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

Abstract

Background: We provided a comprehensive evaluation of efficacy of available treatments for coronavirus disease 2019 (COVID-19).Methods: We searched for candidate COVID-19 studies in WHO COVID-19 Global Research Database up to August 19, 2021. Randomized controlled trials for suspected or confirmed COVID-19 patients published on peer-reviewed journals were included, regardless of demographic characteristics. Outcome measures included mortality, mechanical ventilation, hospital discharge and viral clearance. Bayesian network meta-analysis with fixed effects was conducted to estimate the effect sizes using posterior means and 95% equal-tailed credible intervals (CrIs). Odds ratio (OR) was used as the summary measure for treatment effect. Bayesian hierarchical models were used to estimate effect sizes of treatments grouped by the treatment classifications.Results: We identified 222 eligible studies with a total of 102,950 patients. Compared with the standard of care, imatinib, intravenous immunoglobulin and tocilizumab led to lower risk of death; baricitinib plus remdesivir, colchicine, dexamethasone, recombinant human granulocyte colony stimulating factor and tocilizumab indicated lower occurrence of mechanical ventilation; tofacitinib, sarilumab, remdesivir, tocilizumab and baricitinib plus remdesivir increased the hospital discharge rate; convalescent plasma, ivermectin, ivermectin plus doxycycline, hydroxychloroquine, nitazoxanide and proxalutamide resulted in better viral clearance. From the treatment class level, we found that the use of antineoplastic agents was associated with fewer mortality cases, immunostimulants could reduce the risk of mechanical ventilation and immunosuppressants led to higher discharge rates.Conclusions: This network meta-analysis identified superiority of several COVID-19 treatments over the standard of care in terms of mortality, mechanical ventilation, hospital discharge and viral clearance. Tocilizumab showed its superiority compared with SOC on preventing severe outcomes such as death and mechanical ventilation as well as increasing the discharge rate, which might be an appropriate treatment for patients with severe or mild/moderate illness. We also found the clinical efficacy of antineoplastic agents, immunostimulants and immunosuppressants with respect to the endpoints of mortality, mechanical ventilation and discharge, which provides valuable information for the discovery of potential COVID-19 treatments.

Systematic Review and Meta-Analysis of Ivermectin for Treatment of COVID-19: Evidence Beyond the Hype

“…Only two studies were included in the pooled analysis to assess mortality and mechanical ventilation requirement [28]. As aforementioned, a recent network meta-analysis has shown how different statistical approaches (random vs. xed) lead to different results on the effects of ivermectin on viral clearance [15].…”

“…When authors analyzed the data using a xed effects model approach, there was a signi cant effect of ivermectin on reducing viral clearance (OR 2.32, 95% equal-tailed credible intervals [CrIs] 1.38 -3.94); this effect was nonsigni cant when they used a random effects model approach (OR 2.70, 95% CrI [1.24, 6.12]), [15] demonstrating how choosing or not the proper methods for analysis can in uence the results.…”

Meta-Analyses Do Not Establish Improved Mortality With Ivermectin Use in COVID-19

“…13 We have identified 17 metaanalyses concluding HCQ/CQ increased mortality in COVID-19, potentially worsening control outcomes, and overstating ivermectin's efficacy. [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] Only 3 metaanalyses indicated reduced mortality with HCQ/CQ, potentially favoring control outcomes. [41][42][43] Importantly, the Food and Drug Administration and European Medicines Agency recommend using active controls that are standard of care and already approved for the studied indication which is not the case for HCQ/CQ.…”

Multipurpose Drugs Active Against Both Plasmodium spp. and Microorganisms: Potential Application for New Drug Development

“…The proposed mechanism of action against these viruses is through inhibition of nuclear transport mediated by the importin a/b1 heterodimer (Wagstaff et al, 2011;Wagstaff et al, 2012b). Though most of the studies of antiviral activities of ivermectin were based on assessments with in vitro assays, some studies on its effect on SARS-CoV-2 patient treatment were performed based on a small-scale clinical trial (Pott-Junior et al, 2021;Zhang et al, 2021) or meta-analyses of the publications and databases (Deng et al, ;Cruciani et al, 2021) about its effects on prophylaxis or prognosis of the treatments, which were mixed in terms of the efficacy of the drug on its clinical use and none was conclusive, along with negative results with in vitro study (Dinesh Kumar et al, 2021), stressing the need for more studies about its clinical application.…”