Risk factors for inhibitor development and inhibitor characteristics
| . | All patients (n = 407) . | Advate (n = 172) . | Kogenate Bayer/Helixate NexGen (n = 128) . | ReFacto (n = 52) . | ReFacto AF (n = 44) . | Recombinate (n = 11) . |
|---|---|---|---|---|---|---|
| Risk factors for FVIII inhibitor development | ||||||
| Ethnicity, n (%) | ||||||
| White | 354 (87) | 147 (85) | 112 (88) | 44 (85) | 41 (93) | 10 (91) |
| Nonwhite | 53 (13) | 25 (15) | 16 (12) | 8 (15) | 3 (7) | 1 (9) |
| Not known | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Age at first treatment, mo | ||||||
| Median | 9 | 9 | 10 | 7* | 10 | 9 |
| IQR | 4-13 | 2-13 | 5-15 | 3-10 | 7-13 | 2-15 |
| Range | 0-95 | 0-95 | 0-52 | 0-31 | 0-64 | 1-18 |
| Not known, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| FVIII mutation, n (%)1 | ||||||
| High risk (including inversions) | 244 (60.0) | 103 (59.9) | 71 (55.5) | 35 (67.3) | 28 (63.6) | 7 (63.6) |
| Low risk | 133 (32.7) | 56 (32.6) | 48 (37.5) | 14 (26.9) | 12 (27.3) | 3 (27.3) |
| Not known | 30 (7.4) | 13 (7.6) | 9 (7.0) | 3 (5.8) | 4 (9.1) | 1 (9.1) |
| Inversions | 189 (50.1) | 79 (49.7) | 55 (46.2) | 28 (57.1) | 21 (52.5) | 6 (60) |
| High risk, excluding inversions | 55 (14.6) | 24 (15.1) | 16 (13.5) | 7 (14.3) | 7 (17.5) | 1 (10) |
| FH of hemophilia, n (%) | ||||||
| Yes | 232 (57.0) | 100 (58.1) | 77 (60.2) | 29 (55.8) | 20 (45.5) | 6 (54.6) |
| No | 174 (42.8) | 72 (41.9) | 51 (39.8) | 22 (42.3) | 24 (54.5) | 5 (45.4) |
| Not known | 1 (0.3) | 0 (0) | 0 (0) | 1 (1.9) | 0 (0) | 0 (0.0) |
| FH of a FVIII inhibitor of those with an FH of hemophilia, n (%) | ||||||
| Yes | 41 (17.7) | 15 (15) | 18 (23.4) | 7 (24.1) | 0 (0)** | 1 (17) |
| No | 190 (82.0) | 84 (84) | 59 (76.6) | 22 (75.9) | 20 (100) | 5 (83) |
| Not known | 1 (0.4) | 1 (1) | 0 (0.0) | 0 (0) | 0 (0) | 0 (0.0) |
| Intensive treatment at first exposure, n (%) | ||||||
| Yes | 56 (13.8) | 26 (15.1) | 17 (13.3) | 7 (13.5) | 4 (9.1) | 2 (18.2) |
| No | 343 (84.3) | 143 (83.1) | 108 (84.4) | 43 (82.7) | 40 (90.9) | 9 (81.8) |
| Not known | 8 (2.0) | 3 (1.7) | 3 (2.3) | 2 (3.9) | 0 (0.0) | 0 (0.0) |
| Intensive treatment during first 50 EDs (excluding first exposure) before inhibitor development, n (%) | ||||||
| Yes | 175 (43.0) | 73 (42.4) | 48 (37.5) | 28 (53.9) | 20 (45.5) | 6 (54.5) |
| No | 219 (53.8) | 94 (54.7) | 75 (58.6) | 22 (42.3) | 23 (52.3) | 5 (45.5) |
| Not known | 13 (3.2) | 5 (2.9) | 5 (3.9) | 2 (3.9) | 1 (2.3) | 0 (0.0) |
| Characteristics of FVIII inhibitors | ||||||
| Inhibitors reported, n (%) | ||||||
| All | 118 (29.0) | 42 (24.4) | 45 (35.2) | 12 (23.1) | 15 (34.1) | 4 (36.4) |
| High titer | 60 (14.7) | 19 (11.0) | 25 (19.5) | 10 (19.2) | 3 (6.8) | 3 (27.3) |
| Low titer | 58 (14.3) | 23 (13.4) | 20 (15.6) | 2 (3.9) | 12 (27.3) | 1 (9.1) |
| Peak inhibitor titer | ||||||
| Median | 5.0 | 4.7 | 6.9 | 24.6 | 2.8 | 17.3 |
| IQR | 1.2-27.6 | 1-19.5 | 1.7-28.8 | 5.25-90.5 | 1.1-4.9 | 3.2-35.8 |
| Range | 0.07-1562 | 0.07-1562 | 0.4-402 | 0.5-222 | 0.5-86.6 | 0.3-40.1 |
| Not known, n (%) | 1 (0.85) | 1 (2.38) | 0 (0.0) | 0 (0.0) | 0 (0) | |
| EDs to inhibitor formation | ||||||
| Median | 16 | 17.5 | 15 | 28.5 | 9 | 6 |
| IQR | 9-30 | 10.25-27.75 | 8-31 | 19-55.75 | 7-16 | 4-8 |
| Range | 1-442 | 1-358 | 2-106 | 12-442 | 5-52 | 4-8 |
| Not known, n (%) | 7/118 (6) | 2/42 (4.8) | 2/45 (4.4) | 2/12 (16.7) | 0/15 (0.0) | 1/4 (25) |
| Follow-up for patients not developing an inhibitor, mo | ||||||
| Median | 45.0 | 49.5 | 36.0 | 59.2 | 18.0 | 12.0 |
| IQR | 24.0-61.7 | 36.0-61.5 | 16.0-69.0 | 36.0-115.5 | 12.0-27.9 | 6.0-30.0 |
| Range | 1.61-154.48 | 1.61-106.48 | 2.96-142.49 | 6.01–154.48 | 2.25-38.97 | 6.01-36.01 |
| Not known, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Patients reported in RODIN study, n (%) | 88 (22) | 48 (28) | 21 (16.4) | 12 (23) | 5 (11) | 2 (18) |
| Inhibitors reported in RODIN participants, n (%) | ||||||
| High titer | 17 (19.3) | 5 (10.4) | 6 (28.6) | 4 (33.3) | 0 (0.0) | 2 (100) |
| Low titer | 16 (18.2) | 8 (16.7) | 4 (19.1) | 1 (8.3) | 3 (60.0) | 0 (0) |
| All | 33 (37.5) | 13 (27.1) | 10 (47.6) | 5 (41.7) | 3 (60.0) | 2 (100) |
| . | All patients (n = 407) . | Advate (n = 172) . | Kogenate Bayer/Helixate NexGen (n = 128) . | ReFacto (n = 52) . | ReFacto AF (n = 44) . | Recombinate (n = 11) . |
|---|---|---|---|---|---|---|
| Risk factors for FVIII inhibitor development | ||||||
| Ethnicity, n (%) | ||||||
| White | 354 (87) | 147 (85) | 112 (88) | 44 (85) | 41 (93) | 10 (91) |
| Nonwhite | 53 (13) | 25 (15) | 16 (12) | 8 (15) | 3 (7) | 1 (9) |
| Not known | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Age at first treatment, mo | ||||||
| Median | 9 | 9 | 10 | 7* | 10 | 9 |
| IQR | 4-13 | 2-13 | 5-15 | 3-10 | 7-13 | 2-15 |
| Range | 0-95 | 0-95 | 0-52 | 0-31 | 0-64 | 1-18 |
| Not known, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| FVIII mutation, n (%)1 | ||||||
| High risk (including inversions) | 244 (60.0) | 103 (59.9) | 71 (55.5) | 35 (67.3) | 28 (63.6) | 7 (63.6) |
| Low risk | 133 (32.7) | 56 (32.6) | 48 (37.5) | 14 (26.9) | 12 (27.3) | 3 (27.3) |
| Not known | 30 (7.4) | 13 (7.6) | 9 (7.0) | 3 (5.8) | 4 (9.1) | 1 (9.1) |
| Inversions | 189 (50.1) | 79 (49.7) | 55 (46.2) | 28 (57.1) | 21 (52.5) | 6 (60) |
| High risk, excluding inversions | 55 (14.6) | 24 (15.1) | 16 (13.5) | 7 (14.3) | 7 (17.5) | 1 (10) |
| FH of hemophilia, n (%) | ||||||
| Yes | 232 (57.0) | 100 (58.1) | 77 (60.2) | 29 (55.8) | 20 (45.5) | 6 (54.6) |
| No | 174 (42.8) | 72 (41.9) | 51 (39.8) | 22 (42.3) | 24 (54.5) | 5 (45.4) |
| Not known | 1 (0.3) | 0 (0) | 0 (0) | 1 (1.9) | 0 (0) | 0 (0.0) |
| FH of a FVIII inhibitor of those with an FH of hemophilia, n (%) | ||||||
| Yes | 41 (17.7) | 15 (15) | 18 (23.4) | 7 (24.1) | 0 (0)** | 1 (17) |
| No | 190 (82.0) | 84 (84) | 59 (76.6) | 22 (75.9) | 20 (100) | 5 (83) |
| Not known | 1 (0.4) | 1 (1) | 0 (0.0) | 0 (0) | 0 (0) | 0 (0.0) |
| Intensive treatment at first exposure, n (%) | ||||||
| Yes | 56 (13.8) | 26 (15.1) | 17 (13.3) | 7 (13.5) | 4 (9.1) | 2 (18.2) |
| No | 343 (84.3) | 143 (83.1) | 108 (84.4) | 43 (82.7) | 40 (90.9) | 9 (81.8) |
| Not known | 8 (2.0) | 3 (1.7) | 3 (2.3) | 2 (3.9) | 0 (0.0) | 0 (0.0) |
| Intensive treatment during first 50 EDs (excluding first exposure) before inhibitor development, n (%) | ||||||
| Yes | 175 (43.0) | 73 (42.4) | 48 (37.5) | 28 (53.9) | 20 (45.5) | 6 (54.5) |
| No | 219 (53.8) | 94 (54.7) | 75 (58.6) | 22 (42.3) | 23 (52.3) | 5 (45.5) |
| Not known | 13 (3.2) | 5 (2.9) | 5 (3.9) | 2 (3.9) | 1 (2.3) | 0 (0.0) |
| Characteristics of FVIII inhibitors | ||||||
| Inhibitors reported, n (%) | ||||||
| All | 118 (29.0) | 42 (24.4) | 45 (35.2) | 12 (23.1) | 15 (34.1) | 4 (36.4) |
| High titer | 60 (14.7) | 19 (11.0) | 25 (19.5) | 10 (19.2) | 3 (6.8) | 3 (27.3) |
| Low titer | 58 (14.3) | 23 (13.4) | 20 (15.6) | 2 (3.9) | 12 (27.3) | 1 (9.1) |
| Peak inhibitor titer | ||||||
| Median | 5.0 | 4.7 | 6.9 | 24.6 | 2.8 | 17.3 |
| IQR | 1.2-27.6 | 1-19.5 | 1.7-28.8 | 5.25-90.5 | 1.1-4.9 | 3.2-35.8 |
| Range | 0.07-1562 | 0.07-1562 | 0.4-402 | 0.5-222 | 0.5-86.6 | 0.3-40.1 |
| Not known, n (%) | 1 (0.85) | 1 (2.38) | 0 (0.0) | 0 (0.0) | 0 (0) | |
| EDs to inhibitor formation | ||||||
| Median | 16 | 17.5 | 15 | 28.5 | 9 | 6 |
| IQR | 9-30 | 10.25-27.75 | 8-31 | 19-55.75 | 7-16 | 4-8 |
| Range | 1-442 | 1-358 | 2-106 | 12-442 | 5-52 | 4-8 |
| Not known, n (%) | 7/118 (6) | 2/42 (4.8) | 2/45 (4.4) | 2/12 (16.7) | 0/15 (0.0) | 1/4 (25) |
| Follow-up for patients not developing an inhibitor, mo | ||||||
| Median | 45.0 | 49.5 | 36.0 | 59.2 | 18.0 | 12.0 |
| IQR | 24.0-61.7 | 36.0-61.5 | 16.0-69.0 | 36.0-115.5 | 12.0-27.9 | 6.0-30.0 |
| Range | 1.61-154.48 | 1.61-106.48 | 2.96-142.49 | 6.01–154.48 | 2.25-38.97 | 6.01-36.01 |
| Not known, n (%) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 (0) |
| Patients reported in RODIN study, n (%) | 88 (22) | 48 (28) | 21 (16.4) | 12 (23) | 5 (11) | 2 (18) |
| Inhibitors reported in RODIN participants, n (%) | ||||||
| High titer | 17 (19.3) | 5 (10.4) | 6 (28.6) | 4 (33.3) | 0 (0.0) | 2 (100) |
| Low titer | 16 (18.2) | 8 (16.7) | 4 (19.1) | 1 (8.3) | 3 (60.0) | 0 (0) |
| All | 33 (37.5) | 13 (27.1) | 10 (47.6) | 5 (41.7) | 3 (60.0) | 2 (100) |
Patients first treated with ReFacto received their first treatment at a younger age than other brands of rFVIII (*P = .047), and those first treated with ReFacto AF were less likely to have had a FH of an inhibitor (**P = .04). There were no other statistically significant differences in characteristics between the groups, and this included genotype, whether defined as in “Methods” or if inversions were excluded from the high-risk group.