Literature search and detailed data on patient populations used to construct available FVIII population PK models
| Study . | Factor concentrate . | Endogenous FVIII, IU/mL . | Total population . | Pediatrics . | |||||
|---|---|---|---|---|---|---|---|---|---|
| N . | Age, y (range) . | BW, kg (range) . | Morphometric variables (range) . | N . | Age, y (range) . | BW, kg (range) . | |||
| Standard half-life factor concentrates | |||||||||
| Stass, 200617 | Kogenate-FS | <0.01-0.05 | 19 | Mean 13 (4-12) | Mean 56 (21-96) | LBW mean 44.8 (18-66) BSA mean 1.5 (21-96) | 19 | Mean 13 (4-12) | Mean 56 (21-96) |
| Bolon-Larger, 200739 | NA | <0.01-0.19 | 33 | 40 (7-77) | 68 (21-120) | BSA 1.76 (0.85-2.32) | NA | NA | NA |
| Bjorkman, 200919 | Several* | <0.01-0.05 | 34 | 24 (7-74) | 68 (26-124) | NA | 11 | 12 (7-17) | 44 (26-82) |
| Bjorkman, 201229 | Advate | ≤0.02 | 100 52 | 19 (10-66) 4 (1-6) | 68 (35-108) 16 (11-27) | NA NA | 45 52 | NA (1-6) 4 (1-6) | >35 16 (11-27) |
| Karafoulidou, 200942 | ReFacto | <0.01-0.17 | 28 | 34 (18-70) | 75 (54-104) | NA | — | — | — |
| Abrantes, 201711 | ReFacto, Xyntha | >0.01-0.40 | 754 | 23 (0-73) | 69 (3-134) | NA | 234 | NA (0-17)† | NA |
| Jiménez-Juste, 201543 | NovoEight | <0.01 | 76 | 21 (1-60) | 57‡ (12-107) | BMI 21.4 (12-34)§ | 30 | 6‡ (1-17) | 21 (12-66)‡ |
| Tiede, 202044 | NovoEight | <0.01 | 231 | 20 (1-60) | 63 (12-120) | BMI 23.7 (14-40)ǁ | 87 | 8 (1-17) | 27 (12-95) |
| Garmann, 201731 | Kovaltry | <0.01 | 183 | 22 (1-61) | 60 (11-124) | BMI 20.4 (13-38) LBW 54.1 (9-79) | >51¶ | 6 (1-11) | 23 (11-59) |
| Shah, 201745 | Kovaltry | <0.01 | 18 | 36 (19-64) | 80 (55-99) | BMI 26.1 (19-29) | — | — | — |
| McEneny-King, 201920 | All SHL | 0.05 | 310 | NA (1-62) | 660 (10-132) | NA | NA | NA | NA |
| Standard and extended factor concentrates | |||||||||
| Allard, 202018 | Several# | 0.01-mild | 258 | 30 (3-77) | 64 (15-130) | BMI 21.3 (13-45) | 87 | 10 (3-17)‡ | 37 (15-109)‡ |
| Extended half-life factor concentrates | |||||||||
| Zhang, 201746 | Afstyla** | <0.01 | 91 39 | 29 (12-60) 5 (1-11) | 72 (38-106) 23 (10-87) | BMI 23.7 (15-38) BMI 16.5 (13-30) | 10‡ 39 | 16 (12-17)‡ 5 (1-11) | 50 (37-100)‡ 23 (10-87) |
| Delavenne, 201847 | Nuwiq | <0.01 | 115 | 31 (2-67) | 70 (13-140) | NA | 29 | Otherwise† | NA |
| Nesterov, 201523 | Elocta | <0.01 | 180 | NA (12-65) | (42-127)‡‡ | NA | NAa | NA | NA |
| Bukkems, 202024 | Elocta | ≤0.02 | 43 | 28 (5-70) | 72 (20-113) | BMI 23.73 (13-34)‡ | 13‡ | 10 (5-17)‡ | 34 (20-113)‡ |
| Shah, 201921 | Jivi, Elocta | <0.01 | 18 | 34 (22-65) | NA | BMI 25.0 (19-30) | — | — | — |
| Solms, 202037 | Jivi | <0.01 | 198 | 29 (2-62) | 67 (12-126) | BMI 22.0 (13-42) LBW 49.0 (10-75) | 153 | NA (2-17)b | NA |
| Solms, 202022 | Jivi and Adynovi | <0.01 | 18 | 34 (23-56) | NA | BMI 24.45 (18-30) | — | — | — |
| Chelle, 202038 | Adynovi | <0.01 | 154 | 19 (3-72) | 70 (15-150) | BMI 23.2 (14-5) | NA | NAc | NA |
| Study . | Factor concentrate . | Endogenous FVIII, IU/mL . | Total population . | Pediatrics . | |||||
|---|---|---|---|---|---|---|---|---|---|
| N . | Age, y (range) . | BW, kg (range) . | Morphometric variables (range) . | N . | Age, y (range) . | BW, kg (range) . | |||
| Standard half-life factor concentrates | |||||||||
| Stass, 200617 | Kogenate-FS | <0.01-0.05 | 19 | Mean 13 (4-12) | Mean 56 (21-96) | LBW mean 44.8 (18-66) BSA mean 1.5 (21-96) | 19 | Mean 13 (4-12) | Mean 56 (21-96) |
| Bolon-Larger, 200739 | NA | <0.01-0.19 | 33 | 40 (7-77) | 68 (21-120) | BSA 1.76 (0.85-2.32) | NA | NA | NA |
| Bjorkman, 200919 | Several* | <0.01-0.05 | 34 | 24 (7-74) | 68 (26-124) | NA | 11 | 12 (7-17) | 44 (26-82) |
| Bjorkman, 201229 | Advate | ≤0.02 | 100 52 | 19 (10-66) 4 (1-6) | 68 (35-108) 16 (11-27) | NA NA | 45 52 | NA (1-6) 4 (1-6) | >35 16 (11-27) |
| Karafoulidou, 200942 | ReFacto | <0.01-0.17 | 28 | 34 (18-70) | 75 (54-104) | NA | — | — | — |
| Abrantes, 201711 | ReFacto, Xyntha | >0.01-0.40 | 754 | 23 (0-73) | 69 (3-134) | NA | 234 | NA (0-17)† | NA |
| Jiménez-Juste, 201543 | NovoEight | <0.01 | 76 | 21 (1-60) | 57‡ (12-107) | BMI 21.4 (12-34)§ | 30 | 6‡ (1-17) | 21 (12-66)‡ |
| Tiede, 202044 | NovoEight | <0.01 | 231 | 20 (1-60) | 63 (12-120) | BMI 23.7 (14-40)ǁ | 87 | 8 (1-17) | 27 (12-95) |
| Garmann, 201731 | Kovaltry | <0.01 | 183 | 22 (1-61) | 60 (11-124) | BMI 20.4 (13-38) LBW 54.1 (9-79) | >51¶ | 6 (1-11) | 23 (11-59) |
| Shah, 201745 | Kovaltry | <0.01 | 18 | 36 (19-64) | 80 (55-99) | BMI 26.1 (19-29) | — | — | — |
| McEneny-King, 201920 | All SHL | 0.05 | 310 | NA (1-62) | 660 (10-132) | NA | NA | NA | NA |
| Standard and extended factor concentrates | |||||||||
| Allard, 202018 | Several# | 0.01-mild | 258 | 30 (3-77) | 64 (15-130) | BMI 21.3 (13-45) | 87 | 10 (3-17)‡ | 37 (15-109)‡ |
| Extended half-life factor concentrates | |||||||||
| Zhang, 201746 | Afstyla** | <0.01 | 91 39 | 29 (12-60) 5 (1-11) | 72 (38-106) 23 (10-87) | BMI 23.7 (15-38) BMI 16.5 (13-30) | 10‡ 39 | 16 (12-17)‡ 5 (1-11) | 50 (37-100)‡ 23 (10-87) |
| Delavenne, 201847 | Nuwiq | <0.01 | 115 | 31 (2-67) | 70 (13-140) | NA | 29 | Otherwise† | NA |
| Nesterov, 201523 | Elocta | <0.01 | 180 | NA (12-65) | (42-127)‡‡ | NA | NAa | NA | NA |
| Bukkems, 202024 | Elocta | ≤0.02 | 43 | 28 (5-70) | 72 (20-113) | BMI 23.73 (13-34)‡ | 13‡ | 10 (5-17)‡ | 34 (20-113)‡ |
| Shah, 201921 | Jivi, Elocta | <0.01 | 18 | 34 (22-65) | NA | BMI 25.0 (19-30) | — | — | — |
| Solms, 202037 | Jivi | <0.01 | 198 | 29 (2-62) | 67 (12-126) | BMI 22.0 (13-42) LBW 49.0 (10-75) | 153 | NA (2-17)b | NA |
| Solms, 202022 | Jivi and Adynovi | <0.01 | 18 | 34 (23-56) | NA | BMI 24.45 (18-30) | — | — | — |
| Chelle, 202038 | Adynovi | <0.01 | 154 | 19 (3-72) | 70 (15-150) | BMI 23.2 (14-5) | NA | NAc | NA |
All data are reported in median (range) unless otherwise specified.
NA, not available.
Kogenate, Immunate, Helixate Nex Gen, Monoclate, Octanativ-MK.
Number of patients per age group: age 0-1 y, N = 62; age 1-2 y, N = 21; age 2-6 y, N = 8; age 6-12 y, N = 25; age 12-17 y, N =118.
Data provided by authors/pharmaceutical company on request.
BMI <18 y 16.2 (12.4-25.6), ≥18 y 23.5 (15.3-33.8).
BMI based on 168 patients (24 children <18 y and 144 adults).
Possibly 20 extra children from Leopold 1 and 2 study aged ≥12 y but not reported how many were included in final model.
Factane, Advate, Kogenate, Kovaltry, Afstyla, Refacto, NovoEight, Elocta.
PK model pooled from the 2 PK studies; data shown separately.
Number of patients per age group: age 2-5 y, N = 29; age 6-12 y, N = 30; age 12-18 y, N = 2.
Number of patients and median body weight per subgroup: subgroup 1, N = 16, median 82.7; subgroup 2, N = 164, median 71.6.
A maximum of 14 children aged ≥12 y until 18 y was included. No exact number available.
Therapeutic indicated and administered to patients ≥12 y. Number of patients per age group: age < 6 y, N = 32; age 6-12 y, N = 29; age >12 y, N = 13.
Therapeutic indicated and administered to patients ≥12 y.