Inhibitor risk of the 19 F8 mutations in which inhibitor development occurred
| F8 mutation . | No. of patients n (%)* . | No. of patients with inhibitor n (%) . | Baseline FVIII:C, IU/dL median (min-max) . | End of follow-up† (Cum no. ED) . | No. of patients under observation at 20 ED . | Inhibitor risk at 20 ED‡ % (95%CI) . | No. of patients under observation at 50 ED . | Inhibitor risk at 50 ED‡ % (95% CI) . |
|---|---|---|---|---|---|---|---|---|
| Mutations in 10 or more patients | ||||||||
| Arg531Cys | 35 (3.2) | 1 (2.9) | 8 (2-37) | >100 | 25 | 0.0 | 16 | 0.0§ |
| Arg593Cys|| | 106 (9.5) | 12 (11.3) | 17 (5-32) | >100 | 35 | 9.1 (2-16) | 16 | 18.3 (7-30) |
| Asn618Ser | 58 (5.2) | 1 (1.7) | 24 (8-37) | >100 | 18 | 2.9 (0-9) | 5 | 2.9 (0-9) |
| Asp2074Gly | 11 (1.0) | 3 (27.3) | 8 (4-14) | >100 | 7 | 21.2 (0-47) | 5 | 21.2 (0-47) |
| Arg2150His | 57 (5.1) | 9 (15.8) | 7 (2-32) | >100 | 36 | 2.2 (0-7) | 20 | 12.2 (1-24) |
| Arg2159Cys | 21 (1.9) | 3 (14.3) | 14 (6-29) | >100 | 8 | 9.1 (0-26) | 3 | 39.4 (3-75) |
| Trp2229Cys | 10 (0.9) | 5 (50.0) | 8 (5-24) | 50-100 | 4 | 41.7 (5-78) | 3 | 41.7 (5-78) |
| Mutations in less than 10 patients | ||||||||
| Leu412Phe | 5 (0.4) | 1 (20.0) | 8 (3-14) | >100 | ||||
| Pro1761Gln | 2 (0.2) | 1 (50.0) | 6 (5-6) | >100 | ||||
| Phe1775Val | 3 (0.3) | 2 (66.7) | 27 (13-29) | 10-20 | ||||
| Arg1781Gly | 4 (0.4) | 1 (25.0) | 8 (6-16) | 50-100 | ||||
| Pro1854Leu | 4 (0.4) | 1 (25.0) | 14 (6-25) | >100 | ||||
| Arg1997Trp | 3 (0.3) | 2 (66.7) | 4 (4-6) | >100 | ||||
| Phe2101Cys | 2 (0.2) | 2 (100) | 7 (6-7) | 50-100 | ||||
| Tyr2105Cys | 6 (0.5) | 3 (50.0) | 19 (12-28) | 20-30 | ||||
| Glu2228Asp | 3 (0.3) | 1 (33.3) | 27 (16-36) | 10-20 | ||||
| Val2232Ala | 1 (0.1) | 1 (100.0) | 15 | 30-50 | ||||
| His2309Asp | 1 (0.1) | 1 (100.0) | 2 | 30-50 | ||||
| Stop2333Cys | 1 (0.1) | 1 (100.0) | 11 | 5-10 | ||||
| Total | 333 (29.9) | 51 (15.3) | ||||||
| F8 mutation . | No. of patients n (%)* . | No. of patients with inhibitor n (%) . | Baseline FVIII:C, IU/dL median (min-max) . | End of follow-up† (Cum no. ED) . | No. of patients under observation at 20 ED . | Inhibitor risk at 20 ED‡ % (95%CI) . | No. of patients under observation at 50 ED . | Inhibitor risk at 50 ED‡ % (95% CI) . |
|---|---|---|---|---|---|---|---|---|
| Mutations in 10 or more patients | ||||||||
| Arg531Cys | 35 (3.2) | 1 (2.9) | 8 (2-37) | >100 | 25 | 0.0 | 16 | 0.0§ |
| Arg593Cys|| | 106 (9.5) | 12 (11.3) | 17 (5-32) | >100 | 35 | 9.1 (2-16) | 16 | 18.3 (7-30) |
| Asn618Ser | 58 (5.2) | 1 (1.7) | 24 (8-37) | >100 | 18 | 2.9 (0-9) | 5 | 2.9 (0-9) |
| Asp2074Gly | 11 (1.0) | 3 (27.3) | 8 (4-14) | >100 | 7 | 21.2 (0-47) | 5 | 21.2 (0-47) |
| Arg2150His | 57 (5.1) | 9 (15.8) | 7 (2-32) | >100 | 36 | 2.2 (0-7) | 20 | 12.2 (1-24) |
| Arg2159Cys | 21 (1.9) | 3 (14.3) | 14 (6-29) | >100 | 8 | 9.1 (0-26) | 3 | 39.4 (3-75) |
| Trp2229Cys | 10 (0.9) | 5 (50.0) | 8 (5-24) | 50-100 | 4 | 41.7 (5-78) | 3 | 41.7 (5-78) |
| Mutations in less than 10 patients | ||||||||
| Leu412Phe | 5 (0.4) | 1 (20.0) | 8 (3-14) | >100 | ||||
| Pro1761Gln | 2 (0.2) | 1 (50.0) | 6 (5-6) | >100 | ||||
| Phe1775Val | 3 (0.3) | 2 (66.7) | 27 (13-29) | 10-20 | ||||
| Arg1781Gly | 4 (0.4) | 1 (25.0) | 8 (6-16) | 50-100 | ||||
| Pro1854Leu | 4 (0.4) | 1 (25.0) | 14 (6-25) | >100 | ||||
| Arg1997Trp | 3 (0.3) | 2 (66.7) | 4 (4-6) | >100 | ||||
| Phe2101Cys | 2 (0.2) | 2 (100) | 7 (6-7) | 50-100 | ||||
| Tyr2105Cys | 6 (0.5) | 3 (50.0) | 19 (12-28) | 20-30 | ||||
| Glu2228Asp | 3 (0.3) | 1 (33.3) | 27 (16-36) | 10-20 | ||||
| Val2232Ala | 1 (0.1) | 1 (100.0) | 15 | 30-50 | ||||
| His2309Asp | 1 (0.1) | 1 (100.0) | 2 | 30-50 | ||||
| Stop2333Cys | 1 (0.1) | 1 (100.0) | 11 | 5-10 | ||||
| Total | 333 (29.9) | 51 (15.3) | ||||||
Percentage of total cohort of patients (n = 1112).
End of follow-up for each F8 mutation is defined as the maximum number of exposure days to factor VIII concentrates observed during follow-up for at least 1 patient with this F8 mutation.
The risk is calculated by dividing the number of inhibitor patients with a specific mutation by the total number of patients with the same mutation that have a certain number of exposure days (eg, 20 or 50 exposure days).
Inhibitor risk is 0 at 50 ED because the patient with this mutation that developed an inhibitor did so after 95 exposure days.
One of the patients with the Arg593Cys mutation who developed an inhibitor also had a polymorphism in the promoter of the F8 gene (c.-112G > A).