Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia
Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with β-thalassemia
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DOI：
10.1016/j.clinthera.2007.05.007
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发表时间：
2007-05-01
影响因子：
3.2
通讯作者：
Baladi, Jean-Francois
中科院分区：
文献类型：
--
作者：
Cappellini, Maria Domenica;Bejaoui, Mohamed;Baladi, Jean-Francois
背景资料：使用去铁胺（DFO）的铁螯合疗法（ICT）是治疗输血依赖性疾病（如β-地中海贫血）患者铁过载的当前标准，需要定期皮下或静脉输注。这可能导致生活质量降低和依从性差，导致铁超载的β-地中海贫血患者的发病率和死亡率增加。地拉罗司是一种口服铁螯合剂，已被批准在美国，瑞士和其他countries.Objective：本分析旨在比较接受DFO输注或每日一次口服地拉罗司（ICL 670）治疗期间的患者报告结局（PRO）。作为随机、前瞻性评估的一部分，在患者中比较DFO 20 - 60 mg/kg/天与地拉罗司5 - 30 mg/kg/天的疗效和安全性特征的III期研究（年龄>= 2岁）患有β-地中海贫血，接受定期输血，肝脏铁浓度>= 2 mg/g干重。在基线、第4周、第24周和研究结束（EOS）时，由患者或父母或法律的监护人完成PRO问卷。患者评估其对研究治疗的满意度（非常满意、满意、中性、不满意或非常不满意），并对其便利性进行评分（非常方便、方便、中性、不方便或非常不方便）。使用单一全球评估记录了过去4周因信通技术而损失的正常活动时间。在第4周，要求既往有DFO经历的患者说明他们对研究前接受的治疗（JCT、研究期间接受的ICT、无偏好或无应答）的偏好以及偏好的原因。在EOS，询问所有患者是否愿意继续使用研究期间接受的ICT。所有的研究分析中进行的所有患者接受至少1剂的研究medication.Results：586例患者（304名女性，282名男性;年龄范围，2-53岁）接受治疗DFO（n = 290）或地拉罗司（n = 296）。与DFO治疗的患者相比，地拉罗司治疗的患者报告非常满意或满意治疗的患者明显更多（第4周：92.0% vs 50.4%;第24周：89.6% vs 44.0%; EOS：85.1% vs 38.7%;所有，P < 0.001）。在相同的时间点，大多数接受地拉罗司治疗的患者报告与接受DFO治疗的患者相比，治疗非常方便或方便（分别为95.5% vs 21.3%，91.7% vs 17.4%和92.7% vs 11.3%;均P < 0.001）。在先前服用DFO并在研究期间随机接受地拉罗司的患者中，96.9%的患者报告偏好地拉罗司而不是DFO。在EOS时，接受地拉罗司的患者中表示愿意继续研究治疗的患者比例显著高于接受DFO的患者（85.8% vs 13.8%; P < 0.001）。结论：在本研究中，每日一次口服ICT地拉罗司的患者报告满意度和便利性显著高于DFO输注。在研究前接受DFO的患者中，大多数人表示偏好地拉罗司而不是DFO。大多数接受地拉罗司的患者表示他们愿意继续服用，这些结果表明地拉罗司对患者的日常生活有积极的影响。
Background: Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries.Objective: This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670).Methods: PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age >= 2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of >= 2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment JCT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication.Results: Five hundred eighty-six patients (304 females, 282 males; age range, 2-53 years) received treatment with DFO (n = 290) or deferasirox (n = 296). Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO (week 4: 92.0% vs 50.4%, respectively; week 24: 89.6% vs 44.0%; EOS: 85.1% vs 38.7%; all, P < 0.001). At the same time points, the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO (95.5% vs 21.3%, 91.7% vs 17.4%, and 92.7% vs 11.3%, respectively; all, P < 0.001). Among patients who had previously taken DFO and were randomized to receive deferasirox during the study, 96.9% reported a preference for deferasirox over DFO. At EOS, the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO (85.8% vs 13.8%; P < 0.001).Conclusions: In this study, patient-reported satisfaction and convenience were significantly higher for the once-daily, oral ICT deferasirox than for DFO infusions. Among patients who had received DFO before the study, the majority indicated a preference for deferasirox over DFO. Most patients receiving deferasirox indicated that they would be willing to continue taking it. These results suggest that deferasirox had a positive impact on patients' daily lives.