Revel-Vilk Shoshana, Ramaswami Uma, Pintos-Morell Guillem, Hughes Derralynn, Nicholls Kathy, Reisin Ricardo, Giugliani Roberto, Goker-Alpan Ozlem, Istaiti Majdolen, Gill Aidan, Scarpa Maurizio, Botha Jaco
Gaucher Unit and Pediatric Hematology/Oncology Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel.
Faculty of Medicine, Hebrew University, Jerusalem, Israel.
Orphanet J Rare Dis. 2025 Mar 28;20(1):145. doi: 10.1186/s13023-024-03416-2.
Fabry disease and Gaucher disease are rare genetic disorders characterized by defective degradation of glycosphingolipids caused by enzymatic deficiencies in α-galactosidase A and β-glucocerebrosidase, respectively, and often require life-long treatment. Treatment options for these disorders include replacing the deficient enzymes via enzyme replacement therapy (ERT). Agalsidase alfa for Fabry disease and velaglucerase alfa for Gaucher disease are two ERT options with demonstrated efficacy, safety, and tolerability. ERT infusions administered by a health care provider (HCP) in the clinic/hospital, or at the patient's home are considered HCP-supported infusions. Self-administration of ERT (by patient, partner, relative, or caregiver) is optional in patients who tolerate the HCP-supported infusions at home and have a suitable home environment. This analysis explored the safety profiles of self-administered agalsidase alfa (202 patients) and velaglucerase alfa (30 patients) versus HCP-supported infusions using data from the Fabry Outcome Survey (FOS) and Gaucher Outcome Survey (GOS) registries.
The frequency of infusion-related reactions (IRRs) adverse events (AEs) recorded in the two registries was lower in patients self-administering (FOS: 4.5%, GOS: 0%) versus patients receiving HCP-supported infusions (FOS: 13.6%, GOS: 1.6%). In the FOS registry, AE rates per 100 patient-years (100PY) of follow-up were similar between the self-administration (7.99) and HCP-supported infusion (6.78) groups. In patients self-administering agalsidase alfa, cardiac disorders were the most frequently reported AEs (19 [9.4%] patients) and serious AEs (12 [5.9%]) and gastrointestinal disorders were the most frequently reported IRRs (3 [1.5%]). In the GOS registry, AE rates per 100PY were similar between self-administration (4.97) and HCP-supported infusion (4.67) groups. In patients self-administering velaglucerase alfa, skin and subcutaneous disorders (4 [13.3%]) and infections and infestations (2 [6.7%]) were the most reported AEs and serious AEs, respectively, and no IRRs were reported.
These findings suggest that self-administration of agalsidase alfa or velaglucerase alfa infusions are not associated with additional safety risks compared with HCP-supported infusions and are a suitable option for qualifying patients. Further research is warranted to support these findings and to explore further the long-term safety and efficacy of ERT self-administration. FOS trial registration: ClinicalTrials.gov, NCT03289065. Registered 01 April 2001, https://clinicaltrials.gov/study/NCT03289065 . GOS trial registration: ClinicalTrials.gov, NCT03291223. Registered 27 July 2010, https://classic.
gov/ct2/show/NCT03291223 .
法布里病和戈谢病是罕见的遗传性疾病，分别由α-半乳糖苷酶A和β-葡萄糖脑苷脂酶的酶缺陷导致糖鞘脂降解缺陷，通常需要终身治疗。这些疾病的治疗选择包括通过酶替代疗法（ERT）补充缺乏的酶。用于法布里病的阿加糖酶α和用于戈谢病的维拉苷酶α是两种已证明具有疗效、安全性和耐受性的ERT选择。由医疗保健提供者（HCP）在诊所/医院或患者家中进行的ERT输注被视为HCP支持的输注。对于在家中耐受HCP支持的输注且有合适家庭环境的患者，ERT的自我给药（由患者、伴侣、亲属或护理人员进行）是可选的。本分析利用法布里病结局调查（FOS）和戈谢病结局调查（GOS）登记处的数据，探讨了自我给药的阿加糖酶α（202例患者）和维拉苷酶α（30例患者）与HCP支持的输注相比的安全性概况。
在两个登记处记录的输注相关反应（IRR）不良事件（AE）的发生率，自我给药的患者（FOS：4.5%，GOS：0%）低于接受HCP支持输注的患者（FOS：13.6%，GOS：1.6%）。在FOS登记处，自我给药组（7.99）和HCP支持输注组（6.78）每100患者年（100PY）的AE发生率相似。在自我给药阿加糖酶α的患者中，心脏疾病是最常报告的AE（19例[9.4%]患者）和严重AE（12例[5.9%]），胃肠道疾病是最常报告的IRR（3例[1.5%]）。在GOS登记处，自我给药组（4.97）和HCP支持输注组（4.67）每100PY的AE发生率相似。在自我给药维拉苷酶α的患者中，皮肤和皮下疾病（4例[13.3%]）和感染与寄生虫病（2例[6.7%]）分别是最常报告的AE和严重AE，未报告IRR。
这些发现表明，与HCP支持的输注相比，自我给药阿加糖酶α或维拉苷酶α输注不会带来额外的安全风险，对于符合条件的患者是一个合适的选择。有必要进行进一步的研究来支持这些发现，并进一步探索ERT自我给药的长期安全性和疗效。FOS试验注册：ClinicalTrials.gov，NCT03289065。2001年4月1日注册，https://clinicaltrials.gov/study/NCT03289065 。GOS试验注册：ClinicalTrials.gov，NCT03291223。2010年7月27日注册，https://classic.
gov/ct2/show/NCT03291223 。
