Efficacy and safety of prophylactic treatment with plasma‐derived factor XIII concentrate (human) in patients with congenital factor XIII deficiency

Abstract

Summary. Congenital factor XIII (FXIII) deficiency is an extremely rare, potentially life-threatening bleeding disorder. Routine prophylactic management is recommended for individuals with clinically relevant FXIII deficiency. This prospective, multicentre, openlabel study evaluated the long-term efficacy and safety of prophylactic infusions of FXIII concentrate (human) 40 IU kg À1 in patients with congenital FXIII deficiency. FXIII concentrate (human) was administered every 4 weeks for 12 months. Dosing was adjusted to maintain trough FXIII activity levels of 5-20%. Logistical and ethical constraints precluded use of a placebo control group. Annualized incidence of spontaneous bleeding was compared with historical rates; safety was assessed as a secondary objective. Forty-one patients were enrolled and completed the study. The annualized rate for spontaneous bleeding episodes requiring FXIII treatment was 0.000 episodes per patient-year (95% CI: 0.000; 0.097). The study met its primary endpoint: the upper limit of the 95% CI was substantially below the historical rate of 2.5 bleeding episodes per patient-year. Five spontaneous bleeding episodes (involving three patients; none requiring FXIII treatment) and eight trauma-related bleeding episodes (two requiring FXIII treatment) occurred. Five patients had surgery during the study, only one of whom required FXIII treatment for post-surgical bleeding. Most patients (≥85%) had trough FXIII activity levels ≥10%. No patient discontinued treatment due to an adverse event. No adverse events related to thromboembolism or viral transmission were reported. Prophylactic treatment with FXIII concentrate (human) was well tolerated and prevented spontaneous bleeding episodes that were serious enough to require treatment with FXIII-containing product. Clinical trial registration: www.clinicaltrials.gov/ct2/show/NCT00885742.

Safety of Factor XIII Concentrate: Analysis of More than 20 Years of Pharmacovigilance Data

“…In the preliminary report, the total number of AEs was not reported; however, possible treatment-related AEs were reported in 3 subjects [10]. The full data was published in 2015, and clarified the possible treatment-related AEs as knee pain and swelling, finger and elbow swelling, pruritis in both hands and redness, and an increase in TAT complex [28]. In addition, 4 subjects experienced 5 serious AEs (hip injury, traumatic chest injury, severe appendicitis, severe urinary tract infection, and chest pain) which were judged unrelated or unlikely to be related to study medication [10].…”

Tailored prophylaxis with rFXIII (NovoThirteen®) in a young girl with severe FXIII deficiency and previous cephalohaematoma

“…Therefore, the FXIII activity assay should be performed as soon as FXIII deficiency is suspected. 5 In the past, prophylaxis consisted of fresh frozen plasma (FFP) or cryoprecipitate, long before plasma-derived FXIII concentrates were licensed. The FXIII plasma levels are often not quantifiable in patients with severe FXIII deficiency (homozygous), whereas they are about 50%-70% of normal in those with a heterozygous defect.…”

“…5,6 In early 2016, a novel recombinant FXIII (rFXIII) concentrate (Catridecacog; NovoThirteen ® , Novo Nordisk HealthCare AG, Switzerland) was licensed with a recommended dosage of 35 IU/kg every 4 weeks. 5,6 In early 2016, a novel recombinant FXIII (rFXIII) concentrate (Catridecacog; NovoThirteen ® , Novo Nordisk HealthCare AG, Switzerland) was licensed with a recommended dosage of 35 IU/kg every 4 weeks.…”

Minimal factor XIII activity level to prevent major spontaneous bleeds

“…Retrospective analyses, clinical trials and, more recently, prospective analyses have shown that prophylactic treatment with FXIII concentrate can produce sufficient FXIII activity levels for normal hemostasis [21][22][23][24].…”