Maverex Limited, Manchester, UK.
University of Michigan, Women's Respiratory Clinic, Ann Arbor, USA.
Respir Res. 2019 Nov 4;20(1):242. doi: 10.1186/s12931-019-1213-9.
Guidelines recommend that treatment with a long-acting β agonist (LABA), a long-acting muscarinic antagonist (LAMA), and inhaled corticosteroids (ICS), i.e. triple therapy, is reserved for a select group of symptomatic patients with chronic obstructive pulmonary disease (COPD) who continue to exacerbate despite treatment with dual therapy (LABA/LAMA). A number of single-inhaler triple therapies are now available and important clinical questions remain over their role in the patient pathway. We compared the efficacy and safety of single-inhaler triple therapy to assess the magnitude of benefit and to identify patients with the best risk-benefit profile for treatment. We also evaluated and compared study designs and population characteristics to assess the strength of the evidence base.
We conducted a systematic search, from inception to December 2018, of randomised controlled trials (RCTs) of single-inhaler triple therapy in patients with COPD. The primary outcome was the annual rate of moderate and severe exacerbations.
We identified 523 records, of which 15 reports/abstracts from six RCTs were included. Triple therapy resulted in the reduction of the annual rate of moderate or severe exacerbations in the range of 15-52% compared with LAMA/LABA, 15-35% compared to LABA/ICS and 20% compared to LAMA. The patient-based number needed to treat for the moderate or severe exacerbation outcome ranged between approximately 25-50 (preventing one patient from having an event) and the event-based number needed to treat of around 3-11 (preventing one event). The absolute benefit appeared to be greater in patients with higher eosinophil counts or historical frequency of exacerbations and ex-smokers. In the largest study, there was a significantly higher incidence of pneumonia in the triple therapy arm. There were important differences in study designs and populations impacting the interpretation of the results and indicating there would be significant heterogeneity in cross-trial comparisons.
The decision to prescribe triple therapy should consider patient phenotype, magnitude of benefit and increased risk of adverse events. Future research on specific patient phenotype thresholds that can support treatment and funding decisions is now required from well-designed, robust, clinical trials.
PROSPERO #CRD42018102125 .
指南建议，长效β激动剂（LABA）、长效毒蕈碱拮抗剂（LAMA）和吸入皮质类固醇（ICS）三联治疗仅用于经过 LABA/LAMA 双联治疗仍频繁加重的慢性阻塞性肺疾病（COPD）症状性患者。目前有多种单吸入器三联疗法，但其在患者治疗路径中的作用仍存在重要的临床问题。我们比较了单吸入器三联疗法的疗效和安全性，以评估获益程度，并确定治疗获益风险比最佳的患者人群。我们还评估和比较了研究设计和人群特征，以评估证据基础的强度。
我们对截止到 2018 年 12 月的 COPD 患者单吸入器三联治疗的随机对照试验（RCT）进行了系统检索。主要结局是每年中重度加重的发生率。
我们共检索到 523 条记录，其中 6 项 RCT 的 15 篇报告/摘要被纳入。与 LAMA/LABA 相比，三联疗法使中重度加重的年发生率降低 15-52%，与 LABA/ICS 相比降低 15-35%，与 LAMA 相比降低 20%。基于患者的中重度加重事件预防人数（NNT）约为 25-50（预防一个患者发生事件），基于事件的 NNT 约为 3-11（预防一个事件）。在更高嗜酸性粒细胞计数或既往加重频率较高的患者和已戒烟患者中，绝对获益似乎更大。在最大的研究中，三联治疗组肺炎的发生率显著更高。研究设计和人群存在重要差异，影响结果的解释，表明跨试验比较会存在显著的异质性。
处方三联疗法的决定应考虑患者表型、获益程度和不良反应风险增加。目前需要进行设计良好、稳健的临床试验，以确定能够支持治疗和决策的特定患者表型阈值。
PROSPERO #CRD42018102125 。
