Comparative Effectiveness of Pharmacological Interventions for Covid-19: A Systematic Review and Network Meta-Analysis

Abstract

Background: Several pharmacological interventions are now under investigation for the treatment of Covid-19, and the evidence is evolving rapidly. Our aim is to assess the comparative efficacy and safety of these drugs.Methods and Findings: We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We performed a systematic review and network meta-analysis searching Medline, Pubmed, Embase, Cochrane Covid-19 register, international trial registers, medRxiv, bioRxiv, and arXiv up to December 10, 2020. We included all randomised controlled trials (RCTs) comparing any pharmacological intervention for Covid-19 against any drugs, placebo or standard care (SC). Data extracted from published reports were assessed for risk of bias in accordance with the Cochrane tool, and using the GRADE framework. Primary outcomes were all-cause mortality, adverse events (AEs) and serious adverse events (SAEs). We estimated summary risk ratio (RR) using pairwise and network meta-analysis with random effects (Prospero, number CRD42020176914). We included 96 RCTs, comprising of 34,501 patients. The network meta-analysis showed in terms of all-cause mortality, when compared to SC or placebo, only corticosteroids significantly reduced the mortality rate (RR 0.90, 95%CI 0.83, 0.97; moderate certainty of evidence). Corticosteroids significantly reduced the mortality rate also when compared to hydroxychloroquine (RR 0.83, 95%CI 0.74, 0.94; moderate certainty of evidence). Remdesivir proved to be better in terms of SAEs when compared to SC or placebo (RR 0.75, 95%CI 0.63, 0.89; high certainty of evidence) and plasma (RR 0.57, 95%CI 0.34, 0.94; high certainty of evidence). The combination of lopinavir and ritonavir proved to reduce SAEs when compared to plasma (RR 0.49, 95%CI 0.25, 0.95; high certainty of evidence). Most of the RCTs were at unclear risk of bias (42 of 96), one third were at high risk of bias (34 of 96) and 20 were at low risk of bias. Certainty of evidence ranged from high to very low.Conclusion: At present, corticosteroids reduced all-cause mortality in patients with Covid-19, with a moderate certainty of evidence. Remdesivir appeared to be a safer option than SC or placebo, while plasma was associated with safety concerns. These preliminary evidence-based observations should guide clinical practice until more data are made public.

Efficacy of COVID-19 Treatments: A Bayesian Network Meta-Analysis of Randomized Controlled Trials

“…In addition, we mainly focused on the efficacy of interventions in this NMA and did not evaluate the corresponding safety profiles. Evidence from other NMAs ( 7 , 179 ) showed that most of investigated treatments in this NMA did not lead to increased adverse events, and remdesivir and lopinavir/ritonavir were associated with fewer occurrences of adverse events and serious adverse events, respectively.…”

Activation of Sphingomyelinase-Ceramide-Pathway in COVID-19 Purposes Its Inhibition for Therapeutic Strategies

“…The data from our study close the gap between retrospective observations by presenting a potential mechanism of ASM release and action in COVID-19 patients. Keeping the paucity of proven host-directed therapies in mind, the low level of evidence of the majority of all running trials (14,99) and due to the fact that a panel of FDA-approved drugs with low risk of adverse effects is awaiting consequent investigation, the potential usefulness of antidepressants in patients with COVID-19 taking FIASMA for other indications with now known guiding principles should be prioritized for RCT and can minimize the risk of being exposed to novel, potentially harmful of ineffective compounds or compounds with unknown mode of action. As also recommended by others, the results support the continuation of FIASMA medication in these patients (69).…”

Efficacy of Convalescent Plasma to Treat Mild to Moderate COVID-19 in Kidney Transplant Patients: A Propensity Score Matching Analysis

“…Kidney transplant recipients have higher mortality from coronavirus disease 2019 (COVID-19) compared with the general population. 1 , 2 In the absence of effective treatment, 3 the early use of convalescent plasma emerged as an alternative therapy with a favorable safety profile.…”