Table 2.
Treatment characteristics for primary ITI
| Source | No. of participants | ITI regimen (%) | ITI Product (%) |
Age at inhibitor detection (mo) | Interval ID - ITI start (mo) | Age at ITI start, (mo) | No. of exposure d before inhibitor administration | Pre-ITI titer | Historical peak titer | Peak titer on ITI | Outcome (%) |
||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| pd | r | pd+r | CS | PS | F | ||||||||||
| Barnes [37] | 32 | 50 IU/kg 3-4x/wk (28); 100 IU/kg/d (72) |
6 | 88 | 6 | 25.2 (14.4-55.2) | 3.5 (0.3-19.2) | na | na | 3.3 (1.5-7.8) | 8.5 (4.3-67.8) | 13.5 (0-126.5) | 79.3 | na | 20.7 |
| Batorova [38] | 19 | 50 IU/kg 2x/d (for 2-3w), 50 IU/kg 3-4x/wk (42); 100 IU/kg 2x/d (58) |
68 | 32 | 0 | 22.8 (16.8-156) | na | 60 (18-180) | 25 (15-32) | 1.2 (0.6-3.4) | 7.8 (2.8-20) | 3.6 (1.9-4.6) | 78.9 | 10.5 | 5.3f |
| Callaghan [39] | 31 | 50 IU/kg 3-4x/wk (74); 50-250 IU/kg/d (26) |
26 | 68 | 6 | 13 (2-141b) | 13.3 (7.3-36.5) | 56.5 (16.4-139.7) | 7.5 (4.5-13.8) | 4.4 (1.3-22) | 34 (7.1-153) | 22 (2-139) | 71.0 | na | 29.0 |
| DiMichele [25] | 164 | Alternate day dosing (21); ≥100 IU/kg/d (47); ≥200 IU/kg/d (7) Unspecified (25) |
25 | 75 | 0 | na | 55.8e (0-256b) | 111.6e (1.2-768b) | na | CS/19.5 (0-230) F/61.3 (0-523) |
CS/130 (5-4833) F/571 (6-9999.5) |
CS/154 (0-1770) F/619 (34-3500) |
70.1 | na | 29.9 |
| Di Minno [40] | 137 | 50 IU/kg 3x/wk (24); 100 IU/kg/d (42); 200 IU/kg/d (34) |
27 | 73 | 0 | 30 (1-576) | 19 (<1-332) | 57.6 (6-702) | 15 (3->150) | 4.5 (0-200) | 64 (6-920) | na | 51.1 | 15.3 | 33.6 |
| Dou [41] | 110 | 100 IU/kg/d (7); 50 IU/kg/d (21); 50 IU/kg/ 1x/2d (72) |
82 | 16 | 3 | na | na | 72 (36-114) | na | na | na | na | 64.9 | na | 35.1 |
| El Alfy [42] | 10 | 25 IU/kg 3-4x/wk (40); 50 IU/kg 3-4x/wk (60) |
na | na | na | na | na | 66 (27-126) | 32 (18.8-95) | 43 (19.5-61.8) | 44.5 (25.5-62.5) | na | 80 | na | 20 |
| Elalfy [43] | 20 | 50 IU/kg 3x/wk | 100 | 0 | 0 | na | 8.5 (0.5-33) | 60 (36-144) | na | 36.5 (12-169) | 62 (2-412) | 41 (8-320) | 60 | 20 | 20 |
| Escobar [44] | 6 | 100 IU/kg/d | 100 | 0 | 0 | 84 (63-384) | NA | 402 (318-495) | na | 1.0 (0.6-13.5) | 33.4 (1.2-118.6) | na | 83.3 | na | 16.7 |
| Greninger [45] | 7 | ≤700 IU/kg/wk (57); 1400 IU/kg/wk (43); |
100 | 0 | 0 | 30 (12-97.5) | 16 (0-207.5) | 97.5 (28-264) | na | 5 (1.4-27) | 89 (5-200) | 10 (5-46) | 71.4 | 28.6 | 0 |
| Hay [21] | 115 | 50 IU/kg 3x/wk (50)††† 200 IU/kg/d (50)‡‡‡ |
11 | 89 | 0 | na | na | 15.6 (10.7-23.2)††† 14.4 (11.4-25.3)‡‡‡ |
na | 5.9 (3.3-7.3)††† 5.1 (3-7.4)‡‡‡ |
21.7 (13.4-52.5)††† 22.4 (12.5-50)‡‡‡ |
40.1 (7.6-150)††† 33 (1.5-205)‡‡‡ |
69.7 | 4.5 | 25.8 |
| Haya [46] | 42 | 140 IU/kg/d | 87 | 13 | 0 | na | 25 (12-78) | 84 (48.0-177) | 29 (3-250b) | 11 (5.5-30) | 76 (29.8-340) | na | 68.4 | 5.3 | 26.3 |
| Kreuz [47] | 48 | 50-100 IU/kg/d (13) 100 IU/kg 2x/d (88) |
100 | 0 | 0 | 37.2 (8.4-298.8b) | na | 69.6 (9.6-337.2b) | na | 12.5 (0.6-9736) | na | na | 70.8 | 8.3 | 20.8 |
| Kurth [30] | 8 | 50 IU/kg/d (13) 100-200 IU/kg/d (88) |
100 | 0 | 0 | 32 (17-41) | na | 41 (28.8-78.8) | na | 24.5 (1.8-73.5) | 250.5 (49.5-735.3) | na | 37.5 | 37.5 | 25 |
| Lapalud [48] | 15 | ≤450 IU/kg/wk (47) 700-1400 IU/kg/wk (53) |
27 | 73 | 0 | na | 7.1 (0.8-10.9) | 22.3 (14.6-46.2) | na | 10 (2.3-15) | 30 (12.5-181.3) | 241 (70-1334) | 46.7 | na | 53.3 |
| Lenk [49] | 140 | na | na | na | na | 132e | na | 154.8e | na | na | na | na | 78.6 | 8.7 | 12.7 |
| Lin [50] | 29 | 30-100 IU/kg/d to 3-4x/wk | 0 | 100 | 0 | na | HR 36 (12.5-49) | 204 (7.2-540) 306 (19.2-540) |
na | 0.85 (0.6-1.6)e 5 (2.8-367.5) |
40 (16-49) | 1.0 (0.7-3.3)e 15 (5.8-442) |
84.6 | 11.5 | 3.8 |
| Mariani [51] | 314 | <50 IU/kg/d (25) 50-99 IU/kg/d (23) 100-199 IU/kg/d (20) ≥200 IU/kg/d (32) |
88 | 12 | 0 | 48 (<12-768b) | 17 (<1-379b) | na | na | 7 (0-720b) | 54 (1-25,000b) | na | 44.6 | 7.3 | 21.0g |
| Nakar [52] | 58 | ≥100 IU/kg/d | 26 | 74 | 0 | 18 (1.3-603.6b) | na | na | na | na | na | na | 88 | na | 12 |
| Nogami [31] | 155 | ≤75 IU/kg 3x/wk (52); ≥90 IU/kg/d (12); Other (30) Unclassified (5) |
13 | 87 | 0 | 14.4 (10.8-25.2) | 7.2 (2.4-26.4) | na | NA | 3.9 (1.7-7.9) | 14 (3.7-46) | na | 60.6 | na | 24.5h |
| Oldenburg [53] | 32c 9d |
<100 IU/kg/d (22)a ≥100 IU/kg/d (78)a |
100 | 0 | 0 | na | na | 20.4 (0.7-206.4b)c 422.4 (277.2-638.4b)d |
na | 5.7 (0.7-831b)c 7.4 (1.0-109b)d |
20 (1.7-6842b)c 73 (11.2-737b)d |
na | 63.4 | 24.4 | 12.2 |
| Rivard [54] | 32 | <85 IU/kg/d (34) ≥85 IU/kg/d (66) |
0 | 100 | 0 | 12 (0-48b) | 8.7 (0.2-38.9b) | 24 (0-60b) | 13.5 | na | na | na | 68.8 | na | 31.2 |
| Rocino [55] | 71 | 50-≥200 IU/kg/d to 3-4x/wk | 17 | 83 | 0 | 20.4 (2.6-492b) | na | 45.6 (5.3-492.2b) | 15 (2-43b) | 4 (0-165b) | 18.5 (0.8-704b) | 43 (0.5-16,384b) | 71.8 | 12.7 | 15.5 |
| Ryu [56] | 17 | <25 IU/kg 3x/wk (6); <50 IU/kg/d (6); 75-100 IU/kg 3x/wk (65); 90-110 IU/kg/d (24) |
65 | 24 | 12 | 24 (12-36) | 57.6 (29.4-109.8) | 69.6 (44.4-148.8) | 16 (12-47) | 3.7 (2.1-5.9) | 30.8 (12.6-56.8) | 14.4 (3.3-39.6) | 82.4 | 5.9 | 11.8 |
| Salviato [24] | 16 | na | na | na | na | na | na | na | na | 4.4 (1.5-8) | 300 (72-976) | na | 68.8 | na | 31.3 |
| Ter Avest [57] | 21 | 25-50 IU/kg 2-4x/wk (86); From LD to HD (14) |
48 | 52 | 0 | 19 (13.5-28) | na | na | 17 (10.5-35) | 4.5 (2.5-14.8) | na | 4.6 (1.7-16.4) | 85.7 | na | 14.3 |
| Unuvar [58] | 21 | 20-50 IU/kg 2x/wk (57); 50 IU/kg 3x/wk (5); 50 IU/kg 3x/wk; HD VWF/FVIII (5); 25 IU/kg 3x/wk (10); 30 IU/kg 3x/wk (19); Dutch protocol (5) |
100 | 0 | 0 | na | 2.5 (0.3-60b) | 108 (42-138) | 25 (14-64.5) | 19.2 (3.6-515b) | 80 (6-517b) | 27 (2.5-517b) | 26.3 | 36.8 | 36.8 |
Numbers are reported as median (IQR), unless states otherwise.
CS, complete success; F, failure; H, high dose; HR, high-responding inhibitor ≥5 BU/mL; IU, international unit; ITI, immune tolerance induction; kg, kilogram; L, low dose; LR, low-responding inhibitor <5 BU/mL; na, not available; PS, partial success; pd, plasma-derived FVIII; r, recombinant FVIII; pd+r, plasma-derived and recombinant FVIII.
a
Both primary and rescue ITI.
b
Range.
c
Children.
d
Adults.
e
Reported numbers of the largest group.
f
One person died while on ITI, therefore the ITI outcome is not available in 5.3%.
g
Data was insufficient to evaluate ITI outcome in 37 persons (11.8%) and ITI was ongoing in 48 persons (15.3%).
h
ITI was ongoing in 23 patients (14.8%).