GSK, 1250 S Collegeville Rd, Collegeville, PA, 19426, USA.
Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA, 19104, USA.
Adv Ther. 2020 Dec;37(12):4894-4909. doi: 10.1007/s12325-020-01496-7. Epub 2020 Oct 3.
Few studies have utilized 24-h serial spirometry to compare the effects of inhaled chronic obstructive pulmonary disease (COPD) therapies on lung function. The FULFIL study previously reported significant lung function improvements with once-daily single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus twice-daily single-inhaler budesonide/formoterol (BUD/FOR) in patients with symptomatic COPD at risk of exacerbations.
This prespecified analysis evaluated 24-h serial spirometry data from a subgroup of 406 patients in FULFIL. BUD/FOR twice-daily dosing was maintained during 24-h spirometry. A post hoc analysis evaluated serial forced expiratory volume in 1 s (FEV) at day 1 and week 24 by disease severity at screening (FEV < 50% predicted and no moderate or severe exacerbation in prior year, FEV < 50% predicted and ≥ 1 moderate or severe exacerbation in prior year, and FEV ≥ 50% and < 80% predicted and ≥ 2 moderate or ≥ 1 severe exacerbations in prior year).
Odds of achieving a ≥ 100-mL increase from baseline in FEV within the first 6 h post dose on day 1 were significantly greater with FF/UMEC/VI than BUD/FOR [odds ratio 2.79 (95% confidence interval 1.56-4.98); p < 0.001]. FF/UMEC/VI led to greater improvements in weighted mean FEV over 0-6, 0-12, 0-24, and 12-24 h on day 1 and at week 24, with the greatest between-group differences at week 24 (range 196-210 mL; all p < 0.001). Significant between-treatment differences in FEV and forced vital capacity (FVC) in favor of FF/UMEC/VI versus BUD/FOR were seen at all time points at week 24 (FEV range 156-231 mL, all p < 0.001; FVC range 139-309 mL, all p ≤ 0.002). Serial FEV results were consistent irrespective of disease severity at screening.
These findings further demonstrate sustained lung function benefits with once-daily FF/UMEC/VI single-inhaler triple therapy in patients with symptomatic COPD at risk of exacerbations across a range of disease severities.
很少有研究利用 24 小时连续肺功能测定来比较吸入性慢性阻塞性肺疾病（COPD）治疗药物对肺功能的影响。FULFIL 研究先前报道，与每日两次单吸入布地奈德/福莫特罗（BUD/FOR）相比，每日一次单吸入糠酸氟替卡松/乌美溴铵/维兰特罗（FF/UMEC/VI）可显著改善有 COPD 症状且有加重风险患者的肺功能。
本预设定分析从 FULFIL 中 406 例患者的亚组中评估了 24 小时连续肺功能测定数据。在 24 小时肺功能测定期间维持 BUD/FOR 每日两次的剂量。一项事后分析评估了在筛选时按疾病严重程度评估的第 1 天和第 24 周的 24 小时连续用力呼气量 1 秒率（FEV）（FEV<50%预测值且前一年无中度或重度加重，FEV<50%预测值且前一年有≥1 次中度或重度加重，FEV≥50%且<80%预测值且前一年有≥2 次中度或≥1 次重度加重）。
与 BUD/FOR 相比，在第 1 天第 1 个 6 小时内，从基线开始，FEV 增加≥100 毫升的可能性，使用 FF/UMEC/VI 治疗的可能性明显更高[比值比 2.79（95%置信区间 1.56-4.98）；p<0.001]。FF/UMEC/VI 在第 1 天和第 24 周时，在 0-6、0-12、0-24 和 12-24 小时时，FEV 的加权平均改善程度更大，在第 24 周时组间差异最大（范围 196-210 毫升；均 p<0.001）。在第 24 周的所有时间点，与 BUD/FOR 相比，FEV 和用力肺活量（FVC）均有明显的治疗效果差异，有利于 FF/UMEC/VI（FEV 范围 156-231 毫升，均 p<0.001；FVC 范围 139-309 毫升，均 p≤0.002）。无论筛选时疾病的严重程度如何，FEV 的连续测定结果均一致。
这些发现进一步证明，在有 COPD 症状且有加重风险的患者中，每日一次 FF/UMEC/VI 三联吸入疗法可持续改善肺功能，且适用于各种严重程度的疾病。
