Hematology-Oncology, Pediatric Specialists of Virginia, Fairfax, Virginia, USA.
Division of Cardiology, Children's National Hospital, Washington, District of Columbia, USA.
Pediatr Blood Cancer. 2023 Aug;70(8):e30423. doi: 10.1002/pbc.30423. Epub 2023 May 29.
Individuals with sickle cell anemia (SCA) exhibit decreased exercise capacity. Anemia limits oxygen-carrying capacity and affects cardiopulmonary fitness. The drug voxelotor raises hemoglobin in SCA. We hypothesized that voxelotor improves exercise capacity in youths with SCA.
In a single-center, open-label, single-arm, longitudinal interventional pilot study (NCT04581356), SCA patients aged 12 and older, stably maintained on hydroxyurea, were treated with 1500 mg voxelotor daily, and performed cardiopulmonary exercise testing before (CPET#1) and after voxelotor (CPET#2). A modified Bruce Protocol was performed on a motorized treadmill, and breath-by-breath gas exchange data were collected. Peak oxygen consumption (peak VO ), anaerobic threshold, O pulse, VE/VCO slope, and time exercised were compared for each participant. The primary endpoint was change in peak VO . Hematologic parameters were measured before each CPET. Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) surveys were collected.
Ten hemoglobin SS patients aged 12-24 completed the study. All demonstrated expected hemoglobin rise, with average +1.6 g/dL (p = .003) and P left shift of average -11 mmHg (p < .0001) with decreased oxygen off-loading at low pO . The change in % predicted peak VO from CPET#1 to CPET#2 ranged from -12.8% to +11.3%, with significant improvement of more than 5% in one subject, more than 5% decrease in five subjects, and insignificant change of less than 5% in four subjects. All 10 CGIC and seven of 10 PGIC responses were positive.
In a plot study of 10 youths with SCA, voxelotor treatment did not improve peak VO in 9 out of 10 patients.
镰状细胞贫血（SCA）患者的运动能力下降。贫血会降低携氧能力，并影响心肺健康。药物沃替拉生可提高 SCA 患者的血红蛋白水平。我们假设沃替拉生可提高 SCA 青少年的运动能力。
在一项单中心、开放标签、单臂、纵向干预性研究（NCT04581356）中，年龄在 12 岁及以上、稳定接受羟基脲治疗的 SCA 患者每日服用 1500mg 沃替拉生，并在服用沃替拉生之前（CPET#1）和之后（CPET#2）进行心肺运动测试。在电动跑步机上进行改良的布鲁斯方案，同时采集逐口气体交换数据。比较每位参与者的峰值耗氧量（peak VO ）、无氧阈、O 脉冲、VE/VCO 斜率和运动时间。主要终点为 peak VO 的变化。每次 CPET 前均测量血液学参数。收集患者总体印象变化（PGIC）和医生总体印象变化（CGIC）调查结果。
10 名血红蛋白 SS 型患者（年龄 12-24 岁）完成了该研究。所有患者均表现出预期的血红蛋白升高，平均升高 1.6g/dL（p=0.003），pO 降低时左移平均-11mmHg（p<0.0001），低氧脱负荷减少。CPET#1 到 CPET#2 的%预测峰值 VO 的变化范围为-12.8%至+11.3%，其中一名患者的改善超过 5%，五名患者的下降超过 5%，四名患者的变化不超过 5%。10 名 CGIC 和 7 名 PGIC 患者的反应均为阳性。
在 10 名 SCA 青少年的病例研究中，沃替拉生治疗并未使 10 名患者中的 9 名的 peak VO 得到改善。
