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

Lone Hvitfeldt Poulsen; Bryce A Kerlin; Giancarlo Castaman; Angelo Claudio Molinari; Marzia Menegatti; Diane Nugent; Sohan Dey; May-Lill Garly; Manuel Carcao

doi:10.1002/rth2.12628

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

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

Authors

Lone Hvitfeldt Poulsen¹, Bryce A Kerlin², Giancarlo Castaman³, Angelo Claudio Molinari⁴, Marzia Menegatti⁵, Diane Nugent⁶, Sohan Dey⁷, May-Lill Garly⁸, Manuel Carcao⁹

Affiliations

¹ The Haemophilia Center Department of Hematology Aarhus University Hospital Aarhus Denmark.
² The Ohio State University College of Medicine Nationwide Children's Hospital Columbus Ohio USA.
³ Center for Bleeding Disorders and Coagulation Department of Oncology Careggi University Hospital Firenze Italy.
⁴ Regional Reference Center for Hemorrhagic Diseases Giannina Gaslini Children's Hospital Genoa Italy.
⁵ IRCCS Fondazione Ca' Granda Ospedale Maggiore Policlinico Angelo Bianchi Bonomi Hemophilia and Thrombosis Center Milan Italy.
⁶ Children's Hospital of Orange County University of California at Irvine, and Center for Inherited Blood Disorders Orange California USA.
⁷ Novo Nordisk Service Centre India Private Ltd Bangalore India.
⁸ Novo Nordisk A/S Søborg Denmark.
⁹ Division of Haematology/Oncology Department of Paediatrics and Child Health Evaluative Sciences Research Institute, Hospital for Sick Children University of Toronto Toronto Ontario Canada.

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.