Abstract:
PURPOSE:The goal of this study was to assess the long-term safety and efficacy of mepolizumab in patients with the most severe eosinophilic asthma. METHODS:This multicenter, open-label, long-term, Phase IIIb study (COSMEX [COSMOS Extension]; 201312/NCT02135692) enrolled patients from the 52-week, open-label extension study COSMOS (A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects) that previously enrolled patients from the double-blinded, placebo-controlled Phase III studies MENSA (Mepolizumab as Adjunctive Therapy in Patients with Severe Asthma) and SIRIUS (Steroid Reduction with Mepolizumab Study). To enter COSMEX, patients had to have life-threatening/seriously debilitating asthma before entering MENSA or SIRIUS and to have completed these previous studies with demonstrated improvement while receiving mepolizumab. In COSMEX, patients received mepolizumab 100 mg subcutaneously every 4 weeks as add-on therapy for up to 172 weeks. Primary endpoints were adverse event frequency and exacerbation rate per year; also assessed were forced expiratory volume in 1 s, Asthma Control Questionnaire-5 score, and daily oral corticosteroid (OCS) use. FINDINGS:Of the 340 patients enrolled, 339 received mepolizumab; median treatment duration within this extension study was 2.2 years, equating to 718 patient-years of additional exposure. No new safety signals were identified. Patients receiving mepolizumab throughout this study and previous studies had lasting reductions in exacerbation rate and daily OCS use and improvements in forced expiratory volume in 1 s and Asthma Control Questionnaire-5 score. In COSMEX, the on-treatment exacerbation rate (95% CI) was 0.93 (0.81-1.06) event/year for clinically significant exacerbations, 0.13 (0.10-0.18) event/year for exacerbations requiring hospitalization/emergency department visit, and 0.07 (0.05-0.10) event/year for exacerbations requiring hospitalization. In patients requiring systemic/oral corticosteroids with ≥128 weeks of continuous enrollment across SIRIUS, COSMOS, and COSMEX, mepolizumab maintained the median daily OCS dose at 1.3-2.8 mg during COSMEX, with additional patients no longer requiring OCS after extended mepolizumab treatment. IMPLICATIONS:This study indicates that long-term mepolizumab treatment is well tolerated and associated with sustained clinical benefits in patients with severe eosinophilic asthma. ClinicalTrials.gov identifier: NCT02135692.
journal_name
Clin Therjournal_title
Clinical therapeuticsauthors
Khurana S,Brusselle GG,Bel EH,FitzGerald JM,Masoli M,Korn S,Kato M,Albers FC,Bradford ES,Gilson MJ,Price RG,Humbert Mdoi
10.1016/j.clinthera.2019.07.007subject
Has Abstractpub_date
2019-10-01 00:00:00pages
2041-2056.e5issue
10eissn
0149-2918issn
1879-114Xpii
S0149-2918(19)30350-9journal_volume
41pub_type
杂志文章,多中心研究abstract:BACKGROUND:Patients' preferences for medications may be important in determining their compliance with therapy, particularly in the case of an asymptomatic chronic disease such as osteoporosis. Although preferences for certain attributes of osteoporosis medications, including dosing frequency and tolerability, can be e...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(07)80087-7
更新日期:2007-03-01 00:00:00
abstract:BACKGROUND:Pharmacokinetic/pharmacodynamic (PK/PD) optimization of antibiotic therapy has been shown to improve outcomes in several antibiotic classes. Despite the frequent use of beta-lactams, clinical data in humans remain limited. OBJECTIVE:This study evaluated the relationship between serum pharmacokinetics, pharm...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(01)80103-x
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Rates of patient adherence (compliance) to pharmacotherapy range from <5% to >90%. Negative determinants include multiple daily dosing (MDD), chronic duration, and asymptomatic disease. Reports suggest that once-daily (QD) dosing may improve adherence, but their findings are inconclusive. OBJECTIVE:The purp...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析
doi:10.1016/s0149-2918(02)85026-3
更新日期:2002-02-01 00:00:00
abstract::A benzothiazepine derivative, CRD-401, was administered orally in a dosage of 60 to 120 mg/day to 14 patients with various renal diseases. The systolic pressure was lowered slightly in some cases after administration of CRD-401. Urine volume and urinary excretion of electrolytes were increased by the drug in most pati...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1981-01-01 00:00:00
abstract::Enoxacin 400 mg twice daily was given orally to 40 patients who had Salmonella typhi- or Salmonella paratyphi-positive blood or bone marrow cultures. One patient was switched to parenteral therapy within 48 hours of study enrollment, but the remaining 39 patients were given enoxacin for 10 to 14 days. All 39 patients ...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
abstract::The monomeric insulin analogue insulin lispro (Lys B28, Pro B29) is a rapid-acting insulin with a shorter duration of activity than human regular insulin. This compound has the advantage of reducing early postprandial hyperglycemia and the accompanying late hypoglycemia, thereby improving overall blood glucose control...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/s0149-2918(98)80040-4
更新日期:1998-01-01 00:00:00
abstract:OBJECTIVE:The aim of this study was to describe the pharmacokinetics of 3 different single doses of fulvestrant-a new estrogen receptor (ER) antagonist that downregulates the ER with no known agonist effects-administered as a prolonged-release IM formulation. METHODS:Pharmacokinetic data were obtained in a randomized,...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0149-2918(03)80131-5
更新日期:2003-05-01 00:00:00
abstract:BACKGROUND:Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). OBJECTIVE:The objective of this study was to evaluate the cost-effect...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2013.12.011
更新日期:2014-02-01 00:00:00
abstract::The objective of this study was to assess a weight-based heparin (WBH) nomogram (80-U/kg bolus, 18-U/kg-per-hour initial infusion) and determine its clinical performance and impact on resource utilization. All patients treated with heparin for venous thromboembolism or unstable angina during a 15-week study period wer...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/s0149-2918(98)80133-1
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND:Hypertension usually clusters with other cardiovascular risk factors; however, it has not been reported whether hypertension treatment has an impact on the awareness and treatment of other cardiovascular risk factors such as diabetes mellitus and hypercholesterolemia. OBJECTIVE:To analyze the effect of hype...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.05.006
更新日期:2012-07-01 00:00:00
abstract::General health-status questionnaires such as the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) are frequently used to measure health-related quality of life. The SF-36, in its current form, cannot be used to measure individuals' utilities or preferences for their health state. Recently, several inves...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/S0149-2918(00)86747-8
更新日期:1999-11-01 00:00:00
abstract::Forty patients with symptoms of rheumatoid arthritis were treated with daily injections of 100 micrograms of human leukocyte interferon or saline placebo. Twenty patients received the interferon for nine weeks and were then switched to placebo for nine weeks, and 20 patients were started on placebo and were then switc...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1986-01-01 00:00:00
abstract:INTRODUCTION:Hemorrhagic cystitis is a potentially life-threatening complication in patients receiving cancer therapy. This urologic emergency is commonly associated with the chemotherapeutic use of oxazaphosphorine alkylating agents. This report describes a case of hemorrhagic cystitis associated with dacarbazine trea...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2007.06.004
更新日期:2007-06-01 00:00:00
abstract:PURPOSE:Intensive blood pressure (BP) lowering is important for the treatment of hypertension; however, it has been a challenge to achieve target BP in many patients. The purpose of this study was to explore the optimal dosage of a fixed-dose combination of candesartan cilexetil (CAN) and amlodipine besylate (AML), by ...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.clinthera.2017.06.014
更新日期:2017-08-01 00:00:00
abstract:BACKGROUND:Conflicting results using the combination of ezetimibe and statins to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS) have been reported. OBJECTIVE:The aim of this work was to assess the effectiveness of ezetimibe coadministered with statins in reducing cardiovascular...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2011.08.002
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:In 2002, fixed-dose combination therapy (FDCT) with rosiglitazone maleate plus metformin hydrochloride became available for the treatment of type 2 diabetes mellitus (DM-2) in subjects whose disease was uncontrolled on monotherapy with metformin or a thiazolidinedione. FDCT allows a reduced pill burden and a...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2004.12.018
更新日期:2004-12-01 00:00:00
abstract:PURPOSE:Nemonoxacin is a novel C-8-methoxy nonfluorinated quinolone that has been approved for the treatment of community-acquired pneumonia (CAP) in adults. The goals of this study were to evaluate the pharmacokinetic (PK) and population PK parameters of nemonoxacin and to provide the appropriate dose adjustment recom...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:10.1016/j.clinthera.2019.01.015
更新日期:2019-03-01 00:00:00
abstract:BACKGROUND:The therapeutic effectiveness of Echinacea in the treatment and the prevention of colds has been debated. Studies of naturally occurring colds are hampered by variability in time from onset of symptoms to treatment and by heterogeneity in trial design. Experimental infection studies allow for the standardiza...
journal_title:Clinical therapeutics
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.clinthera.2006.02.001
更新日期:2006-02-01 00:00:00
abstract::Lipid metabolism, platelet function, and blood coagulability were evaluated in 20 patients with diabetes mellitus and stable fasting blood sugar levels before, during, and after treatment with the pancreatic enzyme elastase for 16 weeks. Serum high-density lipoprotein cholesterol levels increased from 46.9 mg/dl befor...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00
abstract:PURPOSE:Multidrug-resistant bacterial pathogens are becoming a significant problem worldwide. Acinetobacter baumannii and Pseudomonas aeruginosa are problematic multidrug-resistant pathogens. This multicenter study in Vietnam determined the level of resistance to antimicrobial agents used to treat A baumannii and P aer...
journal_title:Clinical therapeutics
pub_type: 杂志文章,多中心研究
doi:10.1016/j.clinthera.2016.07.172
更新日期:2016-09-01 00:00:00
abstract:BACKGROUND:Moxifloxacin is a fluoroquinolone antimicrobial agent with proven efficacy against community-acquired respiratory pathogens. Common adverse effects associated with its use include gastro-intestinal symptoms, but nephrotoxicity has not yet been reported to the manufacturer or in the literature (based on a MED...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2005.08.008
更新日期:2005-08-01 00:00:00
abstract::Immediate complications of trauma and shock include right heart failure, acute respiratory distress syndrome, coagulopathy, brain edema, small bowel dysfunction, renal failure, and immune dysfunction. Nosocomial infections are also common in trauma patients. These infections are the combined result of a compromised ho...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:
更新日期:1990-01-01 00:00:00
abstract:BACKGROUND:The prevalence of gout has been increasing. Serum uric acid (sUA) levels ≥6 mg/dL have been associated with high morbidity and increased health care utilization. OBJECTIVE:To assess the costs and patterns of health care resource utilization for patients with gout, categorized into 3 cohorts based on sUA lev...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2012.01.020
更新日期:2012-03-01 00:00:00
abstract:BACKGROUND:Breast cancer surgery performed with the patient under general anesthesia has been associated with a relatively high incidence of postoperative nausea and vomiting (PONV). Between 60% and 80% of patients who undergo mastectomy (with axillary dissection) experience PONV. We previously reported that propofol a...
journal_title:Clinical therapeutics
pub_type: 杂志文章,随机对照试验,收录出版
doi:10.1016/j.clinthera.2008.11.011
更新日期:2008-11-01 00:00:00
abstract::The United States maternal mortality rate has been rising for many years putting the US out of step with peer countries. There are many complex reasons for the rise in maternal deaths and recent data has demonstrated that there is a disproportionate risk for women of color. This article provides an overview of current...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/j.clinthera.2020.01.015
更新日期:2020-03-01 00:00:00
abstract::This tenth anniversary review/update of fluoxetine concentrates on the past 5 years of its clinical application. The mechanism of action of fluoxetine; its metabolism; its efficacy in patients with various diagnostic subgroups of depression, patients with coincident medical disease, children and adolescents with depre...
journal_title:Clinical therapeutics
pub_type: 杂志文章,评审
doi:10.1016/s0149-2918(97)80066-5
更新日期:1997-09-01 00:00:00
abstract::Twenty-five patients with typhoid fever, who were resistant to amoxicillin and chloramphenicol, were successfully treated with ofloxacin. Ofloxacin was administered at a dosage of 200 mg three times daily for 7 to 10 days. In a few seriously ill patients, a dosage of 400 mg three times daily for 3 days, followed by 20...
journal_title:Clinical therapeutics
pub_type: 临床试验,杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::An open clinical trial with prifinium bromide, an anticholinergic agent, was carried out in 21 patients with irritable bowel syndrome showing clear psychosomatic characteristics. The clinical efficacy was evaluated by comparing the symptomatic severity before, during, and after treatment with prifinium bromide, 90 mg/...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Tetanus-diphtheria-acellular pertussis (Tdap) was licensed in the United States in 2005 to be given in place of tetanus-diphtheria (Td) for single use in adolescents. OBJECTIVES:This analysis was conducted to determine vaccination coverage with Td and Tdap among adolescents in the United States aged 13 to 1...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2010.07.016
更新日期:2010-08-01 00:00:00
abstract:PURPOSE:Levodopa (LD) is the most effective oral pharmacotherapy for the management of motor symptoms in Parkinson's disease. However, LD use is complicated by a progressive shortening of the duration of efficacy of a dose, resulting in episodes of inadequate responsiveness, or OFF periods. OFF periods may also occur u...
journal_title:Clinical therapeutics
pub_type: 杂志文章
doi:10.1016/j.clinthera.2020.04.004
更新日期:2020-06-01 00:00:00