Patterson Marc C, Mengel Eugen, Vanier Marie T, Schwierin Barbara, Muller Audrey, Cornelisse Peter, Pineda Mercè
Department of Neurology, Mayo Clinic, 200 first Street SW, Rochester, MN, 55905, USA.
Villa Metabolica, University of Mainz, Mainz, Germany.
Orphanet J Rare Dis. 2015 May 28;10:65. doi: 10.1186/s13023-015-0284-z.
Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat.
The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit.
In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data.
Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.
尼曼-匹克病C型（NP-C）是一种罕见的神经内脏疾病，其特征为进行性神经退行性变，神经疾病进展速度因神经症状出现时的年龄而异。我们报告了国际NPC注册中心接受米格鲁司他持续治疗的患者功能疾病进展和安全性观察的纵向数据。
NPC注册中心是一个NP-C患者的前瞻性观察队列。本分析纳入了接受≥1年米格鲁司他持续治疗（观察期的≥90%，单次治疗中断不超过28天）的入组患者。使用一个从0（正常）到1（最差）对行走、操作、语言和吞咽四个领域进行评分的量表来测量残疾情况。基于以下两点对所有患者的神经疾病进展进行分析：1）入组至末次随访期间的年进展率；2）分类分析，若入组至末次随访期间≥3/4个领域的评分降低/未改变，则将患者分类为“改善/稳定”，若<3个领域的评分降低/未改变，则分类为“进展”。
2009年9月至2013年10月期间，共有来自13个欧洲国家、加拿大和澳大利亚28个中心的283例患者入组；92例患者接受了米格鲁司他持续治疗。观察期（入组至末次随访）内米格鲁司他的平均（标准差）暴露时间为2.0（0.7）年。在84例可评估患者中，9例（11%）神经症状出现于婴儿早期（<2岁），27例（32%）出现于婴儿晚期（2至<6岁），30例（36%）出现于青少年期（6至<15岁），18例（21%）出现于青少年/成人期（≥15岁）。所有患者入组时的平均（95%CI）综合残疾评分为0.37（0.32，0.42），末次随访时为0.44（0.38，0.50），平均年进展率为0.038（0.018，0.059）。综合残疾评分的进展在婴儿期或儿童期出现神经症状的患者中似乎最高，在青少年/成人期出现神经症状的患者中最低。总体而言，86例可评估患者中有59例（69%）被分类为改善/稳定，且改善/稳定患者的比例随神经症状出现时的年龄增加而增加。安全性结果与既往数据一致。
在平均接受2年米格鲁司他持续治疗的大多数患者中，残疾状况得到改善/稳定。
