GSK, Stevenage, United Kingdom.
GSK, Brentford, United Kingdom.
Elife. 2024 Feb 7;13:e89263. doi: 10.7554/eLife.89263.
A single 300 mg dose of tafenoquine, in combination with chloroquine, is currently approved in several countries for the radical cure (prevention of relapse) of malaria in patients aged ≥16 years. Recently, however, Watson et al. suggested that the approved dose of tafenoquine is insufficient for radical cure, and that a higher 450 mg dose could reduce P. vivax recurrences substantially (Watson et al., 2022). In this response, we challenge Watson et al.'s assertion based on empirical evidence from dose-ranging and pivotal studies (published) as well as real-world evidence from post-approval studies (ongoing, therefore currently unpublished). We assert that, collectively, these data confirm that the benefit-risk profile of a single 300 mg dose of tafenoquine, co-administered with chloroquine, for the radical cure of malaria in patients who are not G6PD-deficient, continues to be favourable where chloroquine is indicated for malaria. If real-world evidence of sub-optimal efficacy in certain regions is observed or dose-optimisation with other blood-stage therapies is required, then well-designed clinical studies assessing safety and efficacy will be required before higher doses are approved for clinical use.
单次 300 毫克剂量的他非诺喹与氯喹联合使用，目前在多个国家被批准用于治疗年龄≥16 岁的疟疾患者的根治（预防复发）。然而，最近 Watson 等人提出，他非诺喹的批准剂量不足以根治，更高的 450 毫克剂量可大大减少间日疟原虫的复发（Watson 等人，2022 年）。在本次回应中，我们基于剂量范围和关键研究（已发表）以及批准后研究的真实世界证据（正在进行，因此目前未发表）对 Watson 等人的观点提出质疑。我们断言，这些数据共同证实，对于没有 G6PD 缺乏症的疟疾患者，在氯喹适用的情况下，联合氯喹使用单次 300 毫克剂量的他非诺喹进行根治的获益风险状况仍然是有利的。如果在某些地区观察到实际疗效不理想的证据，或者需要与其他血期疗法进行剂量优化，则需要进行精心设计的临床研究，评估安全性和疗效，然后才能批准更高剂量用于临床使用。
