Table 1. Characteristics of study cohort.
| Characteristic | Overall Cohort N=64 | Recurrent Inhibitor N=19 | No Recurrent Inhibitor N=45 | |
|---|---|---|---|---|
|
|
||||
| Median (Q1,Q3) N (%) |
Median (Q1,Q3) N (%) |
Median (Q1,Q3) N (%) |
p-value | |
| Demographics | ||||
| Age at inhibitor onset, y | 1.6 (1,3.3) | 1.2 (0.7,2.9) | 1.8 (1.1,3.5) | 0.20 |
| Age at start ITI, y | 3.3 (1.5,8.5) | 3.2 (1.1,6.8) | 3.3 (1.5,11.4) | 0.55 |
| Race | 0.74 | |||
| White | 46 (71.9) | 15 (78.9) | 31 (68.9) | |
| Black | 12 (18.8) | 3 (15.8) | 9 (20.0) | |
| Other | 6 (9.3) | 1 (5.3) | 5 (11.1) | |
| Hispanic ethnicity | 16 (25.0) | 6 (31.6) | 10 (22.2) | 0.53 |
| Hemophilia and health history | ||||
| Severe Hemophilia | 62 (96.9) | 18 (94.7) | 44 (97.8) | 1.0 |
| Family History of inhibitor | 13 (20.3) | 4 (21.1) | 9 (20.0) | 0.92 |
| F8 genotype (n=31) | 0.95 | |||
| High-risk | 25 (80.6) | 8 (80.0) | 17 (80.9) | |
| Low-risk | 6 (19.4) | 2 (20.0) | 4 (19.0) | |
| HIV positive | 3 (4.7) | 0 | 3 (6.7) | |
| Hepatitis C antibody positive | 6 (9.4) | 2 (10.5) | 4 (8.9) | 1.0 |
| Inhibitor characteristics | ||||
| Historical peak titer (BU/ml) | 9.9 (3.8,34) | 11.2 (3,38) | 8.5 (4.5,30) | 0.77 |
| Historical peak titer > 5 BU/ml | 43 (67.2) | 12 (63.1) | 31 (68.9) | 0.77 |
| Historical peak titer > 200 BU/ml | 3 (4.7) | 2 (10.5) | 1 (2.2) | 0.21 |
| Pre-ITI titer (BU/ml) | 2.1 (1,5.5) | 2.0 (1,4.5) | 2.5 (1,5.5) | 0.71 |
| Pre-ITI titer > 10 BU/ml | 5 (7.8) | 2 (10.5) | 3 (6.7) | 0.63 |
| Peak titer during ITI (BU/ml) | 2.8 (0.5,33) | 10 (0.6,40) | 2.7 (0.5,24) | 0.36 |
| Peak titer during ITI > 100 BU/ml | 6 (9.4) | 3 (15.8) | 3 (6.7) | 0.35 |
| Characteristics of ITI | ||||
| Time from inhibitor onset to start ITI, y | 0.75 (0.2,2.1) | 1.1 (0.4,2.4) | 0.6 (0.2,3.7) | 0.67 |
| ITI started 2 years after inhibitor onset | 14 (21.9) | 5 (26.3) | 9 (20.0) | 0.74 |
| First course of ITI | 61 (95.3) | 18 (94.7) | 43 (95.6) | 1.0 |
| ITI with recombinant FVIII product | 57 (89.1) | 17 (89.5) | 40 (88.9) | 0.95 |
| ITI regimen, FVIII infusions ≥ daily | 16 (84.2) | 34 (75.6) | 0.53 | |
| Dose of FVIII use for ITI < 100 IU/kg/day | 15 (23.4) | 3 (15.8) | 12 (26.7) | 0.52 |
| Any immunosuppression used during ITI | 5 (7.8) | 4 (21.1) | 1 (2.2) | 0.007 |
| Duration of ITI, y | 1.2 (0.6,2.0) | 0.75 (0.4,2.2) | 1.2 (0.6,2) | 0.42 |
| Tolerance criteria met | 0.71 | |||
| Negative titer/recovery > 66% | 36 (56.3) | 12 (63.2) | 24 (53.3) | |
| Negative titer/half-life > 6h | 1 (1.6) | 0 | 1 (2.2) | |
| Negative titer/recovery/half-life | 27 (42.2) | 7 (36.8) | 20 (44.4) | |
| FVIII Recovery % (n=63) | 85 (71,98) | 79 (74,85) | 89 (70,106) | 0.03† |
| FVIII half-life, hours (n=28) | 8 (6,9.1) | 7 (6,8) | 8 (6.4,9.2) | 0.18 |
| After ITI | ||||
| Not adherent to post ITI FVIII prophylaxis | 17 (26.6) | 5 (26.3) | 12 (26.7) | 0.78 |
| Events during 6 months before recurrent inhibitor or last negative inhibitor titer | 0.53 | |||
| Surgery | 12 (18.8) | 6 (31.6) | 6 (13.3) | 0.09 |
| Vaccination | 3 (4.7) | 0 | 3 (6.7) | |
| Serious bleed | 1 (1.6) | 0 | 1 (2.2) | |
| Infection | 3 (4.7) | 3 (15.8) | 0 | |
| Hospitalization | 1 (1.6) | 0 | 1 (2.2) | |
†
Kolmogorov-Smirnov two sample test. Y indicates years; BU indicates Bethesda unit; ITI indicates Immune tolerance induction; FVIII indicates factor VIII; h indicates hours;