A matching‐adjusted indirect comparison in patients with severe haemophilia A: Comparing the efficacy and consumption of rVIII-SingleChain vs two recombinant FVIII

SummaryInhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study’s objective to assess inhibitor development according to clotting factor concentrate in severe haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was set up as a study monitoring adverse events overall and according to concentrate. Since October 2008, inhibitors were reported at least quarterly. Number of treated patients was reported annually, specifying the number of patients completing 50 exposure days (Previously Untreated Patients, PUPs) without inhibitor development. Cumulative incidence, incidence rates and 95 % confidence intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012 were analysed for 68 centres that validated their data. Inhibitors developed in 108/417 (26 %; CI 22–30 %) PUPs with severe haemophilia A and 5/72 (7 %; CI 2–16%) PUPs with severe haemophilia B. For Previously Treated Patients (PTPs), 26 inhibitors developed in 17,667 treatment years [0.15/100 treatment years; CI 0.10–0.22) for severe haemophilia A and 1/2836 (0.04/100; (CI 0.00–0.20) for severe haemophilia B. Differences between plasma-derived and recombinant concentrates, or among the different recombinant FVIII concentrates were investigated. In conclusion, while confirming the expected rates of inhibitors in PUPs and PTPs, no class or brand related differences were observed.

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Absence of Inhibitors in Previously Untreated Patients with Severe Haemophilia A after Exposure to a Single Intermediate Purity Factor VIII Product

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657681 ◽

1997 ◽

Vol 78 (03) ◽

pp. 1027-1029 ◽

Cited By ~ 48

Author(s):

T T Yee ◽

M D Williams ◽

F G H Hill ◽

C A Lee ◽

K J Pasi

Keyword(s):

Factor Viii ◽

High Purity ◽

Specific Activity ◽

Haemophilia A ◽

Severe Haemophilia ◽

True Incidence ◽

Conventional Fractionation ◽

Heat Treated ◽

Recombinant Fviii ◽

Von Willebrand

SummaryUse of high purity and recombinant factor VIII (FVIII) concentrates has been thought to be associated with an increased incidence of FVIII inhibitors in patients with severe haemophilia A. Comparison with comparable historical control groups has suggested that the true incidence of inhibitors in patients with severe haemophilia A was ~20-25%, similar to the incidence seen with new high purity and recombinant FVIII products.We have conducted a study of inhibitor development in a cohort of 37 boys with severe haemophilia A (VIII: C <2 u/dl) exposed only to a single FVIII concentrate (BPL 8Y) with no previous blood or blood product exposure. This factor VIII concentrate is an intermediate purity product with a specific activity of ~2 IU/mg protein and contains well preserved von Willebrand factor multimers. It is manufactured by conventional fractionation technologies and terminally dry heat treated at 80° C for 72 h.

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Case Report on a Female Patient with Congenital Haemophilia a and An Acquired Type-2 Inhibitor to FVIII

Blood ◽

10.1182/blood.v112.11.4525.4525 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4525-4525

Author(s):

Karin Kurnik ◽

Christoph Bidlingmaier

Keyword(s):

Half Life ◽

Female Child ◽

Haemophilia A ◽

Severe Haemophilia ◽

Hormonal Change ◽

Fviii Inhibitor ◽

Intron 22 Inversion ◽

Depth Analysis ◽

Recombinant Fviii

Abstract Only rare cases of female haemophilia have been reported. Moreover, no case of congenital haemophilia A associated with an acquired type-2 inhibitor to FVIII in a female child has been described in literature yet. We report the case of a 15-year old girl, diagnosed with severe haemophilia A (FVIII:C <1%) at the age of 13 months. Her father suffered from severe haemophilia A (FVIII:C <1%) due to an intron 22 inversion. In the girl both an intron 22 inversion and a non-random X-inactivation were found. At 3 years the girl received prophylactic treatment, and recombinant FVIII (3 × 40 IU/kg/week) from 6 years of age. Bleeding episodes were rare. Aged 13 she developed two large spontaneous haematomas. In-depth analysis confirmed decreased FVIII-recovery, –half-life and an inhibitor titre of 7.6 BU following type-2 kinetics (haemophilic autoantibodies). All of the few reported children with an aquired FVIII inhibitor presented with other autoimmune diseases or had used penicillin. Our patient showed none of this, but interestingly experienced menarche 4 weeks after inhibitor detection. This lets us speculate that the ethiology of the inhibitor formation in our patient at the time of hormonal change might be similar to that in pregnant or postpartum women. Taking into account the recommendations of Ma et al. (2006) regarding inhibitor development during pregnancy in healthy women, we initiated a modified ITI with 75 IU/kg rFVIII concentrate (4,000 IU per infusion) every other day without additional immunosuppressive therapy. After 6 weeks of ITI, inhibitor titres declined and became negative after 8 months, resulting in a normal FVIII half-life till now.

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