Case Laura E, Bjartmar Carl, Morgan Claire, Casey Robin, Charrow Joel, Clancy John P, Dasouki Majed, DeArmey Stephanie, Nedd Khan, Nevins Mary, Peters Heidi, Phillips Dawn, Spigelman Zachary, Tifft Cynthia, Kishnani Priya S
Duke University Medical Center, Durham, North Carolina, USA.
Genzyme, a sanofi company, Cambridge, Massachusetts, USA.
Neuromuscul Disord. 2015 Apr;25(4):321-32. doi: 10.1016/j.nmd.2014.12.004. Epub 2014 Dec 19.
Emerging phenotypes in long-term survivors with Pompe disease on standard enzyme replacement therapy (ERT) (alglucosidase alfa 20 mg/kg/2 weeks) can include patients with worsening motor function. Whether higher doses of ERT improve skeletal function in these patients has not been systematically studied. This exploratory, randomized, open-label, 52-week study examined the safety and efficacy of 2 ERT regimens of alglucosidase alfa (20 mg/kg/week or 40 mg/kg/2 weeks) in 13 patients with Pompe disease and clinical decline or a lack of improvement on standard ERT: late-onset (n = 4), infantile-onset (n = 9). Cross-reactive immunologic material assay-negative patients were excluded. Eleven of 13 patients completed the study. Trends for improvement were seen in total gross motor function, but not mobility; however, 6 (late-onset, 2; infantile-onset, 4) of 11 patients (55%) who met the entry criteria of motor decline (late-onset, 4; infantile-onset, 7) showed improvement in motor and/or mobility skills. No between-regimen differences in efficacy emerged. Two case studies highlight the benefits of increased ERT dose in patients with Pompe disease experiencing clinical decline. Both alternative regimens were generally well tolerated. This study was limited by the small sample size, which is not uncommon for small clinical studies of rare diseases. Additionally, the study did not include direct assessment of muscle pathology, which may have identified potential causes of decreased response to ERT. Results were inconclusive but suggest that increased ERT dose may be beneficial in some patients with Pompe disease experiencing motor decline. Controlled studies are needed to clarify the benefits and risks of this strategy.
接受标准酶替代疗法（ERT）（阿糖苷酶α，20mg/kg/每2周）的庞贝病长期存活者中出现的新表型可能包括运动功能恶化的患者。更高剂量的ERT是否能改善这些患者的骨骼功能尚未得到系统研究。这项探索性、随机、开放标签、为期52周的研究，在13例庞贝病患者且临床病情恶化或接受标准ERT治疗后无改善的患者中，研究了阿糖苷酶α的两种ERT方案（20mg/kg/每周或40mg/kg/每2周）的安全性和有效性：迟发型（n = 4）、婴儿型（n = 9）。交叉反应免疫物质检测阴性的患者被排除。13例患者中有11例完成了研究。总粗大运动功能有改善趋势，但活动能力无改善；然而，符合运动功能下降纳入标准的11例患者（55%）（迟发型，2例；婴儿型，4例）中有6例（迟发型，4例；婴儿型，7例）运动和/或活动能力有所改善。不同治疗方案之间未出现疗效差异。两个病例研究突出了增加ERT剂量对临床病情恶化的庞贝病患者的益处。两种替代方案总体耐受性良好。本研究受样本量小的限制，这在罕见病的小型临床研究中并不少见。此外，该研究未包括对肌肉病理学的直接评估，而这可能已确定了对ERT反应降低的潜在原因。结果尚无定论，但表明增加ERT剂量可能对一些运动功能下降的庞贝病患者有益。需要进行对照研究以阐明该策略的益处和风险。
