Clinical Benefits of Inhaled Ciclesonide for Hospitalized Patients With COVID-19 Infection

A Retrospective Study

Kuan-Chih Kuo; Chao-Hsien Chen; Chieh-Jen Wang; Jou-Chun Wu; Hsin-Pei Chung; Yen-Ting Chen; Yen-Hsiang Tang; Wen-Kuei Chang; Chang-Yi Lin; Chien-Liang Wu

Disclosures

BMC Pulm Med. 2022;22(368) 

In This Article

Results

In total, 332 patients were diagnosed with COVID-19 during the study period, of whom 63 were excluded (see Figure 1 for details). Finally, 269 patients were enrolled for analysis, of whom 184 received inhaled ciclesonide and 85 did not.

Figure 1.

Flowchart of patient inclusion in the study

The median ages were 62.0 (55.0–71.0) and 62.0 (50.8–74.5) years in the ciclesonide and non-ciclesonide groups, respectively (Table 1). There was no difference in gender distribution. Compared to the non-ciclesonide group, the ciclesonide group had less heart failure (1.1% vs. 12.9%, p < 0.0001) and chronic kidney disease (3.3% vs. 20.0%, p < 0.0001). Regarding baseline disease severity, the ciclesonide group were associated with more severe COVID-19 infection (64.1% vs. 40.0%, p = 0.0002), but were less likely to be categorized as high-risk using Shang's CSS score (34.1% vs. 47.4%, p = 0.0431). The ciclesonide group received more oral/intravenous corticosteroids (90.8% vs. 55.3%, p ≤ 0.0001), remdesivir (44.0% vs. 28.2%, p = 0.0138) and NRICM101 (31.0% vs. 7.1%, p < 0.0001) during hospitalization.

Regarding the primary outcome, the use of inhaled ciclesonide was associated with lower in-hospital mortality (7.6% vs. 23.5%, p = 0.0003) and more frequent use of oxygen supplementation during hospitalization (84.8% vs. 60.0%, p < 0.0001). There was no significant difference in the duration of fever between the two group (2.0 (1.0–3.0) versus 2.0 (1.0–4.0) days, p = 0.1381). In the time-to-mortality analysis, the use of ciclesonide was associated with a significantly lower risk of mortality (hazard ratio: 0.47, 95% confidence interval [CI]: 0.23–0.95, p = 0.0344) (Figure 2).

Figure 2.

Kaplan–Meier curves of the cumulative probability of survival after admission in patients with COVID-19 infection treated with or without inhaled ciclesonide. CI: confidence interval, HR: hazard ratio

The use of inhaled ciclesonide, age, hypertension, diabetes, heart failure, chronic kidney disease, oxygen therapy at admission, high risk Shang's CSS score, treatment with systemic corticosteroids, and tocilizumab were related to in-hospital mortality in univariate analysis (Table 2). These factors were then entered into multivariate analysis, which showed that inhaled ciclesonide was associated with a lower risk of in-hospital mortality (odds ratio: 0.2724, 95% CI: 0.087–0.8763, p = 0.0291) (Table 3).

In subgroup analysis (Table 4), the use of inhaled ciclesonide was associated with a significant reduction in mortality in the patients with severe COVID-19 infection (6.8% vs. 50.0%, p < 0.0001) and those with a high Shang's CSS score (16.4% vs. 43.2%, p = 0.0037). Ciclesonide was also found to reduce the risk of mechanical ventilation use among the patients with severe COVID-19 infection (15.3% vs. 32.4%, p = 0.0259). There were more supplemental oxygen orders during hospitalization for the patients who received ciclesonide with non-severe COVID-19 infection (57.6% vs. 33.3%, p = 0.0095).

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