Prophylactic treatment effects on inhibitor risk: experience in one centre

Morado, Marta; Villar, Ana; Jiménez‐Yuste, Víctor; Quintana, Manuel; Navarro, Felipe

doi:10.1111/j.1365-2516.2005.00921.x

Cited by 69 publications

(60 citation statements)

References 17 publications

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“…This clearly confirmed previous suggestions of a protective effect of prophylactic treatment. 18,22,32,33 Patient characteristics Furthermore, our study confirmed previous reports of an increased risk of inhibitor development in patients with a positive family history of inhibitors [5][6][7] and patients with large deletions, nonsense mutations, or intron 22 inversion in their factor VIII gene. 8,36,37 In addition, in agreement with previous observations, we did not find a relation between breastfeeding and inhibitor development.…”

Section: Regular Prophylaxissupporting

confidence: 87%

“…We had data on breastfeeding in 132 patients (36%). Ninety-one patients had been breastfed, for a median of 13 (IQR, [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] weeks. The inhibitor risk was similar in patients with and without breastfeeding.…”

Section: Missing Datamentioning

confidence: 99%

“…19,20 Intensive treatment was suggested to be a risk factor in patients with mild hemophilia A, who appeared to develop inhibitors more frequently after surgery. 21 A protective effect has been suggested for prophylactic treatment, 18,22 but additional studies are required to confirm this association. 23,24 Modifiable risk factors of inhibitors provide the key to predict and perhaps even prevent inhibitor development in hemophilia patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study

Gouw

Bom

Berg

2007

Blood

450

523

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Section: Regular Prophylaxissupporting

confidence: 87%

Section: Missing Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study

Gouw

Bom

Berg

2007

Blood

450

523

View full text Add to dashboard Cite

“…High-titer inhibitors developed in 66 patients and low-titer inhibitors, in 16 patients. Patients developed inhibitors after a median of 14 exposure days (interquartile range [IQR],[8][9][10][11][12][13][14][15][16][17][18][19] and at a median age of 15 months (IQR, 10-22 months). …”

mentioning

confidence: 99%

Recombinant versus plasma-derived factor VIII products and the development of inhibitors in previously untreated patients with severe hemophilia A: the CANAL cohort study

Gouw

Bom

Auerswald

et al. 2007

Blood

214

209

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It has been suggested that plasma-derived factor VIII products induce fewer inhibitors than recombinant factor VIII products. We investigated the relationship of factor VIII product type and switching between factor VIII products with the risk to develop inhibitors. This multicenter retrospective cohort study included 316 patients with severe hemophilia A born between 1990 and 2000. The outcome was clinically relevant inhibitor development, defined as the occurrence of at least 2 positive inhibitor titers with decreased recovery. The risk of inhibitor development was not clearly lower in plasma-derived compared with recombinant factor VIII products (relative risk [RR], 0.8; 95% confidence interval [CI], 0.5-1.3). Among high-titer inhibitors, the possible reduction in risk was even less pronounced (RR, 0.9; CI, 0.5-1.5). Plasma-derived products with considerable quantities of von Willebrand factor (VWF) carried the same risk for inhibitor development as recombinant factor VIII products (RR, 1.0; CI, 0.6-1.6). Switching between factor VIII products did not increase the risk for inhibitors (RR, 1.1; CI, 0.6-1.8). In conclusion, our findings support neither the notion that plasmaderived factor VIII products with considerable concentrations of VWF confer a lower risk to develop inhibitory antibodies than recombinant factor VIII products, nor that switching between factor VIII product brands increases inhibitor risks in previously untreated patients with severe hemophilia A. IntroductionAt present, the main concern in the treatment of children with severe hemophilia A is the development of inhibitory antibodies that neutralize infused factor VIII, occurring in 10% to 30% of patients. 1 Several patient-related factors have been associated with the risk of developing inhibitors, such as factor VIII gene mutation, 2-4 other genetic factors, 5-8 family history of inhibitors, 9-11 and ethnicity. 11,12 In addition to these determinants, a number of treatment-related factors have been suggested to affect the risk of inhibitor development, such as prophylaxis, 13,14 age at first exposure, 15,16 and intensity of treatment. 17 One of the most intensively discussed potential risk factors is the factor VIII product type.Indications for a potential role of the factor VIII product type in inhibitor development arose when prospective registration studies of recombinant factor VIII products among previously untreated hemophilia A patients reported inhibitor incidences between 29% and 32%. [18][19][20][21][22][23] These incidences were considerably higher than the previously observed 0% to 12% in patients treated with single plasma-derived products. 1,24 However, methodologic differences between studies rendered comparisons inconclusive. 25 More convincing were the findings of a recent comparative study in which the inhibitor risk in patients treated with full-length recombinant factor VIII was again higher than the risk in patients treated with a high-purity plasma-derived factor VIII product containing von Willebrand factor (VWF)...

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“…32 Much discussion has centred on whether the type of concentrate used, either plasma-derived or recombinant, has an impact on inhibitor development, and some researchers have Table 1). 51 ITI faces a number of potential obstacles in practice.…”

Section: Risk Factors For Inhibitor Developmentmentioning

confidence: 99%