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Luspatercept治疗输血依赖性β地中海贫血可显著降低输血负担
作者:小柯机器人 发布时间:2020/3/29 23:56:32

意大利米兰大学Domenica Cappellini课题组在研究中取得进展。他们探讨了Luspatercept治疗输血依赖型β地中海贫血患者的疗效。该研究成果发表在2020年3月26日出版的《新英格兰医学杂志》上。

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,可结合选择转化生长因子β超家族配体,增强患者的红系成熟并减少输血负担。

在这项随机、双盲、3期临床试验中,研究组招募患有输血依赖型β地中海贫血的成年人,在最优支持治疗的基础上,按2:1随机分组,224名患者接受Luspatercept治疗,112名接受安慰剂治疗,至少48周。

两组患者中位治疗了64周。治疗第12-24周,Luspatercept组中输液负担比基线降低至少33%,且该时间段内至少减少了2个红细胞单位的患者所占百分比为21.4%,显著高于安慰剂组(4.5%),差异具有统计学意义。

在任何12周的时间间隔内,Luspatercept组中输血负担降低至少33%和至少50%的患者百分比分别为70.5%和40.2%,均显著高于安慰剂组(29.5%和6.3%)。治疗第48周,两组血清铁蛋白水平的最小二乘均值差为-348μg/升,倾向于Luspatercept组。但与安慰剂组相比,Luspatercept组更容易发生短暂性骨痛、关节痛、头晕、高血压和高尿酸血症等不良事件。

总之,Luspatercept治疗输血依赖性β-地中海贫血患者,与安慰剂相比,可显著降低输血负担,且几乎没有导致停药的不良事件发生。

附:英文原文

Title: A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia

Author: M. Domenica Cappellini, M.D.,, Vip Viprakasit, D.Phil.,, Ali T. Taher, M.D., Ph.D.,, Pencho Georgiev, M.D.,, Kevin H.M. Kuo, M.D.,, Thomas Coates, M.D.,, Ersi Voskaridou, M.D.,, Hong-Keng Liew, M.B., B.S.,, Idit Pazgal-Kobrowski, M.D.,, G.L. Forni, M.D.,, Silverio Perrotta, M.D.,, Abderrahim Khelif, M.D.,, Ashutosh Lal, M.D.,, Antonis Kattamis, M.D., Ph.D.,, Efthymia Vlachaki, M.D., Ph.D.,, Raffaella Origa, M.D.,, Yesim Aydinok, M.D.,, Mohamed Bejaoui, M.D.,, P. Joy Ho, M.B., B.S., D.Phil.,, Lee-Ping Chew, M.D.,, Ping-Chong Bee, M.D.,, Soo-Min Lim, M.D.,, Meng-Yao Lu, M.D.,, Adisak Tantiworawit, M.D.,, Penka Ganeva, M.D.,, Liana Gercheva, M.D., Ph.D.,, Farrukh Shah, M.B., B.S.,, Ellis J. Neufeld, M.D., Ph.D.,, Alexis Thompson, M.D., M.P.H.,, Abderrahmane Laadem, M.D.,, Jeevan K. Shetty, M.B., Ch.B.,,, Jun Zou, M.D., Ph.D.,, Jennie Zhang, M.S.,, Dimana Miteva, Ph.D.,, Tatiana Zinger, Ph.D.,, Peter G. Linde, M.D.,, Matthew L. Sherman, M.D.,, Olivier Hermine, M.D., Ph.D.,, John Porter, M.D.,, and Antonio Piga, M.D.

Issue&Volume: 2020-03-25

Abstract: AbstractBackground

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.

DOI: NJ202003263821308

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1910182

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home