Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis.
Comprehensive long-term efficacy and safety of recombinant human alpha-mannosidase (velmanase alfa) treatment in patients with alpha-mannosidosis.
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DOI：
10.1007/s10545-018-0175-2
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发表时间：
2018-11
影响因子：
4.2
通讯作者：
Guffon N
中科院分区：
文献类型：
--
作者：
Lund AM;Borgwardt L;Cattaneo F;Ardigò D;Geraci S;Gil-Campos M;De Meirleir L;Laroche C;Dolhem P;Cole D;Tylki-Szymanska A;Lopez-Rodriguez M;Guillén-Navarro E;Dali CI;Héron B;Fogh J;Muschol N;Phillips D;Van den Hout JMH;Jones SA;Amraoui Y;Harmatz P;Guffon N
长期结果数据为酶替代疗法的临床应用提供了重要的见解。在治疗α-甘露糖苷症(AM)中，维拉曼酶α-阿法提供了这样的数据。患者数据(n = 33；14成人，19儿科)从魏尔曼酶阿尔法的临床开发计划中被整合到这项前瞻性设计的长期有效性和安全性分析中。参加I/II期或III期试验并在试验完成后继续接受治疗的患者被邀请参加全面评估访问，以评估长期结果。主要观察指标为血清低聚糖和3分钟爬楼梯试验(3MSCT)。平均(SD)治疗暴露29.3(15.2)个月。总体人群的血清低聚糖水平在12个月后显著降低(平均变化：-72.7%，P <； 0.001)，并在最后一次观察时仍具有统计学意义(−62.8%，P <； 0.001)。在12个月时，3MSCT的平均改善为+9.3%(P = 0.013)，在最后一次观察时仍有统计学意义(+13.8%，P = 0.004)，其中儿科亚组的改善更为显著。没有报告治疗突发不良事件导致永久停止治疗。接受魏尔曼酶α治疗的患者在生化和功能指标方面有所改善，这些指标可维持长达4年。长期随访是重要的，并进一步支持使用维拉曼酶α作为AM的有效和耐受性良好的治疗方法。根据目前可用的数据集，没有基线特征可以预测治疗结果。在儿科年龄早期治疗在功能终点显示出更好的结果。本文的在线版本(10.1007/s10545-0180175-2)包含补充材料，可供授权用户使用。
Long-term outcome data provide important insights into the clinical utility of enzyme replacement therapies. Such data are presented for velmanase alfa in the treatment of alpha-mannosidosis (AM). Patient data (n = 33; 14 adults, 19 paediatric) from the clinical development programme for velmanase alfa were integrated in this prospectively-designed analysis of long-term efficacy and safety. Patients who participated in the phase I/II or phase III trials and were continuing to receive treatment after completion of the trials were invited to participate in a comprehensive evaluation visit to assess long-term outcomes. Primary endpoints were changes in serum oligosaccharide and the 3-minute stair climb test (3MSCT). Mean (SD) treatment exposure was 29.3 (15.2) months. Serum oligosaccharide levels were significantly reduced in the overall population at 12 months (mean change: –72.7%, P < 0.001) and remained statistically significant at last observation (−62.8%, P < 0.001). A mean improvement of +9.3% in 3MSCT was observed at 12 months (P = 0.013), which also remained statistically significant at last observation (+13.8%, P = 0.004), with a more pronounced improvement detected in the paediatric subgroup. No treatment-emergent adverse events were reported leading to permanent treatment discontinuation. Patients treated with velmanase alfa experienced improvements in biochemical and functional measures that were maintained for up to 4 years. Long term follow-up is important and further supports the use of velmanase alfa as an effective and well-tolerated treatment for AM. Based on the currently available data set, no baseline characteristic can be predictive of treatment outcome. Early treatment during paediatric age showed better outcome in functional endpoints. The online version of this article (10.1007/s10545-018-0175-2) contains supplementary material, which is available to authorized users.
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影响因子：
3.8
作者：
Tajima, Go;Sakura, Nobuo;Kobayashi, Masao
通讯作者：
Kobayashi, Masao
影响因子：
120.7
作者：
Meikle, PJ;Hopwood, JJ;Carey, WF
通讯作者：
Carey, WF
影响因子：
3.6
作者：
Malm, D;Halvorsen, DS;Sjursen, H
通讯作者：
Sjursen, H
影响因子：
8
作者：
Meikle, PJ;Ranieri, E;Hopwood, JJ
通讯作者：
Hopwood, JJ
影响因子：
4.8
作者：
Mynarek, M.;Tolar, J.;Sykora, K-W
通讯作者：
Sykora, K-W