Predicting benefit from adjuvant therapy with corticosteroids in community-acquired pneumonia: a data-driven analysis of randomised trials.

Methods

In this individual patient data meta-analysis, we included RCTs published before July 1, 2024, comparing adjuvant treatment with corticosteroids versus placebo in patients hospitalised with CAP.

在这项个体患者数据的荟萃分析中，我们纳入了截至2024年7月1日发表的比较皮质类固醇辅助治疗与安慰剂的RCTs，这些试验针对的是因CAP住院的患者。

The primary endpoint was 30-day all-cause mortality, collected across all trials, and analyses followed the intention-to-treatprinciple.

主要终点是所有试验中收集的30天全因死亡率，并且分析遵循了意向治疗原则。

We analysed HTE using risk and effect modelling.

我们使用风险和效应建模分析了治疗效果的异质性。

For risk modelling, patients were classified as having less severe or severe CAP based on the pneumonia severity index (PSI), comparing PSI class I-III versus class IV-V.

在风险建模中，根据肺炎严重指数（PSI），将患者分类为轻度或重度社区获得性肺炎（CAP），比较PSI I-III级与IV-V级。

For effect modelling, we trained a corticosteroid-effect model on six trials and externally validated it using data from two trials, received after model preregistration.

在效果建模中，我们在六个试验上训练了一个皮质类固醇效果模型，并在模型预注册后，使用两个试验的数据进行了外部验证。

This model classified patients into two groups: no predicted benefit and predicted benefit from adjuvant treatment with corticosteroids.

该模型将患者分为两组：一组无预测的辅助治疗皮质类固醇的益处，另一组有预测的益处。

The literature search was registered on PROSPERO, CRD42022380746.

文献检索已在PROSPERO上注册，CRD42022380746。

Results

We included eight RCTs with 3224 patients.

我们纳入了八项随机对照试验，共3224名患者。

Across all eight trials, 246 (7·6%) patients died within 30 days (106 [6·6%] of 1618 in the corticosteroid group vs 140 [8·7%] of 1606 in the placebo group; odds ratio [OR] 0·72 [95% CI 0·56-0·94], p=0·017).

在所有八项试验中，有246名（7.6%）患者在30天内死亡（皮质类固醇组1618名患者中有106名（6.6%），安慰剂组1606名患者中有140名（8.7%）；优势比[OR]为0.72（95%置信区间0.56-0.94），p=0.017）。

The corticosteroid-effect model, which selected C-reactive protein (CRP), showed significant HTE during external validation in the two most recent trials.

选择C反应蛋白(CRP)的皮质类固醇效应模型，在最近两项试验的外部验证中显示出显著的异质性治疗效果( HTE )。

In these trials, 154 (11·4%) of 1355 patients died within 30 days (88 [13·1%] of 671 in the placebo group vs 66 [9·6%] of 684 in the corticosteroid group; OR 0·71 [95% CI 0·50-0·99], p=0·044).

在这些试验中，1355名患者中有154名（11.4%）在30天内死亡（安慰剂组671名患者中有88名（13.1%），皮质类固醇组684名患者中有66名（9.6%）；OR 0.71 [95% 置信区间 0.50-0.99]，p=0.044）。

Among patients predicted to have no benefit (CRP ≤204 mg/L, n=725), no significant effect was observed (OR 0·98 [95% CI 0·63-1·50]), whereas for those with predicted benefit (CRP >204 mg/L, n=630), 39 (13·0%) of 301 patients died in the placebo group compared with 20 (6·1%) of 329 in the corticosteroid group (0·43 [0·25-0·76], pinteraction=0·026).

在预测无获益的患者中（CRP ≤204 mg/L, n=725），未观察到显著效果（OR 0·98 [95% 置信区间 0·63-1·50]），而对于预测有获益的患者（CRP >204 mg/L, n=630），在安慰剂组中有39 (13·0%) 名患者死亡，而在皮质类固醇组中有20 (6·1%) 名患者死亡（0·43 [0·25-0·76]，pinteraction=0·026）。

No significant HTE was found between less severe CAP (PSI class I-III, n=229) and severe CAP (PSI class IV-V, n=1126).

在轻度社区获得性肺炎（PSI I-III级，n=229）和重度社区获得性肺炎（PSI IV-V级，n=1126）之间未发现显著的异质性治疗效果（HTE）。

Corticosteroid therapy significantly increased hyperglycaemia risk (44 [12·8%] of 344 in the placebo group vs 84 [24·8%] of 339 in the corticosteroid group; OR 2·50 [95% CI 1·63-3·83], p<0·0001) and hospital re-admission risk (30 [3·7%] of 814 in the placebo group vs 57 [7·0%] of 819 in the corticosteroid group; 1·95 [1·24-3·07], p=0·0038).

皮质类固醇治疗显著增加了高血糖的风险（安慰剂组344人中有44人[12.8%]，皮质类固醇组339人中有84人[24.8%]；比值比2.50 [95% 置信区间1.63-3.83]，p<0.0001）和再次入院的风险（安慰剂组814人中有30人[3.7%]，皮质类固醇组819人中有57人[7.0%]；比值比1.95 [1.24-3.07]，p=0.0038）。

interpretation

Overall, adjuvant therapy with corticosteroids significantly reduces 30-day mortality in patients hospitalised with CAP.

总体而言，皮质类固醇作为辅助治疗显著降低了因社区获得性肺炎（CAP）住院患者的30天死亡率。

The treatment effect varied significantly among subgroups based on CRP concentrations, with a substantial mortality reduction observed only in patients with high baseline CRP.

治疗效果在基于C反应蛋白（CRP）浓度的亚组中存在显著差异，仅在基线CRP水平高的患者中观察到显著的死亡率降低。

funding

None.

无。