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. 2022 Feb 27;6(2):e12628.
doi: 10.1002/rth2.12628. eCollection 2022 Feb.

Safety and effectiveness of recombinant factor XIII-A2 in congenital factor XIII deficiency: Real-world evidence

Lone Hvitfeldt Poulsen  1 , Bryce A Kerlin  2 , Giancarlo Castaman  3 , Angelo Claudio Molinari  4 , Marzia Menegatti  5 , Diane Nugent  6 , Sohan Dey  7 , May-Lill Garly  8 , Manuel Carcao  9
Affiliations

Safety and effectiveness of recombinant factor XIII-A2 in congenital factor XIII deficiency: Real-world evidence

Lone Hvitfeldt Poulsen et al. Res Pract Thromb Haemost. .

Abstract

Background: Regular factor XIII (FXIII) prophylaxis is standard treatment for congenital FXIII A-subunit deficiency (FXIII-A CD). Recombinant factor XIII-A2 (rFXIII-A2) was extensively evaluated in the mentor trials.

Objective: To assess real-world safety and treatment effectiveness of rFXIII-A2 prophylaxis from the mentor 6 trial.

Patients/methods: mentor 6 was a noninterventional, postauthorization safety study investigating rFXIII-A2 prophylaxis in FXIII-A CD. rFXIII-A2 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-A2. Of four MESIs, two were unlikely related to rFXIII-A2 (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-A2. 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-A2. Eight of nine minor surgeries performed during rFXIII-A2 prophylaxis reported successful hemostatic outcomes (one missing evaluation).

Conclusions: These data confirm that rFXIII-A2 prophylaxis is well tolerated as long-term care. There were no spontaneous bleeds, ABR was low, and rFXIII-A2 successfully treated bleeds in patients receiving rFXIII-A2 prophylaxis.

Keywords: factor XIII; long‐term care; recombinant factor XIII‐A2; safety; treatment effectiveness.

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Figures

FIGURE 1
FIGURE 1
Overall ABR summary from all mentor clinical trials. aNo spontaneous bleeds. bNo treatment‐requiring bleeds were reported. The planned Poisson analysis was not possible with a count of zero bleeds. Data are presented in a forest plot with estimated ABR and corresponding CI as whiskers, as derived in the respective clinical trial reports of mentor 1, mentor 2, mentor 5. Abbreviations: ABR, annualized bleeding rate; CI, confidence interval; NA, not available
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