茚达特罗对COPD患者安全有效

亚特兰大——美国胸内科医师协会(ACCP)年会上公布的两项汇总分析(疗效分析和安全性分析)显示，茚达特罗可显著改善慢性阻塞性肺病(COPD)患者的支气管扩张和健康状况，并且安全性和耐受性较好。

Thomas Siler博士

疗效分析从两项设计相同的研究纳入640例随机接受茚达特罗或安慰剂治疗12周的患者。患者的平均年龄为63岁，沙丁胺醇给药后的平均FEV₁为预期值的54%。约40%的患者正在使用吸入式糖皮质激素。

结果显示，给药后24 h的1秒用力呼气量(FEV₁)谷值在男性和女性中分别改善150和110 Ml(最小二乘均差，下同)，在65岁以下患者和65岁以上患者中分别改善110和150 ml，在中度和重度气流受限的患者中分别改善150和110 ml，在既往吸烟者和当前吸烟者中分别改善140和130 ml。

采用圣乔治呼吸问卷测定的健康状况评分在男性和女性中的改善相似(分别改善3.8和3.7单位)，在所有其他组中的改善也相似。然而，65岁以上患者的改善大于65岁以下患者(4.5单位 vs. 3.3单位)，重度气流受限患者的改善大于中度气流受限患者(4.6单位 vs. 3.3单位)，既往吸烟者的改善大于当前吸烟者(4.1单位 vs. 3.5单位)。茚达特罗组和安慰剂组的不良事件发生率分别为44%~57%和40%~48%。在两组中，65岁以上患者、女性、中度气流受限患者和既往吸烟患者的不良事件较高。

疗效分析结果表明，茚达特罗可成功用于治疗COPD患者，预期支气管扩张和健康状况方面均可获得明显改善。

安全性分析纳入来自既往多项研究和美国及加拿大患者数据库中的约2500例患者，其中449例患者接受茚达特罗治疗3个月，2012例对照患者接受安慰剂治疗。结果显示，茚达特罗组和安慰剂组的脑和心血管不良事件(CCV AE)总体发生率相似，分别为2.0%和2.58%。茚达特罗组任何一种CCVAE的发生例数均不超过2例。茚达特罗组和安慰剂组的严重CCV AE例数分别为2例和13例，抗血小板试验者协作组(APTC)事件(即被认为与研究治疗无关的脑血管意外)例数分别为1例和8例。在一个6个月研究人群中，CCV AE总体发生率为3.3%~5.8%，在每日剂量75~600 mcg范围内，未观察到剂量与CCV AE之间呈量效关系。在接受茚达特罗75 mcg治疗的患者中未观察到死亡。

安全性分析结果表明，使用剂量为75 mcg的茚达特罗治疗中至重度COPD患者，CCV安全性可以接受。

上述疗效分析和安全性分析结果应可使临床医生放心使用该药治疗COPD患者。

安全性分析纳入的研究由茚达特罗生产商诺华公司资助。分析人员声明与诺华和其他药企存在联系。

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By: SHARON WORCESTER, Cardiology News Digital Network

ATLANTA – Indacaterol significantly improves bronchodilation and health status in patients with chronic obstructive pulmonary disease, and is safe and well tolerated, according to findings from studies presented at the annual meeting of the American College of Chest Physicians.

In a pooled analysis of efficacy and safety data from two randomized controlled studies, the inhaled long-acting beta2-agonist bronchodilator given at the approved dose of 75 mcg daily was found to be of benefit regardless of age, sex, smoking status, or severity of airflow limitation. In another analysis of pooled data, treatment was shown to have an acceptable cardiovascular and cerebrovascular safety profile.

The efficacy analysis included 640 patients from two identically designed studies who were randomized to receive indacaterol or placebo for 12 weeks. Trough (24 hours post dose) forced expiratory volume in 1 second (FEV1) improved by least-squares mean differences of 150 and 110 mL among men and women, respectively; by 110 and 150 mL among those under age 65 and those aged 65 or older; by 150 and 110 mL among those with moderate and severe airflow limitation; and by 140 and 130 mL in ex-smokers and current smokers, Dr. Thomas Siler of Midwest Chest Consultants in St. Charles, Mo., reported.

Health status scores, as measured using the St. George’s Respiratory Questionnaire, improved similarly in men and women (by 3.8 and 3.7 units, respectively), and also improved in all of the other groups. Improvement was greater, however, in those aged 65 years and older (by 4.5 units vs. 3.3 units in those under age 65), those with severe airflow limitation (by 4.6 units vs. 3.3 units in those with moderate airflow limitation), and in ex-smokers (by 4.1 vs. 3.5 units in current smokers).

Adverse events occurred in 44%-57% of patients receiving indacaterol and in 40%-48% of patients receiving placebo. More adverse events in both groups occurred in older patients, women, those with moderate disease, and ex-smokers.

Patients in this study had a mean age of 63 years, and a mean post-albuterol FEV1 of 54% predicted. About 40% were receiving inhaled corticosteroids.

The findings suggest that indacaterol can be successfully used to treat a range of COPD patients, Dr. Siler concluded. Treatment can be expected to lead to "substantial and worthwhile improvements in bronchodilation and health status," he added.

According to findings from a separate analysis of pooled data from nearly 2,500 patients, these improvements come without an increase in the risk of cerebro- and cardiovascular adverse events (CCV AEs).

The overall frequency of CCV AEs was similar in 449 patients treated for up to 3 months and 2,012 control patients who received placebo (2.0% and 2.58%, respectively), and no type of CCV AE occurred in more than 2 patients in the active treatment group, Dr. James Donohue reported.

Serious CCV AEs occurred in 2 patients in the treatment group and 13 in the placebo group, and an Antiplatelet Trialists’ Collaboration (APTC) event (a cerebrovascular accident not believed to be related to study treatment) occurred in 1 patient in the treatment group, compared with 8 patients in the control group, said Dr. Donohue of the University of North Carolina, Chapel Hill.

The overall frequency of patients with CCV AEs in a 6-month study population ranged from 3.3% to 5.8%, and no dose-response relationship was seen between the 75-mcg dose and up to 600 mcg daily for CCV AEs.

No deaths were reported in those receiving indacaterol 75.

These findings, which used pooled data from previous studies and a database of U.S. and Canadian patients, indicate that indacaterol given at the 75-mcg dose has an acceptable CCV safety profile in patients with moderate to severe COPD, Dr. Donohue said.

When considered in the context of the efficacy data, the findings should be very reassuring to clinicians, he concluded.

The studies included in the safety analysis were sponsored by Novartis. Dr. Donohue and Dr. Siler reported financial relationships with Novartis, which makes indacaterol, as well as with other industry companies. Dr. Donohue reported receiving fees for consulting and/or serving on speakers bureaus or advisory committees for Novartis, GSK, Boehringer-Ingelheim, and other companies. Dr. Siler reported receiving grant monies from GSK, Novartis, Boehringer-Ingelheim, and other companies. He also reported receiving fees for consulting, serving on speakers bureaus, and/or serving on advisory committees for Boehringer-Ingelheim, AstraZeneca, and Forest Research Institute.