MP29-02 for the treatment of seasonal allergic rhinitis: a review of clinical pharmacology,efficacy and safety

This review presents the pharmacology, clinical efficacy and safety of MP29-02 (Dymista®), a unique product for the treatment of allergic rhinitis. Allergic rhinitis is often thought of more as a nuisance than a meaningful medical condition, and the health impact of allergic rhinitis can easily be underestimated. As a result, allergic rhinitis can be undertreated, expectations for relief may not be met, and patients may be left dissatisfied and non-compliant with their medications. MP29-02 is the only currently available allergic rhinitis medication to provide potent early-phase histamine-receptor blocking and long-term anti-inflammatory effects in a single intranasal formulation and delivery system that represents an advance in the therapy of allergic rhinitis, in particular for patients with moderate-to-severe disease.     

吸入沙美特罗/氟替卡松或福莫特罗/布地奈德对支气管哮喘慢性持续期的疗效评价

目的 观察吸入沙美特罗/氟替卡松和福莫特罗/布地奈德对支气管哮喘慢性持续期的疗效.方法 将120例中度支气管哮喘慢性持续期的患者随机分为两组,一组吸入沙美特罗/氟替卡松(50/250),250 μg/次,2次/d,另一组吸入福莫特罗/布地奈德,(4.5/160),160 μg/次,2次/d.评价3个月、6个月内的急性发作次数、夜间发作次数、使用短效β2受体激动剂的次数和哮喘控制调查表评分.结果 治疗3月的沙美特罗组急性发作次数、使用短效β2受体激动剂的次数和哮喘控制调查表评分多于布地奈德组,夜间发作次数少于布地奈德组,但差异没有统计学意义;治疗6月时沙美特罗组急性发作次数、夜间发作次数、使用短效β2受体激动剂的次数和哮喘控制调查表评分均少于布地奈德组,但差异仍没有统计学意义.结论 中度支气管哮喘慢性持续期的患者吸入沙美特罗/氟替卡松或福莫特罗/布地奈德干粉剂均能取得同样的哮喘控制.     

沙美特罗替卡松粉剂吸入治疗70岁以上中、重度AECOPD临床疗效观察

目的 观察沙美特罗替卡松粉剂(舒利迭)吸入用于治疗70岁以上中重度慢性阻塞性肺疾病急性加重期(AECOPD)的疗效.方法 将108例70岁以上中、重度AECOPD患者随机分为沙美特罗/替卡松粉剂吸入组、硫酸沙丁胺醇气雾剂吸入组,对两组治疗前后的FEV1、FEV1/FVC、FEV1占预计值百分比及临床症状改善情况进行比较.结果 使用舒利迭组患者在治疗早期肺功能即有明显改善,随着使用时间延长,肺功能改善得到逐渐提高.使用硫酸沙丁胺醇组,治疗初期,临床症状迅速改善,随着治疗时间延长,疗效有所下降,肺功能无明显改善.结论 舒利迭治疗70岁以上中、重度AECOPD,临床改善明显,能持续改善患者的肺功能.     

噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病急性加重期伴呼吸衰竭的临床研究

目的观察噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗慢性阻塞性肺疾病(COPD)急性加重期伴呼吸衰竭的临床疗效及安全性。方法将76例COPD急性加重期伴呼吸衰竭患者随机分为对照组38例和试验组38例。对照组予以常规治疗配合呼吸机辅助通气治疗;试验组在对照组治疗的基础上,予以沙美特罗替卡松粉吸入剂每次1吸,bid,吸入治疗+噻托溴铵粉雾剂每次18μg,qd,吸入治疗。2组患者均治疗2周。比较2组患者的临床疗效、动脉血气指标、降钙素原和免疫功能,以及药物不良反应的发生情况。结果治疗后,试验组和对照组的总有效率分别为92.11%(35例/38例)和73.68%(28例/38例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的动脉血氧分压分别为(86.35±7.04)和(77.49±6.85)mm Hg,氧合指数分别为(310.89±29.87)和(281.34±27.53)mm Hg,降钙素原分别为(1.42±0.54)和(1.93±0.61)ng·m L^-1,肿瘤坏死因子-α分别为(275.49±48.62)和(310.05±54.73)ng·L^-1,白细胞介素-8分别为(312.62±75.64)和(389.75±78.76)pg·m L^-1,超敏C-反应蛋白分别为(4.73±2.45)和(8.34±2.53)mg·L^-1,差异均有统计学意义(均P<0.05)。2组患者治疗期间均未发生药物不良反应。结论噻托溴铵粉雾剂联合沙美特罗替卡松粉吸入剂治疗COPD急性加重期伴呼吸衰竭的临床疗效确切,其能显著降低患者的降钙素原水平,改善患者的血气指标和免疫功能,且安全性较好。     

A repeat-dose thorough QT study of inhaled fluticasone furoate/vilanterol combination in healthy subjects

AIMS

This study was designed as a thorough QT (TQT) study to evaluate the effects of fluticasone furoate(FF)/vilanterol (VI) in healthy subjects. Supportive data from a TQT study conducted with FF are also presented.

METHODS

This was a randomized, placebo-and positive-controlled, double-dummy, double-blind, four-way crossover study, in which healthy subjects (n = 85) were randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100 μg) or placebo or single-dose oral moxifloxacin (single-blind, 400 mg). In the supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF(4000 μg), oral moxifloxacin (400 mg) or placebo.

RESULTS

There was a lack of effect of FF/VI (200/25 μg) on QTcF (Fridericia''s correction); all time-matched mean differences from baseline relative to placebo (0–24 h) were <5 ms, with upper 90% confidence intervals (CI) of <10 ms. At 800/100 μg, FF/VI had no significant clinicaleffect on QTcF except at 30 min postdose when the 90% CI was >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually corrected) was observed at either strength of FF/VI, with mean time-matched treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0–24 h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time-matched mean differences from baseline relative toplacebo of >10 ms (1–8 h postdose).

CONCLUSIONS

Repeat once-daily dosing of FF/VI (200/25 μg), which is the highest therapeutic strength used in phase III studies, is not associated with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI (800/100 μg) demonstrated a small transient effect on QTcF but not on QTci.     

沙美特罗替卡松治疗中重度支气管哮喘患者的疗效观察

目的观察沙美特罗替卡松治疗中重度支气管哮喘患者的临床疗效。方法 78例中重度支气管哮喘患者随机分为2组,对照组（n=38例）采用常规方法治疗;观察组（n=40例）采用沙美特罗替卡松治疗,2组疗程均为2周。比较2组治疗总有效率及肺功能指标变化情况。结果观察组治疗总有效率（82.5%）明显高于对照组（68.4%）（P〈0.05）;2组治疗后FEV1和FEV1/FVC肺功能情况均明显缓解（P〈0.05）,而观察组改善更为显著（P〈0.05）。结论沙美特罗替卡松治疗中重度支气管哮喘可明显改善临床症状,提高肺功能,值得临床推广应用。     

羧甲司坦联合沙美特罗替卡松气雾剂治疗稳定期D组慢性阻塞性肺疾病的疗效观察

目的：探讨羧甲司坦联合沙美特罗替卡松气雾剂治疗稳定期D组慢性阻塞性肺疾病（COPD）患者的临床疗效。方法选取2011年8月—2013年6月就诊于天津市第四中心医院处于稳定期D组COPD患者96例,随机分为治疗组（50例）和对照组（46例）。对照组在常规治疗基础上吸入沙美特罗替卡松气雾剂,1揿/次,2次/d。治疗组在对照组治疗的基础上口服羧甲司坦口服溶液10 mL/次,3次/d。两组均连续治疗48周。观察两组患者治疗前,治疗8、24、48周运动耐量、呼吸困难指数（mMRC）及肺功能的变化,同时观察两组患者治疗过程中急性加重次数。结果两组患者6 min 步行距离（6MWD）在治疗8、24、48周后均较治疗前显著增加,mMRC均较治疗前有所降低,治疗前后差异有统计学意义（P＜0.05）;治疗24、48周治疗组6MWD显著长于对照组,mMRC显著低于对照组,两组比较差异有统计学意义（P＜0.05）。两组患者在治疗24、48周第1秒用力呼气容积（FEV1）、FEV1占预计值百分比（FEV1/pred%）均较治疗前有所增加,治疗前后差异有统计学意义（P＜0.05）;治疗24、48周治疗组患者FEV1、FEV1/pred%显著高于对照组,两组比较差异有统计学意义（P＜0.05）。结论羧甲司坦联合沙美特罗替卡松气雾剂治疗稳定期D组COPD患者具有较好的临床疗效,可增加患者的运动耐力,改善呼吸困难症状和肺功能,值得临床推广应用。     

A One-Week Dose-Ranging Study of Inhaled Salmeterol in Children with Asthma

This was a 1-week study evaluating the safety and efficacy of two dosage regimens of salmeterol in children with asthma. A total of 243 children, aged 4-11 years, with mild-to-moderate asthma were enrolled in a randomized, double-blind, placebo-controlled, parallel-group, multicenter study evaluating salmeterol xinafoate 21 μg and 42 μg administered via metered-dose inhaler (MDI) twice daily for 1 week. Patients were allowed to use albuterol MDI as needed for relief of acute symptoms. Inhaled corticosteroids and/or cromolyn at fixed dosages could be continued during the study, but theophylline and oral β-agonists were not allowed. Twelve-hour serial spirometry (for patients aged 6-11 years) and serial peak expiratory flow rate (PEFR) (all patients) were performed on days 1 and 8 of treatment; morning and evening PEFR were recorded each day prior to inhalation of the study drug. Safety was assessed by monitoring adverse events, clinical laboratory values, vita signs, electrocardiogram (ECC), and 24-hr ECG (Holter) monitoring. Both the 21 -μg and 42-μg doses of salmeterol produced significantly greater bronchodilation, as measured by 12-hr serial forced expiratory volume in 1 sec (FEV₁) (p ≤ 0.02) and PEFR (p ≤ 0.001), than did placebo on days 1 and 8. A small dose-response was observed, with the 42-μg dosage producing consistently higher serial FEV₁and PEFR than did the 21 -μg dosage, although the differences were not statistically significant. Morning and evening PEFR increased significantly (p ≤ 0.008) with both dosages of salmeterol compared with placebo. Twelve patients (5%) experienced potentially drug-related adverse events, with headache (4% in each salmeterol group) being the most common. There were no clinically significant changes in heart rate as measured by Holter monitoring, ECCs, vital signs, or clinical laboratory values following treatment with either dose of salmeterol. Salmeterol 21 μg or 42 μg twice daily was effective in producing bronchodilation in children aged 4-11 years, and both dosages had good safety profiles. Patients treated with salmeterol 42 μg twice daily showed a trend toward greater improvement in asthma control compared with those who received salmeterol 21 μg.     

糠酸氟替卡松/维兰特罗复方剂治疗哮喘疗效与耐受性的Meta分析

目的 比较糠酸氟替卡松/维兰特罗复方剂（FF/VI）与吸入型糖皮质激素单药或联合长效β₂受体激动剂治疗哮喘患者的疗效与耐受性差异。方法 计算机检索CNKI、PubMed、Embase、Cochrane Library等数据库,纳入随机对照试验,采用Cochrane系统评价方法进行评价。结果 共纳入10个研究,共9 811例患者。在疗效上,FF/VI组与对照组相比,提高患者的1秒用力呼气量谷值[WMD=0.09,95% CI（0.05,0.13）,P=0.000]和哮喘控制测试评分[WMD=0.63,95% CI（0.24,1.03）,P=0.002]。在耐受性方面,FF/VI组与对照组相比不增加患者发生与治疗相关不良反应事件风险[RR=1.15,95% CI（0.98,1.36）,P=0.000]。结论 用FF/VI治疗哮喘在疗效方面具有优势,且具有良好的耐受性。其每日1次的用药频次可提高患者依从性,值得推荐使用。     

联合吸入噻托溴铵和沙美特罗/氟替卡松对稳定期慢性阻塞性肺疾病患者疗效的Meta分析

目的 系统评价联合吸入噻托溴铵和沙美特罗/氟替卡松对慢性阻塞性肺病（COPD）稳定期患者治疗作用.方法 计算机检索Pubmed、维普（VIP）、万方数据库、中国知网和中国生物医学文献数据库（CBM）中关于联合吸入噻托溴铵和沙美特罗/氟替卡松治疗稳定期慢性阻塞性肺疾病的随机对照试验,检索时限为建库至2013年6月.由研究者根据GRADE系统推荐分级方法,对纳入文献进行严格质量评价,对符合质量标准的文献进行Meta分析.统计学分析采用Review Manager 5.1和GRADEprofiler 3.6软件.结果 共纳入15篇研究,Meta分析结果显示：联合吸入沙美特罗/氟替卡松和噻托溴铵对第1秒用力呼气容积（FEV1）、FEV1/FVC（用力肺活量）和FEV1％（第1秒用力呼气容积占预计值的百分比）的改善作用与单独吸入噻托溴铵比较,差异有统计学意义[加权均数差（95％ CI）分别为0.19（0.13,0.26）、5.21（3.08,7.33）、5.64（3.79,7.48）].联合吸入沙美特罗/氟替卡松和噻托溴铵对FEV1、FEV1/FVC及FEV1％预计值改善作用与单独吸入沙美特罗/氟替卡松相比较,差异有统计学意义[加权均数差（95％ CI）分别为0.18（0.13,0.22）、5.95（3.27,8.64）、7.26（4.56,9.96）].结论 现有研究显示联合吸入沙美特罗/氟替卡松和噻托溴铵对COPD稳定期患者治疗作用优于单独吸入沙美特罗氟替卡松或单独吸入噻托溴铵.