德国大汉斯多夫肺病医院Klaus F. Rabe团队评估了两种糖皮质激素剂量的三联吸入疗法治疗中重度COPD的疗效和安全性。相关论文于2020年6月24日发表在《新英格兰医学杂志》上。

吸入糖皮质激素、长效毒蕈碱拮抗剂（LAMA）和长效β2-激动剂（LABA）的三联疗法可有效治疗慢性阻塞性肺疾病（COPD），目前已对吸入糖皮质激素的单剂量水平进行了评估，但尚缺乏对其他两种药物剂量水平的研究。

在一项为期52周、临床3期、随机对照试验中，研究组招募了8509例中重度COPD患者，他们在过去一年中至少发生一次病情恶化，按1：1：1：1的比例随机分配，其中2137例患者接受吸入320μg布地奈德+18μg格隆溴铵+9.6 μg福莫特罗的三联疗法；2121例接受吸入160μg布地奈德+18μg格隆溴铵+9.6 μg福莫特罗的三联疗法；2120例患者接受18μg格隆溴铵+9.6 μg福莫特罗的二联疗法；2131例患者接受320μg布地奈德+9.6 μg福莫特罗的二联疗法，均每日两次。

320μg布地奈德三联疗法组中每人每年COPD恶化1.08次，160μg布地奈德三联疗法组为1.07次，格隆溴铵-福莫特罗组为1.42次，布地奈德-福莫特罗组为1.24次。320μg布地奈德三联疗法组和160μg布地奈德三联疗法组的恶化率均显著低于格隆溴铵-福莫特罗组或布地奈德-福莫特罗组。各治疗组中全因不良事件的发生率相差不大。在包含吸入糖皮质激素的组中，确诊肺炎的发生率为3.5％-4.5％，但在格隆溴铵-福莫特罗组中则为2.3％。

总之，布地奈德（160μg或320μg剂量）+格隆溴铵+福莫特罗每天两次的三联疗法，与格隆溴铵+福莫特罗或布地奈德+福莫特罗相比，可显著降低中重度COPD的恶化率。

附：英文原文

Title: Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD | NEJM

Author: Klaus F. Rabe, M.D., Ph.D.,, Fernando J. Martinez, M.D.,, Gary T. Ferguson, M.D.,, Chen Wang, M.D., Ph.D.,, Dave Singh, M.D.,, Jadwiga A. Wedzicha, M.D.,, Roopa Trivedi, M.S.,, Earl St. Rose, M.S.,, Shaila Ballal, M.S.,, Julie McLaren, M.D.,, Patrick Darken, Ph.D.,, Magnus Aurivillius, M.D., Ph.D.,, Colin Reisner, M.D.,, and Paul Dorinsky, M.D.

Issue&Volume: 2020-06-24

Abstract: Abstract

Background

Triple fixed-dose regimens of an inhaled glucocorticoid, a long-acting muscarinic antagonist (LAMA), and a long-acting β2-agonist (LABA) for chronic obstructive pulmonary disease (COPD) have been studied at single dose levels of inhaled glucocorticoid, but studies at two dose levels are lacking.

Methods

In a 52-week, phase 3, randomized trial to evaluate the efficacy and safety of triple therapy at two dose levels of inhaled glucocorticoid in patients with moderate-to-very-severe COPD and at least one exacerbation in the past year, we assigned patients in a 1:1:1:1 ratio to receive twice-daily inhaled doses of triple therapy (inhaled glucocorticoid [320 μg or 160 μg of budesonide], a LAMA [18 μg of glycopyrrolate], and a LABA [9.6 μg of formoterol]) or one of two dual therapies (18 μg of glycopyrrolate plus 9.6 μg of formoterol or 320 μg of budesonide plus 9.6 μg of formoterol). The primary end point was the annual rate (the estimated mean number per patient per year) of moderate or severe COPD exacerbations, as analyzed in the modified intention-to-treat population with the use of on-treatment data only.

Results

The modified intention-to-treat population comprised 8509 patients. The annual rates of moderate or severe exacerbations were 1.08 in the 320-μg–budesonide triple-therapy group (2137 patients), 1.07 in the 160-μg–budesonide triple-therapy group (2121 patients), 1.42 in the glycopyrrolate–formoterol group (2120 patients), and 1.24 in the budesonide–formoterol group (2131 patients). The rate was significantly lower with 320-μg–budesonide triple therapy than with glycopyrrolate–formoterol (24% lower: rate ratio, 0.76; 95% confidence interval [CI], 0.69 to 0.83; P<0.001) or budesonide–formoterol (13% lower: rate ratio, 0.87; 95% CI, 0.79 to 0.95; P=0.003). Similarly, the rate was significantly lower with 160-μg–budesonide triple therapy than with glycopyrrolate–formoterol (25% lower: rate ratio, 0.75; 95% CI, 0.69 to 0.83; P<0.001) or budesonide–formoterol (14% lower: rate ratio, 0.86; 95% CI, 0.79 to 0.95; P=0.002). The incidence of any adverse event was similar across the treatment groups (range, 61.7 to 64.5%); the incidence of confirmed pneumonia ranged from 3.5 to 4.5% in the groups that included inhaled glucocorticoid use and was 2.3% in the glycopyrrolate–formoterol group.

Conclusions

Triple therapy with twice-daily budesonide (at either the 160-μg or 320-μg dose), glycopyrrolate, and formoterol resulted in a lower rate of moderate or severe COPD exacerbations than glycopyrrolate–formoterol or budesonide–formoterol.

DOI: 10.1056/NEJMoa1916046

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1916046