Biegstraaten Marieke, Arngrímsson Reynir, Barbey Frederic, Boks Lut, Cecchi Franco, Deegan Patrick B, Feldt-Rasmussen Ulla, Geberhiwot Tarekegn, Germain Dominique P, Hendriksz Chris, Hughes Derralynn A, Kantola Ilkka, Karabul Nesrin, Lavery Christine, Linthorst Gabor E, Mehta Atul, van de Mheen Erica, Oliveira João P, Parini Rossella, Ramaswami Uma, Rudnicki Michael, Serra Andreas, Sommer Claudia, Sunder-Plassmann Gere, Svarstad Einar, Sweeb Annelies, Terryn Wim, Tylki-Szymanska Anna, Tøndel Camilla, Vujkovac Bojan, Weidemann Frank, Wijburg Frits A, Woolfson Peter, Hollak Carla E M
Department of Internal Medicine, Division Endocrinology and Metabolism, Academic Medical Center, PO Box 22660, Amsterdam, 1100 DD, The Netherlands.
Biomedical Center, University of Iceland and Landspitali University Hospital, Reykjavík, Iceland.
Orphanet J Rare Dis. 2015 Mar 27;10:36. doi: 10.1186/s13023-015-0253-6.
Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD.
A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75% agreement and no disagreement.
For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m(2)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped.
The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.
法布里病(FD)是一种溶酶体贮积症,可导致进行性神经系统、肾脏和心脏疾病。酶替代疗法(ERT)可能会阻止或减缓疾病进展。由于给药负担重且费用高昂,因此必须合理使用。我们旨在确定欧洲关于FD患者ERT起始和停止的共识性建议。
采用德尔菲法,进行了一项在线调查(n = 28)和一次会议(n = 15)。患者组织代表出席了会议以发表意见。建议以≥75%的同意率且无反对意见获得通过。
对于典型受累男性,达成的共识是,一旦出现肾脏、心脏或脑部受累的早期临床体征,就建议开始ERT,但在无器官受累临床体征或症状的16岁及以上患者中也可考虑使用。典型受累女性和非典型FD男性,一旦出现肾脏、心脏或脑部受累的早期临床体征,就应接受治疗,而对于具有被认为是由FD导致的早期临床体征的非典型FD女性,可考虑进行治疗。达成的共识是,对于严重肾功能不全(肾小球滤过率<45 ml/min/1.73 m²)、接受透析或有认知功能下降的患者,不应停止治疗,但应在个体基础上仔细考虑。对于终末期FD或其他合并症导致预期寿命<1年的患者,可考虑停止ERT。对于任何原因导致认知功能下降的患者,或当ERT的唯一指征是神经性疼痛且1年无反应时,可考虑停止ERT。此外,对于终末期肾病且无肾移植选择并合并晚期心力衰竭(纽约心脏病协会IV级)的患者,应考虑停止ERT。对于不依从或未定期就诊的患者,应停止ERT。
这些建议可作为ERT起始和停止的基准,尽管最终决策应在个体基础上做出。未来需要开展合作努力以优化这些建议。