This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.

To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID‐19). PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID‐19 outpatients were included. The Cochrane risk‐of‐bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID‐19‐related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19–0.36; I² = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17−0.34; I² = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05−0.58; I² = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64–1.01; I² = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19–0.72; I² = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID‐19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.

The aim of this meta-analysis is to compare the clinical efficacy and safety of baloxavir with other anti-influenza agents or placebo in the treatment of influenza. PubMed, Embase, Web of Science, Google Scholar, Scopus, CINAHL, Cochrane databases and clinical registration were searched from inception until February 15 2021 for relevant randomized controlled trials (RCTs). Only phase 3 RCTs evaluating the usefulness of baloxavir in the treatment of influenza were included. Three RCTs enrolling 3771 patients (baloxavir group, n = 1451; oseltamivir group, n = 1288; placebo group, n = 1032) were included. Compared with oseltamivir, baloxavir had an insignificantly shorter time to the alleviation of symptoms (mean difference [MD], -1.29 h; 95% CI, -6.80 to 4.21; I² = 0%). In contrast, baloxavir had a significantly shorter time to the alleviation of symptoms than placebo (MD, -26.32 h; 95% CI, -33.78 to -18.86; I² = 0%). Baloxavir was associated with a significant decline in influenza virus titers and viral RNA load compared to oseltamivir and placebo. Baloxavir was associated with a lower risk of any adverse events than oseltamivir (OR, 0.82; 95% CI, 0.69-0.98; I² = 0%) and placebo (OR, 0.79; 95% CI, 0.66-0.96; I² = 0%). The findings of this meta-analysis suggested that baloxavir is superior to placebo in the treatment of influenza in both clinical outcome and virological response. Moreover, baloxavir was found to have a better virological response than oseltamivir and to be as effective as oseltamivir clinically. Compared with oseltamivir and placebo, baloxavir appears to be a relatively safe anti-influenza agent.

Introduction: Nintedanib can inhibit processes involved in the progression of fibrosis and can reduce the decline in forced vital capacity in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic-interstitial lung disease (fibrotic-ILDs). Although the adverse events associated with nintedanib in IPF patients are well known, its safety in other fibrotic-ILD patients remained unclear. Methods: We searched PubMed, EMBASE, Cochrane CENTRAL and Cochrane CDSR for randomized controlled studies which compared nintedanib with a placebo in ILD patients. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs) for adverse events using the DerSimonian–Laird random-effects model. Results: Six studies with a total of 2,583 patients were included in the meta-analysis. The pooled estimates showed that patients treated with nintedanib had a significantly higher likelihood of having any adverse events (OR = 2.39; 95% CI = 1.71–3.36) or adverse events leading to treatment discontinuation (OR = 1.73; 95% CI = 1.34–2.25). However, they had trend to lower likelihood of having fatal adverse events (OR = 0.69; 95% CI = 0.41–1.14) compared with the placebo group. Use of nintedanib was positively associated with diarrhea (OR = 5.96; 95% CI = 4.35–8.16), nausea (OR = 3.00; 95% CI = 1.93–4.66), vomiting (OR = 3.22; 95% CI = 2.17–4.76) and weight loss (OR = 3.38; 95% CI = 1.1.76–6.47). Whereas, patients treated with nintedanib were less likely to have a cough (OR = 0.73; 95% CI = 0.56–0.96) and dyspnea (OR = 0.70; 95% CI = 0.53–0.94). Conclusions: Compared to a placebo, nintedanib was associated with a higher risk of adverse events, especially for diarrhea, nausea, vomiting and weight loss, but it was also associated with a lower risk of cough and dyspnea in IPF and fibrotic-ILD patients.

The aim of this study was to investigate the clinical efficacy and safety of cefiderocol in the treatment of acute bacterial infections. The PubMed, Embase and Cochrane Library databases as well as the clinical trials registries of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched up to 8 November 2020. Only randomised controlled trials (RCTs) that compared the treatment efficacy of cefiderocol with that of other antibiotics for adult patients with acute bacterial infections were included in this meta-analysis. The primary outcome was clinical response at test of cure (TOC). Three RCTs, including one phase 2 and two phase 3 trials, were included. No significant difference in clinical response rate was observed between cefiderocol and comparators [odds ratio (OR)=1.04]. In a subgroup analysis, no significant difference was observed in the clinical response at TOC between cefiderocol and comparators in patients with nosocomial pneumonia (OR=0.92) or complicated urinary tract infection (OR=1.28). In addition, all-cause mortality at Days 14 and 28 did not differ between the cefiderocol and control groups (14-day mortality, OR=1.25; 28-day mortality, OR=1.12). Furthermore, cefiderocol was associated with similar microbiological response to comparators at the TOC assessment (OR=1.44). Finally, cefiderocol was associated with a similar risk of adverse events as comparators. Cefiderocol can achieve similar clinical and microbiological responses as comparators for patients with serious bacterial infections. In addition, cefiderocol shares a safety profile similar to that of comparators.