scholarly journals Real‐world data of immune tolerance induction using recombinant factor VIII Fc fusion protein in patients with severe haemophilia A with inhibitors at high risk for immune tolerance induction failure: A follow‐up retrospective analysis

Haemophilia ◽  
2020 ◽  
Author(s):  
Manuel Carcao ◽  
Amy Shapiro ◽  
Nina Hwang ◽  
Steven Pipe ◽  
Sanjay Ahuja ◽  
...  
Keyword(s):  
High Risk ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Real World Data ◽  
Immune Tolerance Induction ◽  
Fc Fusion Protein ◽  
Induction Failure

scholarly journals Recombinant factor VIII Fc fusion protein for immune tolerance induction in patients with severe haemophilia A with inhibitors-A retrospective analysis

Haemophilia ◽  
2018 ◽  
Vol 24 (2) ◽  
pp. 245-252 ◽  
Author(s):  
M. Carcao ◽  
A. Shapiro ◽  
J. M. Staber ◽  
N. Hwang ◽  
C. Druzgal ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Factor Viii ◽  
Retrospective Analysis ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Immune Tolerance Induction ◽  
Fc Fusion Protein

First-line immune tolerance induction for children with severe haemophilia A: A protocol from the UK Haemophilia Centre Doctors' Organisation Inhibitor and Paediatric Working Parties

Haemophilia ◽  
2017 ◽  
Vol 23 (5) ◽  
pp. 654-659 ◽  
Author(s):  
P. Collins ◽  
E. Chalmers ◽  
J. Alamelu ◽  
C. Hay ◽  
R. Liesner ◽  
...  
Keyword(s):  
Immune Tolerance ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
First Line ◽  
Immune Tolerance Induction ◽  
The Uk

scholarly journals Immune Tolerance Induction with Simoctocog Alfa (Nuwiq®) in Six Patients with Severe Haemophilia a and FVIII Inhibitors

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5037-5037
Author(s):  
Neha Bhatnagar ◽  
Kate Khair ◽  
Ri Liesner ◽  
Alice Wilkinson ◽  
Larisa Belyanskaya
Keyword(s):  
Immune Tolerance ◽  
Half Life ◽  
Research Funding ◽  
Poor Prognosis ◽  
Case Series ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Immune Tolerance Induction ◽  
Inhibitor Titre

Abstract Introduction and Objective: Inhibitors to coagulation factor VIII (FVIII) are the most serious complication of haemophilia A treatment. Previously untreated patients (PUPs) are at the greatest risk of inhibitors, which generally occur within the first 20 exposure days (ED) to FVIII. Immune tolerance induction (ITI) is the only clinically proven strategy for eradication of inhibitors. We present a case series of six PUPs with severe haemophilia A and inhibitors who underwent ITI with simoctocog alfa (Nuwiq®), a 4th generation human cell-line-derived recombinant FVIII approved for treatment of haemophilia A. Materials and Methods: Six male PUPs with severe haemophilia A who developed FVIII inhibitors after treatment with simoctocog alfa were started on ITI with simoctocog alfa. Primarily, we assessed the success of simoctocog alfa in patients with inhibitors. Success of ITI was determined based on undetectable inhibitor titre (< 0.6 BU/ml), FVIII recovery ≥ 66% and half-life ≥ 6 hours. Secondary objectives were to assess bleeding rate, tolerability and safety in patients with inhibitors treated with simoctocog alfa ITI. Results: The age of the patients at the start of ITI ranged from 8 to 186 months. Four of the patients were Caucasian, and two were African. All patients had a F8 mutation associated with high risk of ITI failure and two patients had an additional risk factor for ITI failure. The number of EDs prior to inhibitor development ranged from 9 to 33, and the peak inhibitor titre ranged from 0.9 to 114 BU. For ITI, five patients were treated with 100 IU/kg simoctocog alfa daily, and one with 90 IU/kg every other day. One patient achieved complete tolerisation and is now on prophylaxis at normal doses, having achieved an undetectable inhibitor titre after 9 months. This was despite an inhibitor titre ≥ 10 BU/mL at ITI start, which is considered a poor prognosis factor for ITI success. Three other patients achieved an undetectable inhibitor titre after 1, 6 and 18 months of ITI, and FVIII recovery has normalised but half-life remains short and they are on weaning doses as the half-life extends. One patient discontinued ITI with simoctocog alfa after 15 months due to an increasing inhibitor level. This patient was 15 years old at ITI start, and older age is associated with poor ITI outcome. Additionally, his haemophilia A was untreated for 15 years, during which time he developed severe arthropathy. One patient, who started ITI 3 months ago, has an ongoing inhibitor titre and continues on ITI with simoctocog alfa. Conclusions: In a case series of six patients treated with simoctocog alfa for ITI, who all had poor prognosis factors for ITI success, four patients (67%) to date have achieved an undetectable inhibitor titre. These data suggest that ITI with simoctocog alfa may be an effective treatment approach in haemophilia A patients with inhibitors. Disclosures Khair: Shire, SOBI, Pfizer, Roche, Novo Nordisk, Octapharma: Speakers Bureau; shire, SOBI, Pfizer, Roche: Research Funding. Liesner:Roche: Research Funding; Novo Nordisk: Research Funding, Speakers Bureau; Baxalta: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Octapharma: Consultancy, Other: Clinical study investigator for NuProtect Study (Octapharma sponsored), Research Funding, Speakers Bureau; Sobi: Speakers Bureau. Belyanskaya:Octapharma AG: Employment.

Use of Haemate®P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: a multicentre observational study

Haemophilia ◽  
2012 ◽  
Vol 19 (2) ◽  
pp. 281-286 ◽  
Author(s):  
C. Rothschild ◽  
R. D'oiron ◽  
A. Borel-derlon ◽  
Y. Gruel ◽  
R. Navarro ◽  
...  
Keyword(s):  
Observational Study ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Immune Tolerance Induction

Immune tolerance induction using Fc‐fusion‐protein recombinant factor IX in severe haemophilia B

Haemophilia ◽  
2021 ◽  
Author(s):  
Ali Amid ◽  
Heather Perkins ◽  
Julie Gauthier ◽  
Arnaud Bonnefoy ◽  
Manuel Carcao ◽  
...  
Keyword(s):  
Fusion Protein ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Factor Ix ◽  
Severe Haemophilia ◽  
Immune Tolerance Induction ◽  
Haemophilia B ◽  
Fc Fusion Protein ◽  
Recombinant Factor Ix

Successful low dose immune tolerance induction in severe haemophilia A with inhibitors below 40 Bethesda Units

Haemophilia ◽  
2009 ◽  
Vol 16 (102) ◽  
pp. 71-79 ◽  
Author(s):  
P. C. TER AVEST ◽  
K. FISCHER ◽  
S. C. GOUW ◽  
K. VAN DIJK ◽  
E. P. MAUSER-BUNSCHOTEN
Keyword(s):  
Immune Tolerance ◽  
Low Dose ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Immune Tolerance Induction

Immuntoleranzinduktion mit hoch dosiertem FVIII und intravenösen Immunglobulin-Pulsen

2010 ◽  
Vol 30 (S 01) ◽  
pp. S119-S121 ◽  
Author(s):  
C. Pinkwart ◽  
R. Haase ◽  
N. Merkel ◽  
D. Forsberg ◽  
C. Mauz-Körholz ◽  
...  
Keyword(s):  
Body Weight ◽  
Immune Tolerance ◽  
Half Life ◽  
Tolerance Induction ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Initial Exposure ◽  
Immune Tolerance Induction ◽  
Fviii Inhibitor ◽  
Inhibitor Level

SummaryThe development of neutralizing allo-antibodies against factor VIII (FVIII) or FVIII inhibitors is a severe complication in the treatment of haemophilia A. About 25% of the children with severe haemophilia A develop FVIII inhibitors. Here we report on a boy with severe haemophilia A and intron 22 inversion of the FVIII gene who was diagnosed at ten months of age. After 16 exposure days to FVIII (81 days after initial exposure) he developed a FVIII inhibitor (maximum: 9.76 BU/ml). Therapy: We started immune tolerance induction (ITI) according to the Bonn protocol with high dose plasma derived FVIII concentrate (100 IU per kg body weight) twice daily. For additional inhibitor elimination treatment the patient received intravenous immunoglobulin (ivIg) at a dose of 1–2 g/kg body weight every 4 to 6 weeks. After start of treatment a rapid decline of the inhibitor level was observed, nevertheless low FVIII inhibitor levels persisted (<5 BU/ ml). Furthermore, the FVIII half-life was still accelerated. However, after every course of ivIg the inhibitor level declined and FVIII half-life was prolonged. Currently, the FVIII half-life is approaching normal values after more than seven months of ITI duration. Conclusion: Additional application of immunoglobulin is beneficial for immune tolerance induction.

Risk Factors for the Progression from Low to High Titres in 260 Children with Severe Haemophilia A and Newly Developed Inhibitors

2017 ◽  
Vol 117 (12) ◽  
pp. 2274-2282 ◽  
Author(s):  
Maria Elisa Mancuso ◽  
Kathelijn Fischer ◽  
Elena Santagostino ◽  
Johannes Oldenburg ◽  
Helen Platokouki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Immune Tolerance ◽  
Laboratory Data ◽  
Tolerance Induction ◽  
High Titre ◽  
High Dose ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Immune Tolerance Induction ◽  
Potential Risk Factors

AbstractIn children with severe haemophilia A, inhibitors to factor VIII (FVIII) usually develop during the first 50 treatment exposure days and are classified as low or high titre depending on the peak inhibitor titre being greater or less than 5 Bethesda units/mL (BU/mL). Classification of the inhibitor may change with time, as some low-titre inhibitors progress to high titre following re-exposure to FVIII concentrate. The aim of this study was to investigate potential risk factors for such a progression in children with severe haemophilia A and newly diagnosed inhibitors. This study was a follow-up study of the PedNet Registry and included 260 children with severe haemophilia A and inhibitors born between 1990 and 2009 and recruited consecutively from 31 haemophilia centres. Clinical and laboratory data were collected from the date of each child's first positive inhibitor test for at least 3 years. At the time of first positive inhibitor test, 49% (n = 127) had low-titre inhibitors, with 50% of them progressing to high titre and only 25% maintaining low titres. The FVIII gene (F8) mutation type was known in 247 patients (95%), and included 202 (82%) null mutations. The progression to high-titre inhibitors was associated with null F8 mutations (odds ratio [OR]: 2.6; 95% confidence interval [CI]: 1.0–6.5), family history of inhibitors (OR: 7.2; 95% CI: 1.8–28.4) and the use of high-dose immune tolerance induction, defined as ≥100 IU FVIII concentrate/kg/d (OR: 3.9; 95% CI: 1.5–10.0). These results suggest that high-dose immune tolerance induction should be avoided as the initial strategy in patients who develop low-titre FVIII inhibitors.

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