The University of Manchester, Medicines Evaluation Unit, Centre for Respiratory and Allergy Medicine, University Hospital of South Manchester Foundation Trust, Manchester, M23 9QZ, UK.
Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, Canada.
Respir Res. 2017 May 30;18(1):106. doi: 10.1186/s12931-017-0583-0.
'Clinically important deterioration' (CID) is a composite endpoint measuring worsening of the key clinical features of chronic obstructive pulmonary disease (COPD), namely lung function, patient-reported outcomes, and exacerbations. ACLIFORM and AUGMENT were two 24-week, randomized, double-blind, phase III studies assessing twice-daily (BID) aclidinium bromide (AB) 400 μg/formoterol fumarate (FF) 12 μg. This pooled post-hoc analysis assessed the effects of AB/FF 400/12 μg on both first and sustained CID events versus placebo and monotherapies in patients with moderate to severe COPD.
A first CID event was defined as the occurrence of a moderate/severe exacerbation or the worsening from baseline in ≥1 of the following: trough forced expiratory volume in 1 second (FEV; ≥100 mL), Transition Dyspnea Index (TDI) focal score (≥1 unit), or St George's Respiratory Questionnaire (SGRQ) total score (≥4 units). A 'sustained' CID was defined as a worsening maintained at all subsequent visits from appearance to week 24 or a moderate/severe exacerbation at any time. CID events were assessed at three visits (weeks 4, 12, and 24); trough FEV was also measured at weeks 1 and 18.
AB/FF 400/12 μg reduced the risk of a first CID event by 45% versus placebo (hazard ratio [HR] 0.55, p < 0.001), 18% versus FF 12 μg (HR 0.82, p < 0.01), and 15% versus AB 400 μg (HR 0.85, p < 0.05). Similarly, AB/FF 400/12 μg reduced the risk of a sustained CID event by 48% versus placebo (HR 0.52, p < 0.001) and 22% versus FF 12 μg (HR 0.78, p < 0.01). AB/FF 400/12 μg reduced the risk of a first or sustained CID event for all four components versus placebo (trough FEV and TDI, first and sustained CID, all p < 0.001; SGRQ first CID p < 0.001; SGRQ sustained CID, p < 0.01; exacerbations first and sustained CID, both p < 0.05) and TDI and SGRQ versus FF 12 μg (TDI, first and sustained CID both p < 0.05; SGRQ first CID p < 0.01), and SGRQ versus AB 400 μg (first CID, p < 0.05).
AB/FF 400/12 μg BID may provide greater airway stability and fewer exacerbations or deteriorations in lung function, health status, or dyspnea compared with placebo or monotherapies.
Clinicaltrials.gov NCT01462942 (ACLIFORM); registered 26 October 2011. Clinicaltrials.gov NCT01437397 (AUGMENT); registered 19 September 2011.
“临床重要恶化（CID）”是一个复合终点，用于衡量慢性阻塞性肺疾病（COPD）关键临床特征的恶化，即肺功能、患者报告的结局和加重。ACLIFORM 和 AUGMENT 是两项为期 24 周、随机、双盲、III 期研究，评估了每日两次（BID）给予阿地溴铵（AB）400μg/富马酸福莫特罗（FF）12μg。这项汇总的事后分析评估了 AB/FF 400/12μg 与安慰剂和单药治疗相比，在中重度 COPD 患者中对首次和持续 CID 事件的影响。
首次 CID 事件定义为发生中度/重度加重或以下至少 1 项自基线恶化：用力呼气量（FEV）的第 1 秒时间（FEV1）峰值（≥100mL）、转移呼吸困难指数（TDI）焦点评分（≥1 单位）或圣乔治呼吸问卷（SGRQ）总评分（≥4 单位）。“持续”CID 定义为在首次出现至第 24 周的所有后续就诊中持续恶化，或在任何时候发生中度/重度加重。CID 事件在三个访视点评估（第 4、12 和 24 周）；FEV1 也在第 1 和第 18 周测量。
AB/FF 400/12μg 与安慰剂相比，首次 CID 事件的风险降低了 45%（风险比[HR]0.55，p<0.001），与 FF 12μg 相比降低了 18%（HR 0.82，p<0.01），与 AB 400μg 相比降低了 15%（HR 0.85，p<0.05）。同样，AB/FF 400/12μg 与安慰剂相比，持续 CID 事件的风险降低了 48%（HR 0.52，p<0.001），与 FF 12μg 相比降低了 22%（HR 0.78，p<0.01）。AB/FF 400/12μg 与安慰剂相比，所有四个组成部分的首次或持续 CID 事件风险均降低（FEV1 峰值和 TDI，首次和持续 CID，均 p<0.001；SGRQ 首次 CID p<0.001；SGRQ 持续 CID，p<0.01；首次和持续 CID 加重，均 p<0.05）和 TDI 和 SGRQ 与 FF 12μg 相比（TDI，首次和持续 CID 均 p<0.05；SGRQ 首次 CID p<0.01），与 AB 400μg 相比 SGRQ（首次 CID，p<0.05）。
与安慰剂或单药治疗相比，AB/FF 400/12μg 每日两次给药可能提供更大的气道稳定性，并减少加重或肺功能、健康状况或呼吸困难恶化。
Clinicaltrials.gov NCT01462942（ACLIFORM）；于 2011 年 10 月 26 日注册。Clinicaltrials.gov NCT01437397（AUGMENT）；于 2011 年 9 月 19 日注册。
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