Immune tolerance induction in haemophilia A patients with inhibitors by treatment with recombinant factor VIII: a retrospective non-interventional study

Haemophilia ◽  
2013 ◽  
Vol 19 (3) ◽  
pp. 449-455 ◽  
Author(s):  
G. E. Rivard ◽  
C. Rothschild ◽  
T. Toll ◽  
K. Achilles
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Interventional Study ◽  
Immune Tolerance Induction

scholarly journals Immune tolerance induction in haemophilia A patients with inhibitor using Fc fusion recombinant factor VIII product

2018 ◽  
Vol 29 (3) ◽  
pp. 307-314
Author(s):  
Azusa NAGAO ◽  
Kagehiro AMANO ◽  
Haruna KATAYAMA ◽  
Ryosuke HOSOKAI ◽  
Takeshi HAGIWARA ◽  
...  
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Recombinant Factor Viii ◽  
Haemophilia A ◽  
Immune Tolerance Induction ◽  
Viii Product

The long-term course of factor VIII inhibitors in patients with congenital haemophilia A without immune tolerance induction

2011 ◽  
Vol 105 (01) ◽  
pp. 59-65 ◽  
Author(s):  
Camila Caram ◽  
Roberta Grazielle de Souza ◽  
Júlio Carepa de Sousa ◽  
Tatiana Araújo Pereira ◽  
Ana Maria do Amaral Cerqueira ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Factor Viii ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Clotting Factor ◽  
Haemophilia A ◽  
Immune Tolerance Induction ◽  
Inhibitor Titre ◽  
Very High

SummaryThe development of alloantibodies that inhibit or neutralise the function of factor VIII is considered the most serious complication of the treatment of congenital haemophilia A. In order to describe their course without immune tolerance induction (ITI), we documented data on all performed inhibitor tests with dates as well as on clotting factor infusions of all consecutive patients who were treated in our centre between 1993 and 2006. Patients were tested every 7.1 months (95% confidence interval [CI], 6.6–7.8). A ‘sustained negative inhibitor status’ was defined as consistent non-positive inhibitor measurements for two years or longer. A total of 60/486 (12%) patients tested had a positive inhibitor titre in two or more occasions. Most of the patients (56%) with a maximum inhibitor titre of < 5 Bethesda unit (BU)/ml (named “low titre inhibitor”) developed a sustained negative inhibitor status. Among patients with high (5–9.9 BU/ml) and very high (≥ 10 BU/ ml) inhibitor titres, the proportions were 50% and 3%, respectively. Our findings suggest that ITI might not be needed for all patients with non-transient inhibitors, especially when their maximum inhibitor titre is below 10 BU/ml. Further studies in countries where ITI is not available are needed to examine predictors of the natural sustained negative inhibitor status.

Successful Treatment of Inhibitor Formation in Adult Congenital Hemophilia A with Rituximab.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4074-4074 ◽  
Author(s):  
Chirag J. Amin ◽  
Alice D. Ma
Keyword(s):  
Factor Viii ◽  
Knee Replacement ◽  
Immune Tolerance ◽  
Bolus Dose ◽  
Hemophilia A ◽  
High Titer ◽  
Tolerance Induction ◽  
Recombinant Factor Viii ◽  
Promising Alternative ◽  
Immune Tolerance Induction

Abstract Inhibitor development in congenital hemophiliacs can be clinically catastrophic. Immune tolerance induction therapy has previously been the standard of care in eradicating inhibitors; however due to a multitude of factors, this may not be applicable in certain patients. The role of Rituximab is receiving more attention in this subset of patients. In this abstract, we report that treatment with Rituximab led to successful eradication of high-titer inhibitors in 3 patients with mild to moderate hemophilia A who developed inhibitors after receiving intensive treatment with recombinant Factor VIII (FVIII). Patient Characteristics: Three patients, aged 50–70, with baseline FVIII levels of 2–9%, developed inhibitors after recombinant Factor VIII infusion. Patient A was treated with continuous infusion FVIII for a post-surgical hemarthrosis for approximately 7 days. Patient B received bolus dose FVIII for a GI bleed for at least 10 days, and Patient C received bolus dose FVIII for knee replacement for 10 days. Factor VIII inhibitors were detected in these patients after one month. None of these patients had been treated with immune tolerance previously or had known inhibitors. Each patient received Rituximab 375mg/m2 every week for 4 weeks total. During and after treatment, FVIII levels and Bethesda inhibitor titers (BU) were monitored. Results: All three patients had eradication of their inhibitors (Figure 1) and return of their FVIII levels to baseline by six months post-treatment. Notably, patient C’s inhibitor peak was 117 BUs, 7 months prior to Rituximab treatment. Patient C’s initial response to Rituximab has been previously reported at ASH in abstract form. We now report that 4 years later, this patient has had a recurrence of his inhibitor after monoclonal FVIII for a contralateral knee replacement but with a peak titer of only 2 (Table 1). Inhibitor Trends after Rituximab Treatment Inhibitor Trends after Rituximab Treatment Bethesda Inhibitor Titer (BU) per Month (*) after Receiving Rituximab 0* 1 3 6 36 48 51 NA=Not applicable as data has not matured yet Patient A (BU) 5 0.7 0 0 NA NA NA Patient B (BU) 17 7 2 0 NA NA NA Patient C (BU) 40 4 0 0 0 2 0.5 Conclusion: Inhibitors in patients with mild-moderate hemophilia differ from those with severe FVIII deficiency, behaving more like the autoantibodies seen in patients with spontaneous FVIII inhibitors. In support of this idea, we successfully treated high titer inhibitors which developed in 3 patients with baseline FVIII levels of 2–9%. All three patients had prompt resolution of their inhibitor titers during the course of therapy, with return of their baseline FVIII levels. Historically, patients with mild-moderate hemophilia treated at the Harold R. Roberts Comprehensive Hemophilia Center at the University of North Carolina were treated either with immune tolerance induction or by bypass agents alone, with inhibitor eradication taking months to years (data not shown). While performance of larger prospective trials would be ideal, the small number of patients with this condition limits the ability to perform these trials. Our findings, in combination with other case series from other institutions, reveal a promising alternative for prompt and reliable treatment in mild-moderate hemophiliacs with inhibitors.

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