BACKGROUND Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.).

中文翻译：

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输血依赖性β-地中海贫血患者中Luspatercept的3期试验。

背景技术输血依赖型β地中海贫血患者需要定期输注红细胞。Luspatercept是一种重组融合蛋白，可与选择的转化生长因子β超家族配体结合，可增强此类患者的红系成熟并减少输血负担（输血的红细胞单位总数）。方法在这项随机，双盲，3期临床试验中，我们以2：1的比例分配患有输血依赖型β地中海贫血的成年人，以接受最佳支持治疗和luspatercept（剂量为每公斤1.00至1.25 mg体重）或安慰剂至少48周。主要终点是在第13周到第24周内与基线相比输血负担减少至少33％的患者百分比，以及在这12周间隔内减少至少2个红细胞单位的患者百分比。其他功效终点包括在任何12周间隔内减少输血负荷和铁研究的结果。结果总共有224名患者被分配到luspatercept组，而112名被分配到安慰剂组。两组均接受Luspatercept或安慰剂治疗，中位数约为64周。在13周至24周内，输液负担比基线减少至少33％，并且在这12周间隔内减少了至少2个红细胞单位的患者百分比在luspatercept组中明显高于在安慰剂组（21.4％vs. 4.5％，P <0.001）。在任何12周的时间间隔内，luspatercept组的输血负担降低至少33％的患者百分比高于安慰剂组（分别为70.5％和29.5％），减少了至少50％的人所占的百分比（40.2％对6.3％）。两组之间血清铁蛋白水平的最小二乘均方差为-348微克/升（95％置信区间，-517至-179），有利于接受luspatercept。Luspatercept较安慰剂更常见短暂性骨痛，关节痛，头晕，高血压和高尿酸血症的不良事件。结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）两组之间血清铁蛋白水平的最小二乘均方差为-348微克/升（95％置信区间，-517至-179），有利于接受luspatercept。Luspatercept较安慰剂更常见短暂性骨痛，关节痛，头晕，高血压和高尿酸血症的不良事件。结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）两组之间血清铁蛋白水平的最小二乘均方差为-348微克/升（95％置信区间，-517至-179），有利于接受luspatercept。Luspatercept较安慰剂更常见短暂性骨痛，关节痛，头晕，高血压和高尿酸血症的不良事件。结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）-517至-179）赞成luspatercept。Luspatercept较安慰剂更常见短暂性骨痛，关节痛，头晕，高血压和高尿酸血症的不良事件。结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）-517至-179）赞成luspatercept。Luspatercept较安慰剂更常见短暂性骨痛，关节痛，头晕，高血压和高尿酸血症的不良事件。结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）结论在输液负担减轻的输血依赖型β地中海贫血患者中，卢斯帕汀组的发生率明显高于安慰剂组，并且几乎没有不良事件导致停止治疗。（由Celgene和Acceleron Pharma资助; BELIEVE ClinicalTrials.gov编号，NCT02604433; EudraCT编号，2015-003224-31。）