Artesunate-amodiaquine therapy linked to lower Ebola mortality

1. Artesunate-amodiaquine (AA) treated Ebola patients had a significantly lower risk of death than artemether-lumefantrine (AL) treated patients.

2. The effect reduced mortality associated with AA treatment in comparison to AL was attenuated when the study population was stratified a positive malaria test.

Evidence Rating Level: 2 (Good)  

Study Rundown: Since the outbreak of Ebola virus disease (EVD) in West Africa back in March 2014, the FDA has approved several artemisinin-based antimalarial drugs that have demonstrated in vitro anti-EVD activity. In this retrospective cohort study, researchers analyzed patient data from an Ebola treatment center in Foya, Liberia. Per protocol, patients diagnosed with EVD at the center were treated with prophylactic antibiotics and a 3-day course of AL, an antimalarial therapy. However, in August 2014, the center experienced a temporary shortage of AL, and patients were alternatively prescribed a 3-day course of AA – a therapy that is sometimes recommended as second-line to AL due to amodiaquine’s potential hepatotoxicity when used as long-term prophylaxis. In this retrospective cohort study, researchers analyzed mortality rates between patients prescribed AA and AL, finding a significantly lower risk of death in the AA group compared to the AL group. However, this effect was not significant when patients were stratified by positive malaria status. The data in this study are limited by possible temporal-related differences between AA vs. AL groups, as patients in the two groups were admitted at different times. Other limitations acknowledged by the authors included lack of data on patient completion of full drug regimen. Overall, this study suggests that AA may provide more protection against mortality than AL.

Click to read the study, published today in NEJM

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In-Depth [retrospective cohort]: In this retrospective cohort study, a total of 382 patients (one excluded for lack of outcome data) were categorized into four groups: EVD patients prescribed AL, AA, no antimalarials or EVD patients with no prescription information. Mortality was higher in the AL group versus the AA group (64.6% vs. 51%). In an analysis adjusted for potential confounding factors, the AA group had a 31% lower risk of death compared to the AL group (RR=0.69, 95%[CI]=0.54-0.89). After stratifying mortality between AA and AL groups based on malaria diagnosis, the authors found no difference in adjusted mortality risk in patients positive for malaria (RR=1.0, 95%[CI]=0.54-1.85, p=0.98). However, there was a significantly lower adjusted mortality risk between the AA and AL group in patients that tested negative for malaria (RR=0.64, 95%[CI]=0.63-1.01, p=0.06). However, in patients with a positive malaria status, treatment with any antimalarial agent reduced the risk of mortality compared to no antimalarial treatment at all. 

Image: PD

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