Comparison of Efficacy and Safety of Artemisinin-Based Combination Therapies for Treating Uncomplicated Falciparum Malaria in Sub-Saharan African Countries: An Update on the Changes in Efficacy Using Network Meta-Analysis

Abstract

Background: Several artemisinin-based combination therapies (ACT) are available to treat uncomplicated malaria in Africa. The present study aimed to assess the ranking of their efficacy and tolerance. Methods: A database of randomized controlled trials was retrieved from published papers. Network meta-analysis was used to compare efficacy on day 28 and day 42 after initiation of treatment. Age covariate effect on treatment outcome was assessed, and a modeling approach to reduce heterogeneity among trials was evaluated under the hypothesis of consistency in a meta-regression. Safety and adverse events were compared among different ACTs. A Bayesian analysis was performed to implement the consistency models using WinBUGS software. The results were compared to those of the frequentist approach using the R software. Results: Eighty-one articles, in which a total of 15 different ACTs were tested in more than 36,000 patients, were included. On day 28, dihydroartemisinin-piperaquine (DHPP) was more effective than artemether-lumefantrine (AL) before (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.31 - 2.56) and after age-covariate adjustment (OR, 1.70; 95% CI, 1.20 - 2.43). The result was similar on day 42. DHPP occupied the top rank. The risk of having cough, diarrhoea or headache post-treatment was significantly lower with DHPP than AL. Artesunate-mefloquine (ASMQ) was associated with a significantly lower prevalence of vomiting or nausea (OR, 0.80; 95% CI, 0.48 - 1.30) and headache (OR, 0.53; 95% CI, 0.40 - 0.68) compared to AL. On the contrary, vomiting and nausea occurred more frequently after fixed-dose artesunate-amodiaquine formulation (ASAQf) than with AL (OR, 1.45; 95% CI, 1.18 - 1.78). The risk of anaemia was higher with ASAQf and co-blistered artesunate-amodiaquine (ASAQc) than with AL. There was no significant difference in risk of anaemia (P > 0.05) between AL and different formulations of ASAQ. Conclusions: Based on the available evidence, this study demonstrated the superiority of DHPP, followed by AL, among currently recommended ACTs in terms of efficacy and tolerance. Network meta-analysis could be an alternative analytical tool but needs more data input from therapeutic efficacy studies. The determination of the best available therapy requires data triangulation and data science.