Risk of inhibitor development according to patient characteristics
| . | All inhibitors . | High-titer inhibitors* . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Proportion with Inh (%) . | Crude RR (CI) . | P . | Adjusted RR (CI) . | P . | No. of Inh (%) . | Crude RR (CI) . | P . | Adjusted RR (CI) . | P . | |
| Baseline factor VIII activity | ||||||||||
| 0.01 to 0.02 IU/mL | 4/34 (12) | 1.0 | 1.0† | 2/34 (6) | 1.0 | .07 | 1.0† | |||
| Less than 0.01 IU/mL | 83/332 (25) | 2.3 (0.9-6.3) | .10 | 4.1 (1.0-16.9) | .05 | 67/332 (20) | 3.8 (0.9-15.3) | 6.5 (0.9-47.5) | .06 | |
| Ethnicity | ||||||||||
| White | 78/327 (24) | 1.0 | 1.0‡ | 63/327 (19) | 1.0 | 1.0‡ | ||||
| African | 3/8 (38) | 1.8 (0.6-5.8) | .31 | 1.9 (0.6-6.1) | .31 | 2/8 (25) | 1.5 (0.4-6.2) | .57 | 1.4 (0.3-6.1) | .62 |
| Asian | 1/15 (7) | 0.3 (0.04-1.9) | .19 | 0.3 (0.04-2.4) | .27 | 1/15 (7) | 0.3 (0.05-2.4) | .27 | 0.4 (0.05-2.8) | .35 |
| Other | 5/15 (33) | 1.5 (0.6-3.6) | .42 | 2.5 (1.0-6.7) | .06 | 3/15 (20) | 1.1 (0.3-3.4) | .89 | 1.7 (0.5-5.7) | .41 |
| Family history of hemophilia | ||||||||||
| Negative | 45/191 (24) | 1.0 | 1.0‡ | 36/191 (19) | 1.0 | 1.0‡ | ||||
| Positive | 42/168 (25) | 1.1 (0.7-1.6) | .69 | 1.0 (0.7-1.6) | .88 | 33/168 (20) | 1.1 (0.7-1.7) | .78 | 1.0 (0.6-1.7) | .85 |
| Family history of inhibitors | ||||||||||
| Negative | 29/138 (21) | 1.0 | 1.0‡ | 21/138 (15) | 1.0 | 1.0‡ | ||||
| Positive | 13/24 (52) | 3.1 (1.6-6.0) | .001 | 2.8 (1.3-6.1) | .007 | 12/24 (50) | 4.0 (2.0-8.2) | < .001 | 3.5 (1.5-8.1) | .003 |
| Breastfeeding | ||||||||||
| No | 12/41 (29) | 1.0 | 1.0§ | 8/41 (20) | 1.0 | 1.0§ | ||||
| Yes | 25/91 (27) | 0.9 (0.5-1.9) | .88 | 1.3 (0.6-2.8) | .59 | 23/91 (25) | 1.3 (0.6-1.9) | .51 | 2.1 (0.8-5.5) | .12 |
| Factor VIII gene mutation type | ||||||||||
| Low risk | 13/100 (13) | 1.0 | 1.0∥ | 7/100 (7) | 1.0 | 1.0∥ | ||||
| High risk | 68/212 (32) | 2.8 (1.5-5.0) | .001 | 2.3 (1.3-4.3) | .006 | 57/212 (27) | 4.3 (2.0-9.5) | < .001 | 3.7 (1.7-8.3) | .001 |
| . | All inhibitors . | High-titer inhibitors* . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Proportion with Inh (%) . | Crude RR (CI) . | P . | Adjusted RR (CI) . | P . | No. of Inh (%) . | Crude RR (CI) . | P . | Adjusted RR (CI) . | P . | |
| Baseline factor VIII activity | ||||||||||
| 0.01 to 0.02 IU/mL | 4/34 (12) | 1.0 | 1.0† | 2/34 (6) | 1.0 | .07 | 1.0† | |||
| Less than 0.01 IU/mL | 83/332 (25) | 2.3 (0.9-6.3) | .10 | 4.1 (1.0-16.9) | .05 | 67/332 (20) | 3.8 (0.9-15.3) | 6.5 (0.9-47.5) | .06 | |
| Ethnicity | ||||||||||
| White | 78/327 (24) | 1.0 | 1.0‡ | 63/327 (19) | 1.0 | 1.0‡ | ||||
| African | 3/8 (38) | 1.8 (0.6-5.8) | .31 | 1.9 (0.6-6.1) | .31 | 2/8 (25) | 1.5 (0.4-6.2) | .57 | 1.4 (0.3-6.1) | .62 |
| Asian | 1/15 (7) | 0.3 (0.04-1.9) | .19 | 0.3 (0.04-2.4) | .27 | 1/15 (7) | 0.3 (0.05-2.4) | .27 | 0.4 (0.05-2.8) | .35 |
| Other | 5/15 (33) | 1.5 (0.6-3.6) | .42 | 2.5 (1.0-6.7) | .06 | 3/15 (20) | 1.1 (0.3-3.4) | .89 | 1.7 (0.5-5.7) | .41 |
| Family history of hemophilia | ||||||||||
| Negative | 45/191 (24) | 1.0 | 1.0‡ | 36/191 (19) | 1.0 | 1.0‡ | ||||
| Positive | 42/168 (25) | 1.1 (0.7-1.6) | .69 | 1.0 (0.7-1.6) | .88 | 33/168 (20) | 1.1 (0.7-1.7) | .78 | 1.0 (0.6-1.7) | .85 |
| Family history of inhibitors | ||||||||||
| Negative | 29/138 (21) | 1.0 | 1.0‡ | 21/138 (15) | 1.0 | 1.0‡ | ||||
| Positive | 13/24 (52) | 3.1 (1.6-6.0) | .001 | 2.8 (1.3-6.1) | .007 | 12/24 (50) | 4.0 (2.0-8.2) | < .001 | 3.5 (1.5-8.1) | .003 |
| Breastfeeding | ||||||||||
| No | 12/41 (29) | 1.0 | 1.0§ | 8/41 (20) | 1.0 | 1.0§ | ||||
| Yes | 25/91 (27) | 0.9 (0.5-1.9) | .88 | 1.3 (0.6-2.8) | .59 | 23/91 (25) | 1.3 (0.6-1.9) | .51 | 2.1 (0.8-5.5) | .12 |
| Factor VIII gene mutation type | ||||||||||
| Low risk | 13/100 (13) | 1.0 | 1.0∥ | 7/100 (7) | 1.0 | 1.0∥ | ||||
| High risk | 68/212 (32) | 2.8 (1.5-5.0) | .001 | 2.3 (1.3-4.3) | .006 | 57/212 (27) | 4.3 (2.0-9.5) | < .001 | 3.7 (1.7-8.3) | .001 |
Inh indicates inhibitors.
*High-titer inhibitor was defined as a clinically relevant inhibitor with inhibitor titers of at least 5 Bethesda units/mL at any time.
†Adjusted for ethnicity, factor VIII gene mutation type, age at first exposure, duration between exposure days, dose, prophylaxis, and product type.
‡Adjusted for baseline factor VIII activity level, factor VIII gene mutation type, age at first exposure, duration between exposure days, dose, prophylaxis, and product type.
§Adjusted for baseline factor VIII activity level, ethnicity, factor VIII gene mutation type, age at first exposure, duration between exposure days, dose, prophylaxis, and product type.
∥Adjusted for baseline factor VIII activity level, ethnicity, age at first exposure, duration between exposure days, dose, prophylaxis, and product type.