Ataga Kenneth I
Center for Sickle Cell Disease, University of Tennessee Health Science Center, Memphis, TN.
Blood. 2023 Dec 14;142(24):2047-2054. doi: 10.1182/blood.2023021220.
As most patients with sickle cell disease (SCD) do not have access to curative therapies, the availability of drug therapies that can modify disease severity remains highly desirable. Despite an increased understanding of the pathophysiology of SCD, only 4 drugs are approved by the US Food and Drugs Administration. Most drug trials in SCD have involved the use of acute pain episodes as the primary clinical end point. These studies have typically been to prevent or shorten the duration of such episodes. To date, no drug has received regulatory approval for shortening the duration of acute vaso-occlusive complications, likely highlighting the complex pathophysiology of acute pain episodes. Trials to prevent acute pain episodes have largely evaluated those episodes requiring health care use as a surrogate end point. However, with differences in culture and health care practices among countries, health care use may not reliably predict clinically important effects on acute pain episodes. This article discusses issues related to the use of health care use as the primary end point for prevention trials of acute pain episodes and highlights the importance of evaluating patient-reported outcomes as well as other SCD-related complications as outcome measures.
由于大多数镰状细胞病（SCD）患者无法获得治愈性疗法，因此能够改善疾病严重程度的药物疗法仍然非常值得期待。尽管对SCD的病理生理学有了更多了解，但美国食品药品监督管理局仅批准了4种药物。SCD的大多数药物试验都将急性疼痛发作作为主要临床终点。这些研究通常旨在预防或缩短此类发作的持续时间。迄今为止，尚无药物获得缩短急性血管闭塞性并发症持续时间的监管批准，这可能凸显了急性疼痛发作复杂的病理生理学。预防急性疼痛发作的试验主要评估那些需要医疗护理的发作，并将其作为替代终点。然而，由于各国文化和医疗保健实践存在差异，医疗护理的使用可能无法可靠地预测对急性疼痛发作的临床重要影响。本文讨论了将医疗护理的使用作为急性疼痛发作预防试验主要终点的相关问题，并强调了评估患者报告的结局以及将其他与SCD相关的并发症作为结局指标的重要性。
