背景:ADAGEN®,基于牛的酶替代疗法(ERT)已被用于治疗腺苷脱氨酶严重联合免疫缺陷(ADA-SCID).2018年,ADAGEN®被REVCOVI®取代,(elapegademase)一种修饰的牛重组蛋白。
目的:确定REVCOVI®在ADA-SCID中的实际长期益处。
方法:ERT上的数据,感染性和非感染性并发症,从17个ADA-SCID治疗6个月或更长时间的REVCOVI®收集代谢和免疫评价。
结果:11例患者先前接受ADAGEN®治疗16至324个月,而6例患者未接受ERT治疗。REVCOVI®在ERT-Naive中以0.4mg/kg/周每周两次给药,虽然从ADAGEN®过渡到REVCOVI®的患者通常以与ADAGEN®相同的频率和等效剂量继续进行,导致过渡组的REVCOVI®总剂量显着降低(p=0.007)。REVCOVI®在ERT-na-ive组治疗导致了ADA缺乏的许多临床和实验室并发症的解决,而在过渡患者中,没有新的不良反应.REVCOVI®治疗在大多数患者中增加血浆ADA活性并降低dAXP,在整个7-37个月的治疗期间持续的效果,除了2例依从性不完全的患者。在一些患者中,0.5到6个月后,注射频率减少到每周一次,同时保持足够的代谢谱。所有接受REVCOVI®治疗的未接受ERT治疗的婴儿均表现出CD4+T和CD19+B细胞数量增加,尽管在大多数过渡患者中,这些计数保持稳定,但低于正常。
结论:REVCOVI®对于ADA-SCID的管理是有效的。
ADAGEN, a bovine-based enzyme replacement therapy (ERT), has been used to treat adenosine deaminase severe combined immunodeficiency (ADA-SCID). In 2018, ADAGEN was replaced by REVCOVI (elapegademase), a modified bovine recombinant protein.
To determine the real-life long-term benefits of REVCOVI in ADA-SCID.
Data on ERT, infectious and noninfectious complications, and metabolic and immune evaluations were collected from 17 patients with ADA-SCID treated for 6 months or more with REVCOVI.
Eleven patients had previously received ADAGEN for 16 to 324 months, whereas 6 patients were ERT-naive. REVCOVI was administered twice weekly at 0.4 mg/kg/wk in ERT-naive patients, whereas patients transitioning to REVCOVI from ADAGEN typically continued at the same frequency and equivalent dosing as ADAGEN, resulting in a significantly lower (P = .007) total REVCOVI dose in the transitioning group. REVCOVI treatment in the ERT-naive group led to the resolution of many clinical and laboratory complications of ADA deficiency, whereas there were no new adverse effects among the transitioning patients. REVCOVI treatment increased plasma ADA activity and decreased dAXP (which included deoxyadenosine mono-, di-, and tri phosphate) among most patients, effects that persisted throughout the 7- to 37-month treatment periods, except in 2 patients with incomplete adherence. Among some patients, after 0.5 to 6 months, injection frequency was reduced to once a week, while maintaining adequate metabolic profiles. All ERT-naive infants treated with REVCOVI demonstrated an increase in the number of CD4+ T and CD19+ B cells, although these counts remained stable but lower than normal in most transitioning patients.
REVCOVI is effective for the management of ADA-SCID.