洛那法尼治疗与未治疗与Hutchinson-Gilford早衰综合征患者死亡率的关系
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Gordon LB, Shappell H, Massaro J, D'Agostino RB Sr, Brazier J, Campbell SE, Kleinman ME, Kieran MW
洛那法尼治疗与未治疗与Hutchinson-Gilford早衰综合征患者死亡率的关系
《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。
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29710166 (PubMed视图]
- 摘要
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重要性:哈钦森-吉尔福德早衰综合征(HGPS)是一种极其罕见的致死性早衰疾病。目前尚无批准的治疗方法。目的:评价蛋白法尼基转移酶抑制剂lonafarnib单药治疗与HGPS患儿死亡率的关系。设计、环境和参与者:队列研究比较同期(出生日期>/=1991)未治疗的HGPS患者与按年龄、性别和居住地区进行匹配的治疗患者，采用条件Cox比例风险回归。治疗队列包括来自2个单组、单点临床试验的患者(ProLon1 [n = 27;completed]和ProLon2 [n = 36;正在进行的)。未经治疗的患者来自一项独立的自然史研究(n = 103)。患者随访截止日期为2018年1月1日。暴露:治疗患者接受口服洛那法尼(150mg /m2)，每日两次。 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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