Short- and long-term comparative effectiveness of nirmatrelvir/ritonavir and molnupiravir in asthma patients: a cohort study

Abstract

Background: Few studies evaluated the effectiveness of COVID-19 antivirals specifically in the asthma population This study assessed short- and long-term effects of nirmatrelvir/ritonavir versus molnupiravir in asthma population.

Methods: This is a retrospective cohort study on adult asthma patients infected with COVID-19, using real-world data obtained from the health officials in Hong Kong. Key inclusion criteria were infection with COVID-19 between March 16, 2022, and Oct 30, 2023, age ≥ 18 years, previous asthma diagnosis, and prescription history of an asthma medication. Outcomes included acute and post-acute mortality, post-acute all-cause hospitalization, and cause-specific hospitalization.

Results: 1,745 patients were eligible for this study, with a median follow-up time of 365 days (IQR: 335-365). Patients in the nirmatrelvir/ritonavir group had significantly lower risks of acute inpatient death (HR, 0·27 [95% CI, 0·12 to 0·59]; p = 0·0011), post-acute inpatient death (HR, 0·49 [95% CI, 0·28 to 0·85]; p = 0·011), all-cause hospitalization (HR, 0·72 [95% CI, 0·58 to 0·89]; p = 0·0020), and myocardial infarction (HR, 0·10 [95% CI, 0·01 to 0·92]; p = 0·042) than patients in the control group. The risk of all-cause hospitalization was significantly lower in the nirmatrelvir/ritonavir group compared to the molnupiravir group (HR, 0·65 [95% CI, 0·52 to 0·81]; p = 0·00012). Among patients who were prescribed medium-/ high-dose inhaled corticosteroids, the nirmatrelvir/ritonavir group had a lower hazard of asthma exacerbation than the molnupiravir group (HR, 0·58 [95% CI, 0·35 to 0·95]; p = 0.030).

Conclusion: Compared with molnupiravir, nirmatrelvir/ritonavir may offer more benefits in reducing the risk of post-acute sequelae of COVID-19 among asthma patients. In addition, the post-acute benefits of the antivirals were also demonstrated in patients with mild asthma, which have not been generally recommended in existing clinical management guidelines.

Keywords: Asthma; COVID-19; Effectiveness; Molnupiravir; Nirmatrelvir/ritonavir.

Fig. 1

Flowchart of patient inclusion and exclusion

Fig. 2

Unadjusted cumulative incidence curves with risk tables for selected outcomes (outcomes ascertained from day 31 to day 365, unless otherwise specified)

Fig. 3

Effects of the antivirals on each outcome after weighting (the hazard ratios for the time intervals of Day 0–30 and Day 31–365 were derived from separate Cox proportional hazards models). Outcomes were ascertained from Day 31 to Day 365, unless otherwise specified. The axis is in logarithmic scale. (A): Comparison between the nirmatrelvir/ritonavir group and control group. (B): Comparison between the molnupiravir group and control group. (C): Comparison between the nirmatrelvir/ritonavir group and molnupiravir group. N/R: nirmatrelvir/ritonavir