Safety and effectiveness of recombinant factor XIII-A(2) in congenital factor XIII deficiency: Real-world evidence

重组因子 XIII-A(2)治疗先天性因子 XIII 缺乏症的安全性和有效性:真实世界证据

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Abstract

BACKGROUND: Regular factor XIII (FXIII) prophylaxis is standard treatment for congenital FXIII A-subunit deficiency (FXIII-A CD). Recombinant factor XIII-A(2) (rFXIII-A(2)) was extensively evaluated in the mentor trials. OBJECTIVE: To assess real-world safety and treatment effectiveness of rFXIII-A(2) prophylaxis from the mentor 6 trial. PATIENTS/METHODS: mentor 6 was a noninterventional, postauthorization safety study investigating rFXIII-A(2) prophylaxis in FXIII-A CD. rFXIII-A(2) treatment was observed for 2 to 6 years per patient. The primary end point was documentation of adverse drug reactions (including anti-FXIII antibody development). Secondary end points were serious adverse events (SAEs), medical events of special interest (MESIs), and annualized bleeding rate (ABR). RESULTS: Among 30 patients (mean age, 25.5 years), there were 44 adverse events (AEs) (30 mild, 13 moderate, 1 severe). Eleven AEs were possibly/probably related to rFXIII-A(2). Of four MESIs, two were unlikely related to rFXIII-A(2) (accidental overdose, deep vein thrombosis), and two were possibly/probably related (nonneutralizing anti-FXIII antibody, decreased therapeutic response). All 10 SAEs were unlikely related to rFXIII-A(2). Over a follow-up of 75.4 patient-years, there were six treatment-requiring bleeds (all trauma-related with no spontaneous bleeds), giving a treatment-requiring ABR of 0.066; five bleeds were treated successfully with rFXIII-A(2). Eight of nine minor surgeries performed during rFXIII-A(2) prophylaxis reported successful hemostatic outcomes (one missing evaluation). CONCLUSIONS: These data confirm that rFXIII-A(2) prophylaxis is well tolerated as long-term care. There were no spontaneous bleeds, ABR was low, and rFXIII-A(2) successfully treated bleeds in patients receiving rFXIII-A(2) prophylaxis.

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