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

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.

Clotting Factor Deficiencies as an Underlying Cause of Abnormal Uterine Bleeding in Women of Reproductive Age: A Literature Review

“…FXIIID concentrate is also the treatment of choice for women with FXIIID during gestation, although there is controversy regarding the dosage and intervals of administration [ 39 ]. Finally, recombinant factor XIII (rfXIII) has been proven to be a safe and efficacious treatment for patients with FXIIID and is gaining in popularity as a prophylaxis option [ 45 , 46 ].…”

Rare inherited coagulation disorders: no longer orphan and neglected

“…A wide range of medications is available to manage FXIII deficiency, including FFP, SD-FFP, cryoprecipitate, and a pdFXIII concentrate. However, recombinant FXIII (rFXIII-A2) is preferred when available in cases with FXIII A-subunit defects (95% of all deficient cases) owing to the small infusion volume, low risk of transfusion-associated adverse events, and more precise dosing [ 81 , 82 ]. Based on the MENTOR 2 study, a prospective multi-center observational study, a recommended prophylactic dosage of rFXIII every 4 weeks is 35 IU/kg [ 83 ].…”

The History of Factor XIII Deficiency

“…94 Several recent studies have since been performed and shown the safety of this product for prophylaxis and on-demand therapy. [95][96][97] The last and only curative therapeutic option for congenital FXIII deficiency is gene therapy. Although gene therapy has a long history in hemophilia A and B, it has not yet been used in rare bleeding disorders.…”