A meta-analysis of artemisinin-based combination therapies (ACTs) reveals changes in therapeutic efficacy

Abstract

Artemisinin-based combination therapies (ACTs) are recommended by WHO for treatment of uncomplicated P.falciparum malaria. In clinical trials, differences in efficacy are recorded due to resistance of the parasites. In the previous meta-analysis published, artemether + lumefantrine (AL) was ranked first based on the efficacy parameter cure rate at day 28, PCR corrected. PubMed was searched to retrieve all trials published before March 2010 containing the key words 'artesunate', 'artemether' or 'dihydroartemisinin'. Trials were acceptable for analysis if they pertained to a randomized controlled clinical trial and evaluated the clinical efficacy of one or more of the following therapies: artemether + lumefantrine (AL), artesunate + amodiaquine (AS+AQ), artesunate + sulfadoxine (AS+SP), artesunate + mefloquine (AS+MQ), artesunate + sulfamethoxypyrazine-pyrimethamine (AS + SMP) or dihydroartemisinin + piperaquine (DHA + PQ) for treatment of uncomplicated P. falciparum malaria. Ninety-two randomized clinical trials were included in a multi-treatment Bayesian random effects meta-analysis, calculating the posterior median for the odds ratio (OR) of cure rates in the corresponding treatments over the baseline treatment AL. In addition, a direct comparison was performed to grade the different treatments without taking into account the heterogeneity of the studies. Bayesian random effects meta-analysis did not detect any statistically significant difference between the ACTs. The cure rate of AS + SMP (posterior median of OR 1.2; 95% CI, 0.42, 6.5) was found to be equally effective as AL in the treatment of malaria. While the direct comparison should be interpreted cautiously AS+ SMP was found to be significantly better than AL. Therapeutic efficacy of ACTs changes over time. The current analysis reveals changes in the relative drug efficacy value and proposes artesunate + sulfamethoxypyrazine-pyrimethamine (AS+SMP) as alternative treatment. Apart from efficacy, other factors are important in the overall evaluation of ACTs namely, the ease of administration, cost price, side effects and pharmaceutical stability.