Disproportionate increase in COPD exacerbation risk for 3 months after discontinuing LAMA or ICS: insights from the FLAME trial.

Discontinuing inhaled corticosteroids (ICS) can trigger withdrawal effects transiently increasing exacerbation risk; but evidence for long-acting muscarinic antagonists (LAMA) withdrawal remains limited.

停止使用吸入性皮质类固醇（ICS）可能会暂时触发戒断反应，增加急性加重的风险；但关于长效毒蕈碱拮抗剂（LAMA）停药的证据仍然有限。

Methods

We performed a post hoc analysis of the 52-week, double-blind, Effect of Indacaterol Glycopyrronium versus Fluticasone Salmeterol on COPD Exacerbations trial that compared long-acting beta-2 agonist (LABA)+LAMA with LABA+ICS in 3362 patients with moderate-to-severe COPD and exacerbation history.

我们对一项为期52周的双盲研究进行了事后分析，该研究比较了长效β2受体激动剂（LABA）+长效抗胆碱药（LAMA）与LABA+吸入性糖皮质激素（ICS）对3362名中重度COPD患者和有加重病史的患者的影响。

Potential withdrawal effects after discontinuing LAMA or ICS were suggested by monthly exacerbation incidenceplots during the first quarter of follow-up.

在随访的前一季度，每月加重发生率的图表暗示了在停用LAMA或ICS后可能出现的潜在撤药效应。

Participants were stratified by their baseline use of these therapies, and outcomes were compared between the first and subsequent quarters among those who continued versus discontinued each treatment.

参与者根据基线时使用这些疗法的情况进行了分层，比较了继续使用与停止每种治疗的患者在第一季度和随后季度之间的结果。

Multivariable mixed-effects models assessed differences in exacerbation rates, with temporal variation in treatment effects interpreted as indicative of withdrawal effects.

多变量混合效应模型评估了急性加重率的差异，治疗效果的时间变化被解释为撤药效应的指标。

Results

Discontinuing LAMA was associated with a marked, transient increase in moderate-to-severe exacerbations during the first versus subsequent quarters (p=0.001; rate ratio up to 2.2 (95% CI 1.2 to 4.1) in the subgroup least influenced by concomitant ICS use).

停用长效抗胆碱药物（LAMA）与在第一个季度与随后季度相比，中度至重度急性加重的显著且短暂增加有关（p=0.001；在受同时使用吸入性糖皮质激素（ICS）影响最小的亚组中，发生率比达到2.2（95%置信区间1.2至4.1））。

This observation was not confirmed for severe exacerbations, likely due to low event count.

这一观察结果对于重度急性加重并未得到证实，可能是由于事件数量较少。

In contrast, discontinuing ICS was associated with a significant early rise in severe exacerbations (p=0.023), though the difference for moderate-to-severe events did not reach statistical significance.

相比之下，停用ICS与严重加重事件的显著早期增加相关（p=0.023），尽管中度至重度事件的差异未达到统计学意义。

Importantly, ICS withdrawal effects appeared consistent regardless of baseline blood eosinophil count.

重要的是，ICS撤除效应似乎与基线血嗜酸性粒细胞计数无关，表现出一致性。

Conclusions

Our findings suggest potent LAMA and ICS treatment withdrawal effects on exacerbations, highlighting the importance of treatment adherence and accounting for withdrawal effects in clinical trials.

我们的研究结果表明，停用长效抗胆碱药物(LAMA)和吸入性皮质类固醇(ICS)对急性加重事件有显著的抑制作用，这突显了治疗依从性的重要性，并提示在临床试验中需要考虑停药效应。

trial_registration_number

NCT01782326.

NCT01782326。