背景:脂蛋白脂肪酶(LPL)缺乏,一种罕见的遗传性代谢紊乱,其特征在于高甘油三酯(TG)水平和危及生命的急性胰腺炎。目前儿科患者的治疗包括终身严格限制脂肪的饮食,提出坚持挑战。Volanesorsen,EMA批准的成人RNA疗法,通过减少载脂蛋白C-III的产生有效降低TG水平。这项为期96周的观察性开放标签研究探讨了Volanesorsen在患有LPL缺乏症的13岁女性中的安全性和有效性。
方法:患者,有严重的TG升高史,53住院,和危及生命的复发性胰腺炎,尽管饮食限制,每周皮下注射Volanesorsen.我们为这项研究者发起的研究设计了一个方案,主要关注空腹TG水平和入院率的变化。
结果:虽然注射引起偶尔的疼痛和肿胀,未观察到其他不良事件.治疗期间TG水平下降,与治疗前相比,更多的测量值低于胰腺炎风险阈值。在最初14个月的治疗中没有住院,与96周前的21次入院形成鲜明对比。在过去的10个月里,两次胰腺炎发作可能与饮食不依从性有关.放宽了饮食限制,与基线相比,脂肪摄入量增加65%。虽然没有充分反映在PedsQL中,父母和患者均叙述了生活质量的改善.
结论:这项研究表明,第一次,Volanesorsen在患有严重LPL缺乏症的儿科患者中具有耐受性,并有效降低TG水平,预防危及生命的并发症。这需要考虑扩大这一人群的准入。
BACKGROUND: Lipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen\'s safety and efficacy in a 13-year-old female with LPL deficiency.
METHODS: The patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions.
RESULTS: While the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life.
CONCLUSIONS: This study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.