltrials.gov: NCT05704543.

背景和目标:丁丙诺啡缓释月配方(BUP-XR,SUBLOCADE®)获准用于治疗中重度阿片类药物使用障碍(OUD),腹部皮下注射。这项开放标签药代动力学研究评估了三个替代注射位置(上臂、大腿、臀部),以提供更多灵活性,同时考虑到该疾病的慢性性质和患者的偏好:中度至重度 OUD 患者在稳定服用 12/3 毫克/天的丁丙诺啡/纳洛酮≥ 7 天后,被随机分配到上臂、大腿、臀部或腹部(参考)接受单次 300 毫克 BUP-XR 注射。在 28 天内连续采集血样以测量丁丙诺啡的血浆浓度,并评估丁丙诺啡的相对生物利用度。安全性评估包括治疗突发不良事件以及注射部位疼痛、触痛、红斑、压痕和肿胀评估:共有 88 名参与者在上臂(21 人)、大腿(23 人)、臀部(22 人)或腹部(22 人)单次皮下注射 300 毫克 BUP-XR;81/88(92%)人完成了研究。各注射部位组的丁丙诺啡血浆暴露量(28 天血浆浓度-时间曲线下面积)相当,平均丁丙诺啡血浆浓度维持在约 2 纳克/毫升(治疗目标浓度)或以上。上臂和大腿注射后的丁丙诺啡最大血浆浓度(Cmax)分别比腹部高出约 39% 和 52%,而臀部和腹部则相当。较高的 Cmax 值与不良事件发生率的增加无关。各注射组的安全性和注射部位耐受性相当:这些药代动力学和安全性研究结果支持在上臂、大腿和臀部注射 BUP-XR:试验注册:Clinicaltrials.gov:试验注册:Clinicaltrials.gov:NCT05704543。
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引用次数: 0
Efficacy of Intravenous Ferric Carboxymaltose in Heart Failure Patients with Iron Deficiency Anemia: A Meta-analysis of 6271 Patients. 缺铁性贫血心衰患者静脉注射羧甲基铁的疗效:对 6271 例患者的 Meta 分析。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-11 DOI: 10.1007/s40261-024-01401-y
Amira Mohamed Taha, Ahmed Saad Elsaeidy, Sarah A Nada, Sadish Sharma, Mohamed M Ghonaim, Areeba Ahsan, Marina Ramzy Mourid, Khaled Abouelmagd

Background: Iron deficiency is prevalent among heart failure patients and is associated with worse clinical outcomes, including decreased quality of life and functional capacity. This condition often results in a higher incidence of hospitalization and mortality. Iron supplementation, particularly with intravenous ferric carboxymaltose (FCM), has shown potential benefits as an adjunct therapy in heart failure management. This study aims to evaluate the efficacy of FCM in the treatment of patients with heart failure and iron deficiency anemia, with a focus on its impact on mortality and hospitalization rates.

Methods: A comprehensive search was conducted in PubMed, Web of Science, and Scopus databases from their inception until 1st December 2023. Meta-analysis was performed using RevMan 5.4, employing a random-model effect. The results were reported as risk ratios (RRs), standard mean differences (SMDs), and 95 % confidence intervals (CIs).

Results: The meta-analysis included 13 studies with a total of 6271 patients. Ferric carboxymaltose administration resulted in a significant improvement in the 6-minute walk distance (SMD: 1.45; 95 % CI: 0.55, 2.36; p = 0.002), quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (SMD: 1.49; 95 % CI: 0.87, 2.11; p < 0.00001), the rate of first hospitalization for heart failure or cardiovascular death (RR: 0.91; 95 % CI: 0.84, 0.98; p = 0.02). However, FCM did not show a significant impact on the risk of cardiovascular death (RR: 0.90; 95 % CI: 0.77, 1.05; p = 0.17), the need for intervention due to worsening heart failure (RR: 0.41; 95 % CI: 0.04, 4.51; p = 0.47), or all-cause mortality rates (RR: 0.89; 95 % CI: 0.69, 1.16; p = 0.28).

Conclusion: While FCM treatment in patients with heart failure and iron deficiency anemia significantly improves functional capacity and quality of life, it has no notable effect on mortality rates or the likelihood of hospitalization. These findings highlight the need for further research to explore comprehensive treatment strategies that address both the symptomatic and survival aspects of heart failure management in this patient population.

背景:铁缺乏症在心力衰竭患者中很普遍,并与较差的临床结果有关,包括生活质量和功能能力下降。这种情况往往导致更高的住院率和死亡率。铁补充剂,尤其是静脉注射羧甲基铁(FCM)作为心衰治疗的辅助疗法,已显示出潜在的益处。本研究旨在评估 FCM 在治疗心力衰竭合并缺铁性贫血患者中的疗效,重点关注其对死亡率和住院率的影响:方法:在 PubMed、Web of Science 和 Scopus 数据库中进行了全面检索,检索时间从开始到 2023 年 12 月 1 日。使用 RevMan 5.4 进行元分析,采用随机模型效应。结果以风险比(RRs)、标准平均差(SMDs)和95%置信区间(CIs)的形式报告:荟萃分析包括 13 项研究,共涉及 6271 名患者。服用羧甲基铁可显著改善 6 分钟步行距离(SMD:1.45;95 % CI:0.55, 2.36;P = 0.002)、堪萨斯城心肌病问卷(KCCQ)评估的生活质量(SMD:1.49; 95 % CI: 0.87, 2.11; p < 0.00001)、因心力衰竭或心血管死亡首次住院率(RR: 0.91; 95 % CI: 0.84, 0.98; p = 0.02)。然而,FCM 对心血管死亡风险(RR:0.90;95 % CI:0.77,1.05;P = 0.17)、心衰恶化导致的干预需求(RR:0.41;95 % CI:0.04,4.51;P = 0.47)或全因死亡率(RR:0.89;95 % CI:0.69,1.16;P = 0.28)并无显著影响:心力衰竭合并缺铁性贫血患者接受 FCM 治疗后,功能和生活质量均有明显改善,但对死亡率或住院的可能性却没有明显影响。这些发现凸显了进一步研究的必要性,以探索综合治疗策略,从症状和生存两方面治疗心衰患者。
{"title":"Efficacy of Intravenous Ferric Carboxymaltose in Heart Failure Patients with Iron Deficiency Anemia: A Meta-analysis of 6271 Patients.","authors":"Amira Mohamed Taha, Ahmed Saad Elsaeidy, Sarah A Nada, Sadish Sharma, Mohamed M Ghonaim, Areeba Ahsan, Marina Ramzy Mourid, Khaled Abouelmagd","doi":"10.1007/s40261-024-01401-y","DOIUrl":"https://doi.org/10.1007/s40261-024-01401-y","url":null,"abstract":"<p><strong>Background: </strong>Iron deficiency is prevalent among heart failure patients and is associated with worse clinical outcomes, including decreased quality of life and functional capacity. This condition often results in a higher incidence of hospitalization and mortality. Iron supplementation, particularly with intravenous ferric carboxymaltose (FCM), has shown potential benefits as an adjunct therapy in heart failure management. This study aims to evaluate the efficacy of FCM in the treatment of patients with heart failure and iron deficiency anemia, with a focus on its impact on mortality and hospitalization rates.</p><p><strong>Methods: </strong>A comprehensive search was conducted in PubMed, Web of Science, and Scopus databases from their inception until 1st December 2023. Meta-analysis was performed using RevMan 5.4, employing a random-model effect. The results were reported as risk ratios (RRs), standard mean differences (SMDs), and 95 % confidence intervals (CIs).</p><p><strong>Results: </strong>The meta-analysis included 13 studies with a total of 6271 patients. Ferric carboxymaltose administration resulted in a significant improvement in the 6-minute walk distance (SMD: 1.45; 95 % CI: 0.55, 2.36; p = 0.002), quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (SMD: 1.49; 95 % CI: 0.87, 2.11; p < 0.00001), the rate of first hospitalization for heart failure or cardiovascular death (RR: 0.91; 95 % CI: 0.84, 0.98; p = 0.02). However, FCM did not show a significant impact on the risk of cardiovascular death (RR: 0.90; 95 % CI: 0.77, 1.05; p = 0.17), the need for intervention due to worsening heart failure (RR: 0.41; 95 % CI: 0.04, 4.51; p = 0.47), or all-cause mortality rates (RR: 0.89; 95 % CI: 0.69, 1.16; p = 0.28).</p><p><strong>Conclusion: </strong>While FCM treatment in patients with heart failure and iron deficiency anemia significantly improves functional capacity and quality of life, it has no notable effect on mortality rates or the likelihood of hospitalization. These findings highlight the need for further research to explore comprehensive treatment strategies that address both the symptomatic and survival aspects of heart failure management in this patient population.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615206","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
Cost-Effectiveness Analysis of Adjuvant Pertuzumab and Trastuzumab in Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer in Japan. 日本人表皮生长因子受体 2 阳性早期乳腺癌患者使用帕妥珠单抗和曲妥珠单抗辅助治疗的成本效益分析。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-07 DOI: 10.1007/s40261-024-01399-3
Chanon Nusawat, So Sato, Hideaki Watanabe, Takaaki Konishi, Hayato Yamana, Hideo Yasunaga

Background and objective: Human epidermal growth factor receptor 2 (HER2)-positive breast cancer presents considerable treatment challenges owing to its aggressive nature. Global guidelines have endorsed a full year of HER2-targeted therapy for early-stage breast cancer. However, previous cost-effectiveness analyses of dual HER2-targeted therapies have been limited. This study aimed to examine the cost effectiveness of dual HER2-targeted therapy for early-stage breast cancer within the Japanese healthcare system context.

Methods: In the Markov model-based study, the cost effectiveness of dual anti-HER2 therapy, combining pertuzumab and trastuzumab, was assessed in comparison to trastuzumab monotherapy. Patients in whom treatment was initiated at a median age of 51 years were included. The study utilized quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) as comparison units. Subgroup analyses were conducted to explore variations in cost effectiveness, focusing on node-positive and node-negative patients. Both one-way deterministic and broader probabilistic sensitivity analyses using Monte Carlo simulations with 10,000 samples were performed from the Japanese healthcare payers perspective.

Results: Dual HER2-targeted therapy led to 0.17 QALYs increment at an additional cost of $US15,289, resulting in an ICER of $US92,232 per QALY. In the subgroup of node-positive patients, the benefit of the dual HER2-targeted therapy was more pronounced, with an increase of 0.64 QALYs and an ICER of $US24,561 per QALY. Sensitivity analyses revealed the model's susceptibility to changes in the transition probabilities from invasive disease-free survival to death, from invasive disease-free survival to first-line metastatic breast cancer, and to costs associated with pertuzumab. Probabilistic sensitivity analysis suggests that for node-positive patients, dual HER2-targeted therapy may be a cost-effective option.

Conclusions: The economic viability of dual HER2-targeted therapy was most pronounced in patients with node-positive high-risk early breast cancer. This study highlights the potential of dual HER2-targeted therapy as a cost-effective addition for these cases.

背景和目的:人表皮生长因子受体 2(HER2)阳性乳腺癌因其侵袭性而给治疗带来了相当大的挑战。全球指南已批准对早期乳腺癌进行全年的 HER2 靶向治疗。然而,以往对 HER2 双靶向疗法的成本效益分析非常有限。本研究旨在考察日本医疗体系中早期乳腺癌双 HER2 靶向疗法的成本效益:在基于马尔可夫模型的研究中,评估了与曲妥珠单抗单一疗法相比,联合使用百妥珠单抗和曲妥珠单抗的双重抗 HER2 疗法的成本效益。研究纳入了中位年龄为 51 岁、开始接受治疗的患者。研究采用质量调整生命年(QALYs)和增量成本效益比(ICERs)作为比较单位。研究还针对结节阳性和结节阴性患者进行了分组分析,以探讨成本效益的差异。从日本医疗支付方的角度出发,采用蒙特卡罗模拟法对 10,000 个样本进行了单向确定性分析和更广泛的概率敏感性分析:HER2 双靶向治疗可增加 0.17 QALYs,额外费用为 15,289 美元,因此每 QALY 的 ICER 为 92,232 美元。在结节阳性患者亚组中,HER2 双靶向疗法的获益更为显著,可增加 0.64 QALYs,每 QALY 的 ICER 为 24,561 美元。敏感性分析表明,该模型易受从侵袭性无病生存期到死亡、从侵袭性无病生存期到一线转移性乳腺癌以及与培妥珠单抗相关的成本等过渡概率变化的影响。概率敏感性分析表明,对于结节阳性患者,HER2 双靶向治疗可能是一种具有成本效益的选择:结论:HER2 双靶向疗法的经济可行性在结节阳性的高危早期乳腺癌患者中最为明显。这项研究强调了双重HER2靶向疗法作为一种具有成本效益的附加疗法在这些病例中的潜力。
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引用次数: 0
Pharmacokinetic Properties of a Once-Weekly Fixed-Ratio Combination of Insulin Icodec and Semaglutide Compared with Separate Administration of Each Component in Individuals with Type 2 Diabetes Mellitus. 2型糖尿病患者每周一次服用伊科达克胰岛素和赛马鲁肽固定比例复方制剂的药代动力学特性与单独服用每种成分的药代动力学特性的比较。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 Epub Date: 2024-11-03 DOI: 10.1007/s40261-024-01405-8
Lisbet Westergaard, Lene Alifrangis, Stephen T Buckley, Hans Veit Coester, Thomas Klitgaard, Niels R Kristensen, Erica Nishimura, Lea Nørgreen, Thaís M P Rocha, Dorte B Steensgaard, Andreas Vegge, Leona Plum-Mörschel

Background and objective: IcoSema is being developed as a subcutaneous once-weekly fixed-ratio combination of the once-weekly basal insulin icodec and the once-weekly glucagon-like peptide-1 receptor agonist semaglutide. This study investigated the pharmacokinetics of icodec and semaglutide in IcoSema versus separate administration of each component in individuals with type 2 diabetes mellitus (T2DM).

Methods: In a randomised, double-blind, three-period crossover study, 31 individuals with T2DM (18-64 years, body weight 80-120 kg, glycosylated haemoglobin 6.0-8.5%) received single subcutaneous injections of IcoSema (175 U icodec, 0.5 mg semaglutide), icodec (175 U) or semaglutide (0.5 mg) with 6-9 weeks' washout. Pharmacokinetic blood samples were drawn up to 840 h post-dose.

Results: Icodec pharmacokinetics were unaffected by combining icodec with semaglutide. The 90% confidence interval (CI) of IcoSema/icodec was within 0.80-1.25 for total exposure (area under the curve from zero to last quantifiable observation; AUC0-t: ratio [90% CI] 1.06 [1.01; 1.12]) and maximum concentration (Cmax): 1.12 [1.06; 1.18]. Semaglutide AUC0-t was also unaffected by combination with icodec (IcoSema/semaglutide 1.11 [1.05; 1.17]). However, semaglutide Cmax was higher for IcoSema versus semaglutide alone (IcoSema/semaglutide 1.99 [1.84; 2.15]) and occurred earlier for IcoSema (12 versus 84 h). Results of in vitro albumin binding studies and animal pharmacokinetic studies supported that the change in semaglutide absorption pharmacokinetics in IcoSema is owing to competition for albumin binding locally at the injection site with icodec outcompeting semaglutide. IcoSema, icodec and semaglutide were well-tolerated, although more gastrointestinal related adverse events occurred with IcoSema versus icodec or semaglutide alone.

Conclusion: The combination of icodec and semaglutide in IcoSema leads to a higher and earlier maximum semaglutide concentration, which will guide the dose recommendations for IcoSema.

Clinical trial: ClinicalTrials.gov identifier: NCT03789578.

背景和目的IcoSema是每周一次的基础胰岛素icodec和每周一次的胰高血糖素样肽-1受体激动剂semaglutide的皮下固定比例复方制剂。本研究调查了伊科赛马中的icodec和semaglutide在2型糖尿病(T2DM)患者中的药代动力学,以及每种成分单独给药的药代动力学:在一项随机、双盲、三期交叉研究中,31 名 T2DM 患者(18-64 岁,体重 80-120 公斤,糖化血红蛋白 6.0-8.5%)接受了 IcoSema(175 U icodec、0.5 毫克 semaglutide)、icodec(175 U)或 semaglutide(0.5 毫克)的单次皮下注射,并进行了 6-9 周的冲洗。药代动力学血样在服药后840小时内采集:结果:icodec与semaglutide合用不会影响icodec的药代动力学。在总暴露量(从零到最后一次可量化观察的曲线下面积;AUC0-t:比值[90% CI] 1.06 [1.01; 1.12])和最大浓度(Cmax)方面,伊科塞马/伊科代克的 90% 置信区间(CI)在 0.80-1.25 之间:1.12 [1.06; 1.18].塞马鲁肽的AUC0-t也不受与icodec联用的影响(IcoSema/塞马鲁肽:1.11 [1.05; 1.17])。不过,与单独使用塞马鲁肽相比,伊科司马的塞马鲁肽Cmax更高(伊科司马/塞马鲁肽为1.99 [1.84; 2.15]),而且伊科司马的Cmax出现得更早(12小时对84小时)。体外白蛋白结合研究和动物药代动力学研究的结果表明,IcoSema 中塞马鲁肽吸收药代动力学的变化是由于注射部位的白蛋白结合竞争导致的,icodec 优于塞马鲁肽。IcoSema、icodec和semaglutide的耐受性良好,但IcoSema与icodec或单独使用semaglutide相比,发生了更多的胃肠道相关不良事件:结论:在IcoSema中联合使用icodec和semaglutide可提高并提前达到semaglutide的最大浓度,这将为IcoSema的剂量推荐提供指导:临床试验:ClinicalTrials.gov identifier:NCT03789578。
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引用次数: 0
Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study. 多发性硬化症患者使用富马酸双嘧达莫的实际体验:一项前瞻性多中心研究。
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 Epub Date: 2024-10-28 DOI: 10.1007/s40261-024-01397-5
Clara Aguirre, Ana Alonso-Torres, Eduardo Agüera, José Manuel García-Domínguez, Paloma Montero-Escribano, Vicente González-Quintanilla, Lucienne Costa-Frossard, Celia Oreja-Guevara, Virginia Reyes-Garrido, Ana Belén Caminero-Rodríguez, Javier Riancho, Octavio Sánchez, Lucía Forero, Fernando Pérez-Parra, Adrián Ares-Luque, Nieves Téllez, Joaquín Arzalluz-Luque, Federico Iglesias, Virginia Casado-Ruiz, Alberto José Castellano-Vicente, Laura Borrega, Victoria Galán, Luis A Rodríguez de Antonio, Carlos Romero, Raquel García-Rodríguez, Antonio Tomás Cano-Orgaz, José Luis Sánchez-Menoyo, Domingo Pérez-Ruiz, Fuencisla Gutiérrez-Martin, Luis Hernández-Echevarría, Virginia Meca-Lallana

Background: Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment.

Objectives: This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction.

Methods: In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity).

Results: A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity.

Conclusion: This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS.

背景:现有文献和一项实际研究表明,在治疗多发性硬化症(MS)时,富马酸双羟萘胺(DRF)比富马酸二甲酯(DMF)更安全。然而,迄今为止还没有一项真实世界研究对该疗法的疗效进行过深入探讨:本研究旨在阐明 DRF 在真实世界环境中的安全性、耐受性和疗效,利用的数据来自西班牙国家登记处,该登记处登记了 DRF 上市后开始治疗的患者:在这项多中心前瞻性观察研究中,收集了开始接受 DRF 治疗的多发性硬化症患者的数据。研究监测了人口统计学和临床特征、安全性结果(包括不良事件、停药原因和淋巴细胞计数)以及疗效结果(放射学和临床活动):26个神经科共纳入195名多发性硬化症患者,其中以女性为主(79.5%),平均年龄为42.17岁,接受DRF治疗的平均时间为6.3个月。大多数患者(70.3%)未报告不良反应,而胃肠道问题和潮红是最常见的不良反应。大多数患者(84.6%)继续接受 DRF 治疗,耐受性问题是患者中断治疗的主要原因。疗效分析表明,DRF治疗后的复发率较低,大多数患者的残疾状况扩展量表评分稳定或有所改善,放射学评估显示活动性极小:这项综合分析为 DRF 在现实世界中的应用提供了有价值的见解,证实了 DRF 的安全性和耐受性,同时也为 DRF 治疗多发性硬化症的疗效提供了初步证据。
{"title":"Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study.","authors":"Clara Aguirre, Ana Alonso-Torres, Eduardo Agüera, José Manuel García-Domínguez, Paloma Montero-Escribano, Vicente González-Quintanilla, Lucienne Costa-Frossard, Celia Oreja-Guevara, Virginia Reyes-Garrido, Ana Belén Caminero-Rodríguez, Javier Riancho, Octavio Sánchez, Lucía Forero, Fernando Pérez-Parra, Adrián Ares-Luque, Nieves Téllez, Joaquín Arzalluz-Luque, Federico Iglesias, Virginia Casado-Ruiz, Alberto José Castellano-Vicente, Laura Borrega, Victoria Galán, Luis A Rodríguez de Antonio, Carlos Romero, Raquel García-Rodríguez, Antonio Tomás Cano-Orgaz, José Luis Sánchez-Menoyo, Domingo Pérez-Ruiz, Fuencisla Gutiérrez-Martin, Luis Hernández-Echevarría, Virginia Meca-Lallana","doi":"10.1007/s40261-024-01397-5","DOIUrl":"10.1007/s40261-024-01397-5","url":null,"abstract":"<p><strong>Background: </strong>Current literature and a real-world study suggest that diroximel fumarate (DRF) is safer than dimethyl fumarate (DMF) in the treatment of multiple sclerosis (MS). However, no real-world study to date has significantly addressed the efficacy of this treatment.</p><p><strong>Objectives: </strong>This study aims to elucidate the safety, tolerability, and efficacy of DRF in a real-world setting, utilizing data from a Spanish national registry of patients commencing DRF therapy post-market introduction.</p><p><strong>Methods: </strong>In this multicenter, prospective observational study, data were collected from MS patients who initiated DRF treatment. The study monitored demographic and clinical characteristics, safety outcomes (including adverse events, reasons for discontinuation, and lymphocyte counts), and efficacy outcomes (radiological and clinical activity).</p><p><strong>Results: </strong>A total of 195 MS patients across 26 neurological departments were included, predominantly female (79.5%), with a mean age of 42.17 years, and a mean duration of treatment with DRF of 6.3 months. Most patients (70.3%) reported no adverse events, while gastrointestinal issues and flushing were the most common adverse events observed. The majority of patients (84.6%) continued with DRF treatment, with tolerability issues being the primary reason for discontinuation. Efficacy analysis showed low relapse rates post-DRF initiation, with most patients exhibiting stable or improved Expanded Disability Status Scale scores and radiological assessments demonstrating minimal activity.</p><p><strong>Conclusion: </strong>This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS.</p>","PeriodicalId":10402,"journal":{"name":"Clinical Drug Investigation","volume":" ","pages":"829-838"},"PeriodicalIF":2.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521197","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
Pharmacokinetics and Tolerability of the Novel Myeloperoxidase Inhibitor Mitiperstat in Healthy Japanese and Chinese Volunteers. 新型髓过氧化物酶抑制剂米替司他在日本和中国健康志愿者中的药代动力学和耐受性研究
IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 Epub Date: 2024-11-04 DOI: 10.1007/s40261-024-01402-x
Mikael Sunnåker, Chandrali Bhattacharya, Karin Nelander, Malin Aurell, Maria Heijer, Anna Collén, David Han, Julie Holden, Monika Trebski, Pavlo Garkaviy, Hans Ericsson

Background and objective: Mitiperstat (AZD4831) is a novel irreversible oral myeloperoxidase inhibitor in clinical development for heart failure with preserved ejection fraction, metabolic dysfunction-associated steatohepatitis and chronic obstructive pulmonary disease. This study evaluated the pharmacokinetics, safety and tolerability of multiple ascending doses of mitiperstat in healthy male Japanese and Chinese volunteers.

Methods: Three cohorts of eight Japanese participants were randomized to receive once-daily oral doses of mitiperstat 2.5, 5 or 10 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo, per cohort). One cohort of eight Chinese participants was randomized to receive mitiperstat 5 mg or matching placebo for 10 days (six receiving mitiperstat and two receiving placebo).

Results: Mitiperstat was rapidly absorbed, with a time to maximum plasma concentration of 1-2 h. Exposure was dose proportional over the investigated dose range, as assessed by area under the concentration-time curve and maximum and trough plasma concentrations. Steady state was reached within 10 days, and accumulation was observed, consistent with the observed long elimination half-life of mitiperstat (50.2-57.8 h). Except for a few events of maculopapular rash, mitiperstat up to 5 mg was well tolerated in participants of Japanese or Chinese origin.

Conclusions: The pharmacokinetics of mitiperstat were similar among Japanese and Chinese participants. These characteristics were similar to those in a previous multiple ascending-dose study in healthy primarily white and Black/African American volunteers. Therefore, the pharmacokinetics of mitiperstat do not affect dosing regimens in these different populations.

Trial registration: NCT04232345 (03/01/2020).

背景和目的米替哌司他(AZD4831)是一种新型不可逆口服髓过氧化物酶抑制剂,目前正处于临床开发阶段,可用于治疗射血分数保留型心力衰竭、代谢功能障碍相关性脂肪性肝炎和慢性阻塞性肺病。本研究评估了日本和中国健康男性志愿者服用多个升剂量米替哌司坦的药代动力学、安全性和耐受性:三个队列的八名日本参与者被随机分配接受每日一次口服剂量为 2.5、5 或 10 毫克的米替司特或相应的安慰剂,为期 10 天(每个队列六人接受米替司特,两人接受安慰剂)。一个由8名中国参与者组成的队列随机接受米替哌司坦5毫克或相应安慰剂,为期10天(6人接受米替哌司坦,2人接受安慰剂):米哌司坦吸收迅速,血浆浓度达到最大值的时间为1-2小时。在研究的剂量范围内,米哌司坦的暴露与剂量成正比,浓度-时间曲线下面积以及血浆浓度的最大值和谷值均可评估这一点。米替哌司坦在 10 天内达到稳定状态,并出现蓄积现象,这与观察到的米替哌司坦的长消除半衰期(50.2-57.8 小时)一致。除了少数斑丘疹外,日本或中国血统的参试者对5毫克以下的米替司他耐受性良好:结论:日本人和中国人服用米替司他的药代动力学相似。结论:日本和中国参试者的药代动力学相似,这些特征与之前在主要为白人和黑人/非洲裔美国人的健康志愿者中进行的多次递增剂量研究相似。因此,米替哌司坦的药代动力学不会影响这些不同人群的给药方案:NCT04232345 (03/01/2020).
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引用次数: 0
Cost-Effectiveness of Empagliflozin (JARDIANCE®) in the Treatment of Patients with Chronic Kidney Disease in France, Based on the EMPA-KIDNEY Clinical Trial. 基于 EMPA-KIDNEY 临床试验的 Empagliflozin (JARDIANCE®) 治疗法国慢性肾病患者的成本效益。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 Epub Date: 2024-10-24 DOI: 10.1007/s40261-024-01398-4
Harinala Groyer, Romain Supiot, Jean Tardu, Nicolas Virely, Marine Sivignon, Denis San, Pierre Lévy, Anastasia Ustyugova, Ziad A Massy

Background and objective: The efficacy and safety of empagliflozin in the treatment of chronic kidney disease (CKD) were demonstrated in the EMPA-KIDNEY trial, which showed a 28% reduction in combined risks of kidney disease or death from cardiovascular causes (hazard ratio, 0.72; 95% confidence interval, 0.64-0.82; p < 0.001) compared with placebo. Based on these results, the present study aimed to assess the cost-effectiveness of empagliflozin + standard of care (SoC) compared with SoC alone in the treatment of CKD in France.

Methods: A Markov state microsimulation model was adapted to compare the health and economic outcomes in France, considering a healthcare system perspective, in patients treated with empagliflozin in addition to SoC versus patients treated with SoC alone. The model simulated the intention-to-treat population of the trial, transitioning between 18 mutually exclusive and collectively exhaustive health states defined based on the Kidney Disease: Improving Global Outcomes classification. For each arm, the model estimated (over a 25-year time horizon) the number of events and deaths, and the costs associated with these events, to calculate the incremental cost-effectiveness ratio. The resources used were derived using French authorities reports, literature, and French CKD guidelines. Both economic and health outcomes were discounted at a 2.5% annual rate according to French guidelines.

Results: The model predicted that using empagliflozin + SoC to treat patients with CKD would prevent CKD-related complications and deaths associated with a cardiovascular event or all-cause deaths while in kidney replacement therapy, resulting on average in a discounted gain of 1.29 years in overall survival (9.48 years vs. 8.19 with SoC alone). Empagliflozin costs (treatment, events, and disease management) were completely offset by the cost savings from avoided kidney failure events. Overall, empagliflozin + SoC would be more effective and less costly than SoC alone and would therefore be the dominant treatment strategy. The sensitivity analyses conducted support the results' robustness in showing the dominance of empagliflozin + SoC over SoC alone.

Conclusions: The base-case results indicate that empagliflozin + SoC is a dominant strategy compared with the current SoC for the management of CKD in France. Empagliflozin + SoC would have a positive impact on patients with CKD by slowing CKD progression and leading to the prevention of kidney failure events on top of all-stages CKD complications.

背景和目的:EMPA-KIDNEY试验显示,与安慰剂相比,empagliflozin治疗慢性肾脏病(CKD)的疗效和安全性降低了28%(危险比为0.72;95%置信区间为0.64-0.82;P < 0.001)。基于这些结果,本研究旨在评估在法国治疗慢性肾脏病时,empagliflozin+标准疗法(SoC)与单独使用标准疗法相比的成本效益:采用马尔可夫状态微观模拟模型,从医疗保健系统的角度出发,比较在法国接受empagliflozin+SoC治疗的患者与仅接受SoC治疗的患者的健康和经济结果。该模型模拟了试验中的意向治疗人群,在根据肾脏疾病分类界定的 18 种相互排斥且共同详尽的健康状态之间转换:改善全球疗效》分类法定义的 18 种相互排斥且共同详尽的健康状态之间转换。对于每个治疗组,该模型(在 25 年的时间跨度内)估算了事件数和死亡数,以及与这些事件相关的成本,从而计算出增量成本效益比。所使用的资源来自法国权威报告、文献和法国慢性肾脏病指南。根据法国指南,经济和健康结果均按2.5%的年贴现率进行贴现:该模型预测,使用恩格列净+SoC治疗CKD患者可预防CKD相关并发症、心血管事件相关死亡或肾脏替代治疗期间的全因死亡,平均可使总生存期折现延长1.29年(9.48年与单独使用SoC的8.19年相比)。因避免肾衰竭事件而节省的成本完全抵消了恩格列净的成本(治疗、事件和疾病管理)。总体而言,与单独使用 SoC 相比,恩格列净 + SoC 的疗效更好、成本更低,因此是最主要的治疗策略。所进行的敏感性分析支持了结果的稳健性,显示了恩格列净+SoC比单独使用SoC更有优势:基础研究结果表明,在法国,与目前的SoC相比,empagliflozin + SoC是治疗CKD的主要策略。Empagliflozin + SoC 将对慢性肾功能衰竭患者产生积极影响,因为它能减缓慢性肾功能衰竭的进展,并在所有阶段的慢性肾功能衰竭并发症基础上预防肾衰竭事件的发生。
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引用次数: 0
A Pilot Study of the Effectiveness of a Short Course of Rifaximin 2200 mg/day on Abdominal Symptoms and its Effects on Quality of Life in Patients with Moderate to Severe Diarrhea-Predominant Irritable Bowel Syndrome. 中度至重度腹泻为主的肠易激综合征患者短期服用利福昔明 2200 毫克/天对腹部症状的疗效及其对生活质量的影响的试验性研究》。
IF 4.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1007/s40261-024-01403-w
Marjan Mokhtare, Maryam Fathi, Amir M Sadeghian, Mohammad-Javad Sotoudeheian, Abolfazl Namazi

Background and objective: Rifaximin is used to treat diarrhea-predominant irritable bowel syndrome (IBS-D). However, determining the most effective regimen remains a challenge. This study aimed to evaluate the effectiveness and safety of a 10-day high-dose course of rifaximin (2200 mg/day) and its effects on both abdominal symptoms and quality of life (QOL) in patients with IBS-D.

Method: Adult patients with moderate to severe IBS-D (Rome IV) and fecal urgency and bloating were prescribed rifaximin 1100 mg twice daily for 10 days. Demographic information, the IBS Symptom Severity Index (IBS-SSI) score (using a 7-point Likert scale), and Bristol Stool Scale (BSS) score were recorded at baseline, day 10, and 4 weeks after treatment cessation. IBS Symptom Severity Score (IBS-SSS) and IBS-QOL scores were recorded at baseline and day 10. Any drug adverse effects were recorded.

Results: In total, 39 patients completed the study. Average scores for all abdominal symptoms and BSS showed significant improvement at day 10 and 4 weeks after treatment cessation (all p < 0.001). A significant improvement was seen in IBS-SSS and overall IBS-QOL score at day 10 (p < 0.001), with the highest improvement (31%) in interference with activity. Moreover, composite improvement rates were 38.64% for all abdominal symptoms, together with BSS < 5, bi-composite (66.67% for abdominal pain + bloating; 61.54% for abdominal pain + urgency), and 56.41% for tri-composite (abdominal pain + bloating + urgency) symptoms. Notably, no serious adverse effects were reported, and the adherence rate was 94.9%.

Conclusions: Abdominal symptoms and overall QOL, especially in social and work dimensions, significantly improved in patients with moderate to severe IBS-D following a regimen of rifaximin 2200 mg/day, which was well tolerated.

背景和目的:利福昔明用于治疗以腹泻为主的肠易激综合征(IBS-D)。然而,确定最有效的治疗方案仍是一项挑战。本研究旨在评估利福昔明 10 天大剂量疗程(2200 毫克/天)的有效性、安全性及其对 IBS-D 患者腹部症状和生活质量(QOL)的影响:方法:对患有中度至重度肠易激综合征(IBS-D)(罗马Ⅳ型)、便急和腹胀的成人患者处方利福昔明,剂量为 1100 毫克,每天两次,疗程为 10 天。在基线、第 10 天和停止治疗 4 周后记录人口统计学信息、肠易激综合征症状严重程度指数 (IBS-SSI) 评分(采用 7 点李克特量表)和布里斯托粪便量表 (BSS) 评分。在基线和第 10 天记录肠易激综合征症状严重程度评分(IBS-SSS)和肠易激综合征-QOL 评分。记录任何药物不良反应:共有 39 名患者完成了研究。所有腹部症状和 BSS 的平均得分在第 10 天和停止治疗 4 周后均有明显改善(均为 p 结论:所有腹部症状和总体 QOL 均有明显改善:中度至重度肠易激综合征(IBS-D)患者在服用利福昔明 2200 毫克/天治疗方案后,腹部症状和总体 QOL(尤其是社交和工作方面)明显改善,且耐受性良好。
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Clinical Drug Investigation
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