协会Lonafarnib治疗与不治疗的患者死亡率Hutchinson-Gilford早衰症综合征。

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戈登磅,Shappell H,马萨罗J, RB达Sr,火盆J,坎贝尔,Kleinman我,基兰兆瓦

协会Lonafarnib治疗与不治疗的患者死亡率Hutchinson-Gilford早衰症综合征。

《美国医学协会杂志》上。2018年4月24日,319 (16):1687 - 1695。doi: 10.1001 / jama.2018.3264。

PubMed ID

29710166 (在PubMed

]

文摘

重要性:Hutchinson-Gilford早衰症综合征(hgp)是一种极其罕见的致命疾病过早老化。没有批准的治疗。摘要目的:评价单一疗法协会使用蛋白质治疗抑制剂lonafarnib计的儿童死亡率。设计、设置和参与者:队列研究比较的(出生日期> / = 1991)患者治疗计画与治疗患者按年龄,性别,和使用条件Cox比例风险回归居住的大陆。治疗组中患者2单一群体,单临床试验(ProLon1 [n = 27个;完成]和ProLon2 [n = 36;正在进行的)。未经治疗的病人来自一个单独的自然历史研究(n = 103)。患者随访截止日期是1月1日,2018年。曝光:患者口服lonafarnib (150 mg / m2)每天两次。 Untreated patients received no clinical trial medications. Main Outcomes and Measures: The primary outcome was mortality. The primary analysis compared treated patients from the first lonafarnib trial with matched untreated patients. A secondary analysis compared the combined cohorts from both lonafarnib trials with matched untreated patients. Results: Among untreated and treated patients (n = 258) from 6 continents, 123 (47.7%) were female; 141 (54.7%) had a known genotype, of which 125 (88.7%) were classic (c.1824C>T in LMNA). When identified (n = 73), the primary cause of death was heart failure (79.4%). The median treatment duration was 2.2 years. Median age at start of follow-up was 8.4 (interquartile range [IQR], 4.8-9.5) years in the first trial cohort and 6.5 (IQR, 3.7-9.0) years in the combined cohort. There was 1 death (3.7%) among 27 patients in the first trial group and there were 9 deaths (33.3%) among 27 patients in the matched untreated group. Treatment was associated with a lower mortality rate (hazard ratio, 0.12; 95% CI, 0.01-0.93; P = .04). In the combined cohort, there were 4 deaths (6.3%) among 63 patients in the treated group and 17 deaths (27.0%) among 63 patients in the matched untreated group (hazard ratio, 0.23; 95% CI, 0.06-0.90; P = .04). Conclusions and Relevance: Among patients with HGPS, lonafarnib monotherapy, compared with no treatment, was associated with a lower mortality rate after 2.2 years of follow-up. Study interpretation is limited by its observational design.

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药物

Lonafarnib