Hepatic safety of repeated treatment with pyronaridine‐artesunate versus artemether–lumefantrine in patients with uncomplicated malaria: a secondary analysis of the WANECAM 1 data from Bobo-Dioulasso, Burkina Faso

• Published in: Malaria Journal
• Main Authors: Yves Daniel Compaoré, Issaka Zongo, Anyirékun F. Somé, Nouhoun Barry, Frederick Nikiéma, Talato N. Kaboré, Aminata Ouattara, Zachari Kabré, Kadidiatou Wermi, Moussa Zongo, Rakiswende S. Yerbanga, Issaka Sagara, Abdoulaye Djimdé, Jean Bosco Ouédraogo
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2021
• Subjects: Repeated treatment; Pyronaridine‐artesunate; Artemether–lumefantrine; Uncomplicated malaria; Hepatoxicity; Hy’s law; Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/s12936-021-03593-6; https://doaj.org/article/d2c1961a61fe440dabc36493799e36dd

Abstract Background The use of pyronaridine-artesunate (PA) has been associated with scarce transaminitis in patients. This analysis aimed to evaluate the hepatic safety profile of repeated treatment with PA versus artemether–lumefantrine (AL) in patients with consecutive uncomplicated malaria episodes in Bobo-Dioulasso, Burkina Faso. Methods This study analysed data from a clinical trial conducted from 2012 to 2015, in which participants with uncomplicated malaria were assigned to either PA or AL arms and followed up to 42 days. Subsequent malaria episodes within a 2-years follow up period were also treated with the same ACT initially allocated. Transaminases (AST/ALT), alkaline phosphatase (ALP), total and direct bilirubin were measured at days 0 (baseline), 3, 7, 28 and on some unscheduled days if required. The proportions of non-clinical hepatic adverse events (AEs) following first and repeated treatments with PA and AL were compared within study arms. The association of these AEs with retreatment in each arm was also determined using a logistic regression model. Results A total of 1379 malaria episodes were included in the intention to treat analysis with 60% of all cases occurring in the AL arm. Overall, 179 non-clinical hepatic AEs were recorded in the AL arm versus 145 in the PA arm. Elevated ALT was noted in 3.05% of treated malaria episodes, elevated AST 3.34%, elevated ALP 1.81%, and elevated total and direct bilirubin in 7.90% and 7.40% respectively. Retreated participants were less likely to experience elevated ALT and AST than first episode treated participants in both arms. One case of Hy’s law condition was recorded in a first treated participant of the PA arm. Participants from the retreatment group were 76% and 84% less likely to have elevated ALT and AST, respectively, in the AL arm and 68% less likely to present elevated ALT in the PA arm. In contrast, they were almost 2 times more likely to experience elevated total bilirubin in both arms. Conclusions Pyronaridine-artesunate and ...