The George Institute for Global Health, Sydney, Australia
Faculty of Medicine, UNSW Sydney, Sydney, Australia.
Eur Respir J. 2021 Jun 10;57(6). doi: 10.1183/13993003.03338-2020. Print 2021 Jun.
The highest burden of chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries. Low-cost oral medications, if effective, could enable affordable, accessible COPD treatment.
In this randomised, three-arm, double-blind, double-dummy, placebo-controlled study conducted in 37 centres in China, symptomatic patients with moderate to very severe COPD were randomised 1:1:1 to placebo twice daily plus placebo once daily, low-dose theophylline 100 mg twice daily plus placebo once daily or low-dose theophylline 100 mg twice daily plus low-dose oral prednisone 5 mg once daily for 48 weeks. The primary end-point was annualised exacerbation rate.
1670 subjects were randomised and 1242 completed the study (1142 with acceptable data at week 48). Subjects (75.7% male) had a mean age of 64.4 years, with mean±sd baseline post-bronchodilator forced expiratory volume in 1 s (FEV) 1.1±0.4 L (42.2% predicted) and St George's Respiratory Questionnaire (SGRQ) score 45.8±20.1. There were negligible differences between annualised exacerbation rates across the three treatments: 0.89 (95% CI 0.78-1.02) on theophylline plus prednisone, 0.86 (95% CI 0.75-0.99) on theophylline plus placebo and 1.00 (95% CI 0.87-1.14) on placebo. The rate ratio for theophylline plus prednisone pooled theophylline plus placebo and placebo was 0.96 (95% CI 0.83-1.12), for theophylline plus placebo placebo was 0.87 (95% CI 0.73-1.03; p=0.101) and for theophylline plus prednisone placebo was 0.90 (95% CI 0.76-1.06; p=0.201). Secondary outcomes of hospitalisations, FEV, SGRQ and COPD Assessment Test score showed no statistically significant difference between treatment arms. Serious adverse events other than exacerbations were <2% and did not differ between treatment arms.
Low-dose theophylline alone or in combination with prednisone did not reduce exacerbation rates or clinically important secondary end-points compared with placebo.
慢性阻塞性肺疾病（COPD）的负担最高发生在中低收入国家。如果低成本的口服药物有效，那么将能够负担得起和可获得的 COPD 治疗。
在这项在中国 37 个中心进行的随机、三臂、双盲、双模拟、安慰剂对照研究中，有症状的中重度 COPD 患者按 1:1:1 的比例随机分为两组，一组每天两次给予安慰剂和一次安慰剂，另一组每天两次给予低剂量茶碱 100mg 和一次安慰剂，或每天两次给予低剂量茶碱 100mg 和一次低剂量口服泼尼松 5mg，疗程为 48 周。主要终点是年恶化率。
1670 名受试者被随机分组，1242 名受试者完成了研究（48 周时有 1142 名受试者的数据可接受）。受试者（75.7%为男性）的平均年龄为 64.4 岁，平均基线支气管扩张剂后 1 秒用力呼气量（FEV）为 1.1±0.4L（预测值的 42.2%），圣乔治呼吸问卷（SGRQ）评分为 45.8±20.1。三种治疗方法的年恶化率差异很小：茶碱加泼尼松组为 0.89（95%可信区间 0.78-1.02），茶碱加安慰剂组为 0.86（95%可信区间 0.75-0.99），安慰剂组为 1.00（95%可信区间 0.87-1.14）。茶碱加泼尼松与茶碱加安慰剂联合安慰剂的率比为 0.96（95%可信区间 0.83-1.12），茶碱加安慰剂与安慰剂的率比为 0.87（95%可信区间 0.73-1.03；p=0.101），茶碱加泼尼松与安慰剂的率比为 0.90（95%可信区间 0.76-1.06；p=0.201）。次要结局包括住院、FEV、SGRQ 和 COPD 评估测试评分，治疗组之间没有统计学意义上的差异。除恶化外的其他严重不良事件发生率<2%，且治疗组之间无差异。
与安慰剂相比，单独使用低剂量茶碱或与泼尼松联合使用并不能降低恶化率或临床上重要的次要终点。
