Drugs for Neglected Diseases Initiative (DNDi), Geneva, Switzerland.
Malar J. 2012 Jan 25;11:25. doi: 10.1186/1475-2875-11-25.
Artesunate-amodiaquine (AS&AQ) is a widely used artemisinin combination therapy (ACT) for falciparum malaria. A comprehensive appreciation of its effects on haematology vs other anti-malarials is needed in view of potential safety liabilities.
Individual-patient data analysis conducted on a database from seven randomized controlled trials conducted in sub-Saharan African comparing AS&AQ to reference treatments in uncomplicated falciparum malaria patients of all ages. Haematologic values (white cells total and neutrophil counts, haemoglobin/haematocrit, platelets) were analysed as both continuous and categorical variables for their occurrence, (severity grade 1-4) and changes during follow-up. Risks and trends were calculated using multivariate logistic random effect models.
4,502 patients (72% < 5 years old), from 13 sites in nine countries with 28-day follow-up were treated with AS&AQ (45%) or a comparator (other forms of ACT accounted for 27%, other combination 12%, mono-therapies 16%). Pre-treatment leucopaenia (3%) and neutropaenia (6%) were infrequent; anaemia was common (39%). The treatment-emergent adverse events incidence (TEAE = condition not present or less severe pre-treatment) was 11% for neutropaenia, 6% for thrombocytopaenia with AS&AQ and not different from treatment groups; anaemia was higher with AS&AQ (20%) or other forms of ACT (22%) than in non-artemisinin groups (4%, p = 0.001). Multivariate analysis showed that the risk of anaemia, thrombocytopaenia, and leucopaenia decreased with follow-up time, while neutropaenia increased; the risk of anaemia and thrombocytopaenia increased with higher baseline parasitaemia and parasitological reappearance. White cells total count was not a good surrogate for neutropaenia. No systematic significant difference between treatments was detected. Older patients were at lower risks.
The effects of AS&AQ on haematologic parameters were not different from those of other anti-malarial treatments used in sub-Saharan Africa. This analysis provides the basis for a broader evaluation of haematology following anti-malarial treatment. Continuing monitoring of haematologic safety on larger databases is required.
青蒿琥酯-阿莫地喹（AS&AQ）是一种广泛使用的青蒿素类复方疗法（ACT），用于治疗恶性疟原虫疟疾。鉴于潜在的安全风险，需要全面了解其对血液学的影响与其他抗疟药物的差异。
对来自撒哈拉以南非洲地区的 7 项随机对照试验的数据库进行个体患者数据分析，比较 AS&AQ 与其他参考治疗方案在所有年龄段的无并发症恶性疟原虫患者中的疗效。血液学值（白细胞总数和中性粒细胞计数、血红蛋白/血细胞比容、血小板）以连续性和分类变量的形式进行分析，以评估其发生（严重程度 1-4 级）和随访期间的变化。使用多变量逻辑随机效应模型计算风险和趋势。
4502 名患者（72%年龄<5 岁）来自 9 个国家的 13 个地点，随访 28 天，接受 AS&AQ（45%）或对照治疗（其他形式的 ACT 占 27%，其他联合疗法占 12%，单一疗法占 16%）。治疗前白细胞减少症（3%）和中性粒细胞减少症（6%）并不常见；贫血较为常见（39%）。治疗后出现的不良事件发生率（TEAE=治疗前不存在或症状较轻）为中性粒细胞减少症 11%，血小板减少症 6%，AS&AQ 与其他治疗组之间无差异；贫血在 AS&AQ（20%）或其他形式的 ACT（22%）组中高于非青蒿素组（4%，p=0.001）。多变量分析显示，贫血、血小板减少症和白细胞减少症的风险随随访时间的延长而降低，而中性粒细胞减少症的风险则增加；基线寄生虫载量和寄生虫学再现越高，贫血和血小板减少症的风险越高。白细胞总数不能很好地替代中性粒细胞减少症。未发现治疗组之间存在系统的显著差异。年龄较大的患者风险较低。
AS&AQ 对血液学参数的影响与在撒哈拉以南非洲地区使用的其他抗疟药物治疗无差异。本分析为更广泛地评估抗疟治疗后的血液学提供了基础。需要在更大的数据库中继续监测血液学安全性。
