Table 1

Patient characteristics according to the first factor VIII product received

Product E (Advate)Product D (Kogenate FS)Plasma-derived FVIII products
CharacteristicsN%ƠN%ƠN%
RODIN study1 * 157   183   88  
 High-risk F8 genotype 95 60.5 – 100 54.6 ++ 56 63.6 
 Family history of hemophilia and inhibitor 22 14.0 – 16 8.7 +++ 20 22.7 
 Nonwhite race 20 12.7 - 16 8.7 - 7 8.0 
 History of peak treatment episode on first exposure day ≥3 d 40 25.5 - 41 22.4 +++ 30 34.1 
 History of peak treatment episode on first exposure day ≥5 d 28 17.8 – 21 11.5 +++ 24 27.3 
UK Haemophilia Centre Doctors’ Organisation2 * 172   128     
 High-risk FVIII mutation (including inversion) 103 59.9 - 71 55.5    
 Family history of hemophilia and inhibitor 15 8.7 ++ 18 14.1    
 Nonwhite ethnicity 25 14.5 - 16 12.5    
 Intensive treatment (5 or more consecutive EDs‡) at first exposure 26 15.1 - 17 13.3    
FranceCoag Network3 * 97   111     
 High-risk F8 gene defect regardless of the date of genetic diagnosis 62 63.9 +++ 85 76.6    
 High-risk F8 gene defect known at first FVIII infusion§ 23 23.7 + 30 27.0    
 Family history of hemophilia and inhibitor regardless of date of appearance 9 9.3 + 15 13.5    
 Family history of hemophilia and inhibitor known at first FVIII infusion§ 6 6.2 - 6 5.4    
 Ethnic origin: Others (not white only) not African or African American 17 17.5 + 23 20.7    
 Ethnic origin: African or Afro-American (at least 1 grandparent) 6 6.2 - 3 2.7    
 Peak treatment episode at first exposure ≥3 consecutive EDs‡ 31 32.0 - 35 31.5    
 Peak treatment episode at first exposure ≥5 consecutive EDs 14 14.4 + 21 18.9    
 First exposure linked to surgical procedure (with ≥3 EDs) 2 2.1 - 1 0.9    
 First exposure linked to severe bleeding episode 10 10.3 - 10 9.0    
 At least 2 of the above-mentioned factors known at first FVIII infusion‖ 27 27.8 - 30 27.0    
 At least 3 of the above-mentioned factors known at first FVIII infusion‖ 6 6.2 + 10 9.0    
FranceCoag Network: 3 selected HTCs (Lille, Necker, and Strasbourg)§ 18   47     
 High-risk F8 gene defect known at first FVIII infusion 4 22.2 + 11 23.4    
 Family history of hemophilia and inhibitor known at first FVIII infusion 3 16.7 — 3 6.4    
 Ethnic origin: Others (not white only) not African or African American 6 33.3 - 14 29.8    
 Ethnic origin: African or Afro-American (at least one grandparent) 3 16.7 — 0 0.0    
 Peak treatment episode at first exposure ≥3 consecutive EDs‡ 8 44.4 — 13 27.7    
 Peak treatment episode at first exposure ≥5 consecutive EDs 2 11.1 ++ 10 21.3    
 First exposure linked to surgical procedure (with ≥3 EDs) 0 0.0 + 1 2.1    
 First exposure linked to severe bleeding episode 1 5.6 - 2 4.3    
 At least 2 of the above-mentioned factors‖ 8 44.4 — 10 21.3    
 At least 3 of the above-mentioned factors‖ 2 11.1 + 6 12.8    
FranceCoag Network: 30 remaining HTCs§ 79   64     
 High-risk F8 gene defect known at first FVIII infusion 19 24.1 ++ 19 29.7    
 Family history of hemophilia and inhibitor known at first FVIII infusion 3 3.8 + 3 4.7    
 Ethnic origin: Others (not white only) not African or African American 11 13.9 + 9 14.1    
 Ethnic origin: African or Afro-American (at least 1 grandparent) 3 3.8 + 3 4.7    
 Peak treatment episode at first exposure ≥3 consecutive EDs‡ 23 29.1 + 22 34.4    
 Peak treatment episode at first exposure ≥5 consecutive EDs 12 15.2 + 11 17.2    
 First exposure linked to surgical procedure (with ≥3 EDs) 2 2.5 - 0 0.0    
 First exposure linked to severe bleeding episode 9 11.4 + 8 12.5    
 At least 2 of the above-mentioned factors‖ 19 24.1 ++ 20 31.3    
 At least 3 of the above-mentioned factors‖ 4 5.1 + 4 6.3    
Product E (Advate)Product D (Kogenate FS)Plasma-derived FVIII products
CharacteristicsN%ƠN%ƠN%
RODIN study1 * 157   183   88  
 High-risk F8 genotype 95 60.5 – 100 54.6 ++ 56 63.6 
 Family history of hemophilia and inhibitor 22 14.0 – 16 8.7 +++ 20 22.7 
 Nonwhite race 20 12.7 - 16 8.7 - 7 8.0 
 History of peak treatment episode on first exposure day ≥3 d 40 25.5 - 41 22.4 +++ 30 34.1 
 History of peak treatment episode on first exposure day ≥5 d 28 17.8 – 21 11.5 +++ 24 27.3 
UK Haemophilia Centre Doctors’ Organisation2 * 172   128     
 High-risk FVIII mutation (including inversion) 103 59.9 - 71 55.5    
 Family history of hemophilia and inhibitor 15 8.7 ++ 18 14.1    
 Nonwhite ethnicity 25 14.5 - 16 12.5    
 Intensive treatment (5 or more consecutive EDs‡) at first exposure 26 15.1 - 17 13.3    
FranceCoag Network3 * 97   111     
 High-risk F8 gene defect regardless of the date of genetic diagnosis 62 63.9 +++ 85 76.6    
 High-risk F8 gene defect known at first FVIII infusion§ 23 23.7 + 30 27.0    
 Family history of hemophilia and inhibitor regardless of date of appearance 9 9.3 + 15 13.5    
 Family history of hemophilia and inhibitor known at first FVIII infusion§ 6 6.2 - 6 5.4    
 Ethnic origin: Others (not white only) not African or African American 17 17.5 + 23 20.7    
 Ethnic origin: African or Afro-American (at least 1 grandparent) 6 6.2 - 3 2.7    
 Peak treatment episode at first exposure ≥3 consecutive EDs‡ 31 32.0 - 35 31.5    
 Peak treatment episode at first exposure ≥5 consecutive EDs 14 14.4 + 21 18.9    
 First exposure linked to surgical procedure (with ≥3 EDs) 2 2.1 - 1 0.9    
 First exposure linked to severe bleeding episode 10 10.3 - 10 9.0    
 At least 2 of the above-mentioned factors known at first FVIII infusion‖ 27 27.8 - 30 27.0    
 At least 3 of the above-mentioned factors known at first FVIII infusion‖ 6 6.2 + 10 9.0    
FranceCoag Network: 3 selected HTCs (Lille, Necker, and Strasbourg)§ 18   47     
 High-risk F8 gene defect known at first FVIII infusion 4 22.2 + 11 23.4    
 Family history of hemophilia and inhibitor known at first FVIII infusion 3 16.7 — 3 6.4    
 Ethnic origin: Others (not white only) not African or African American 6 33.3 - 14 29.8    
 Ethnic origin: African or Afro-American (at least one grandparent) 3 16.7 — 0 0.0    
 Peak treatment episode at first exposure ≥3 consecutive EDs‡ 8 44.4 — 13 27.7    
 Peak treatment episode at first exposure ≥5 consecutive EDs 2 11.1 ++ 10 21.3    
 First exposure linked to surgical procedure (with ≥3 EDs) 0 0.0 + 1 2.1    
 First exposure linked to severe bleeding episode 1 5.6 - 2 4.3    
 At least 2 of the above-mentioned factors‖ 8 44.4 — 10 21.3    
 At least 3 of the above-mentioned factors‖ 2 11.1 + 6 12.8    
FranceCoag Network: 30 remaining HTCs§ 79   64     
 High-risk F8 gene defect known at first FVIII infusion 19 24.1 ++ 19 29.7    
 Family history of hemophilia and inhibitor known at first FVIII infusion 3 3.8 + 3 4.7    
 Ethnic origin: Others (not white only) not African or African American 11 13.9 + 9 14.1    
 Ethnic origin: African or Afro-American (at least 1 grandparent) 3 3.8 + 3 4.7    
 Peak treatment episode at first exposure ≥3 consecutive EDs‡ 23 29.1 + 22 34.4    
 Peak treatment episode at first exposure ≥5 consecutive EDs 12 15.2 + 11 17.2    
 First exposure linked to surgical procedure (with ≥3 EDs) 2 2.5 - 0 0.0    
 First exposure linked to severe bleeding episode 9 11.4 + 8 12.5    
 At least 2 of the above-mentioned factors‖ 19 24.1 ++ 20 31.3    
 At least 3 of the above-mentioned factors‖ 4 5.1 + 4 6.3    
*

The risk factor designations used in the original articles have been kept.

†

∆ is the difference between risk factor prevalences of adjacent columns: in support of confounding by indication (CbI) [+ (∆>0), ++ (∆>5), +++ (∆>10)] or not in support of CbI [- (∆<0), – (∆<–5), — (∆<−10)].

‡

An exposure day (ED) was defined as a day during which one or more infusions of FVIII were given.

§

Results not shown in the original article.

‖The factor “Peak treatment episode at first exposure ≥5 consecutive EDs” was not considered in this definition because it is redundant with the factor “Peak treatment episode at first exposure ≥3 consecutive EDs.”

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