GSK, Via Fiorentina 1, Siena 53100, Italy.
Allegheny Health Network, Erie, PA, USA.
Vaccine. 2022 Sep 29;40(41):5924-5932. doi: 10.1016/j.vaccine.2022.08.053. Epub 2022 Sep 6.
An investigational vaccine containing non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis (Mcat) surface proteins did not show vaccine efficacy (VE) against combined moderate and severe (moderate/severe) exacerbations in a randomised, observer-blinded, placebo-controlled phase 2b trial of patients with chronic obstructive pulmonary disease (COPD). Nevertheless, observations on rates of severe exacerbations and hospitalisations encouraged further evaluation.
Patients with stable COPD (moderate to very severe airflow limitation, Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 2-4), 40-80 years and at least one moderate/severe exacerbation in the last year received two doses of NTHi-Mcat vaccine or placebo plus standard care. Secondary analyses were conducted on VE against exacerbations according to severity. Potential predictive factors at baseline for VE against severe exacerbations were explored in post-hoc analyses.
Of 606 patients enrolled, 571 were included in the efficacy analysis (279 in NTHi-Mcat vaccine group, 292 in placebo group). VE against severe acute exacerbations of COPD (AECOPD) in various subgroups was 52.11 % (p = 0.015; frequent exacerbators), 65.43 % (p = 0.015; baseline GOLD grade 4), 38.24 % (p = 0.034; previous pneumococcal and/or influenza vaccination). VE was 52.49 % (p = 0.044) for the 6-12 months period after 1 month post-dose 2. Multivariable analysis identified two factors (frequent exacerbator status plus inhaled corticosteroid use at baseline) associated with significant VE against severe AECOPD; in this subpopulation, VE was 74.99 % (p < 0.001).
Results suggest potential efficacy with the NTHi-Mcat vaccine against severe exacerbations in certain patients with COPD, in particular those who have frequent exacerbations and use inhaled corticosteroids. This potential signal requires confirmation in an appropriately designed prospective clinical trial.
ClinicalTrials.gov, NCT03281876.
在一项针对慢性阻塞性肺疾病（COPD）患者的随机、观察者盲、安慰剂对照的 2b 期试验中，含有非分型流感嗜血杆菌（NTHi）和卡他莫拉菌（Mcat）表面蛋白的研究性疫苗并未显示出对联合中重度（中重度）加重的疫苗疗效（VE）。然而，对重度加重和住院率的观察结果鼓励进一步评估。
稳定期 COPD 患者（中至重度气流受限，全球慢性阻塞性肺疾病倡议[GOLD] 2-4 期），年龄 40-80 岁，过去一年至少有一次中重度/重度加重，接受两次 NTHi-Mcat 疫苗或安慰剂加标准治疗。对根据严重程度进行的 VE 进行了次要分析。在事后分析中探索了基线时对重度加重 VE 的潜在预测因素。
606 名入组患者中，571 名纳入疗效分析（NTHi-Mcat 疫苗组 279 名，安慰剂组 292 名）。各种亚组中对重度 COPD 急性加重（AECOPD）的 VE 为 52.11%（p=0.015；频繁加重者），65.43%（p=0.015；基线 GOLD 4 级），38.24%（p=0.034；既往肺炎球菌和/或流感疫苗接种）。在第 2 剂后 1 个月至第 6-12 个月期间，VE 为 52.49%（p=0.044）。多变量分析确定了两个与重度 AECOPD 显著 VE 相关的因素（基线时频繁加重者状态和吸入皮质类固醇的使用）；在该亚组中，VE 为 74.99%（p<0.001）。
结果表明，NTHi-Mcat 疫苗对某些 COPD 患者的重度加重有潜在疗效，尤其是那些频繁加重且使用吸入皮质类固醇的患者。这一潜在信号需要在适当设计的前瞻性临床试验中加以证实。
ClinicalTrials.gov，NCT03281876。
