Clinical Data Supporting the Use of Non-Fixed AS + AQ Association and the Fixed-Dose ASAQ Combination
Non-fixed association of AS+AQ: Supporting data from 37 studies
Information on the efficacy and safety of the non-fixed AS+AQ association is available from a total of 37 studies, involving approximately 10,000 patients who received AS + AQ in various drugs’ ratios.
Evidence of the safety of the sanofi-aventis AS + AQ combination is available from a number of studies. In the largest study, performed in Senegal in over 3,000 patients, no adverse events requiring in-patient hospitalisation were reported 1. The most commonly reported adverse events possibly related to treatment were vomiting (5.6%), pruritus (3.8%) and dizziness (3.1%). It is important to mention that some patients had been complaining of vomiting and/or dizziness prior to the treatment, as often seen in malaria attacks.
The most comprehensive review of efficacy of the non-fixed AS+AQ association was recently conducted by Olliaro and al. 2 who performed a meta-analysis of 30 studies, published and unpublished, conducted with AS+AQ in various drug ratios during 1999-2006. Out of these 30 studies, 27 were comparative versus other ACT or single products, and 3 were non comparative. The efficacy studies enrolled 11,751 patients, including 5,272 patients who received AS+AQ. Overall, AS+AQ was found to be more effective than single agent treatment or non artemisinin based combinations. AS+AQ Day 28 cure rates after PCR correction were similar to other ACTs. Safety data were not reported uniformly across all studies. AS+AQ was found to be “well tolerated”, and the incidence of vomiting, the most commonly reported event, was similar between AS+AQ and other treatments.
Fixed-dose ASAQ: An efficacious and well-tolerated new treatment
The fixed-dose combination was tested in one study to date, carried out in Burkina Faso, comparing the fixed-dose ASAQ combination to the loose AS+AQ association. This study included 750 children between 6 and 59 months old, with uncomplicated falciparum malaria. No significant difference was seen between the efficacy of both presentations, based on the PCR-corrected parasite clearance at Day 28, irrespective of the analysis method used (intent–to-treat or per protocol). The analysis of the most clinically relevant population shows cure rates of 95.7% for the fixed-dose ASAQ combination and 96% for the loose-dose combination. The incidence of general adverse events was consistent with what can be expected for young patients presenting with malaria. It is difficult to assign reports of fatigue, nausea, vomiting to the study drugs, the malaria infection itself or to concomitant conditions. Based on what is known of AS and AQ safety profile, no unexpected adverse events occurred during this study.
1. Artesunate (AS) plus amodiaquine (AQ) for treating falciparum malaria – assessing its efficacy and tolerability during six years of field deployment in Southern Senegal. Brasseur Ph et al. ASTMH Atlanta Nov 2006; abstract 306.
2. P. Olliaro, M. Vaillant, R. Phalkey, J. Guthmann, G. Dorsey, P. Brasseur, et al. Artesunate + Amodiaquine (AS+AQ) for the treatment of uncomplicated falciparum malaria: an inventory of clinical studies and systematic review of safety and efficacy data. Abstracts of the American Society of Tropical Medicine and Hygiene 55th Annual Meeting, Atlanta November 12-16, 2006. Abstract.n°307: Am J Trop Med Hyg 2006; 75 (Supplement 5).
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