Table 1.
| Patient |
FVIII genotype |
Inhibitor titre (BU/mL) | Factor brand being used when inhibitor developed | rFVIIIFc ITI regimen | Time (weeks) | Current titre (BU/mL) | Current status | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Historical peak (pre‐ITI) | Immediately pre‐rFVIIIFc ITI | Weekly factor usage (IU/kg) | Inhibitor diagnosis to start of rFVIIIFc ITI | From start of ITI to | Duration of rFVIIIFc ITI | |||||||||
| Negative Bethesda titre § | Normal recovery ¶ | Half‐life ≥6 h ‡‡ | Tolerization ‡‡ | |||||||||||
| 1‐9 §§ | Intron−22 | 38.4 | 20.8 | rFVIIIFc (Eloctate, Sanofi, Waltham, MA) | 200 IU/kg q.d. | 1400 | 6 | 3 | NR | 3 | 3 | 3 | Negative | rFVIIIFc prophylaxis |
| 1‐1 | Missense | 51.7 | 51.7 | rFVIIIFc (Eloctate, Sanofi, Waltham, MA) | 85 IU/kg q.d. | 595 | 11 | 4 | 10 | 21 | 21 | 21 | Negative | rFVIIIFc prophylaxis |
| 1‐8 §§ | Intron−22 | 25.6 | 25.6 | rFVIIIFc (Eloctate, Sanofi, Waltham, MA) | 200 IU/kg q.d. | 1400 | 18 | 9 | NR | 21 | 21 | 23 | Negative | rFVIIIFc prophylaxis |
| 1‐2 | Frameshift | 150.9 | 106.9 | pdFVIII (Alphanate, Grifols Biologicals LLC, Los Angeles, CA) | 110 IU/kg q.d. | 770 | 12 | 24 | NR | 29 | 29 | 30 | Negative | rFVIIIFc prophylaxis |
| 1‐5 | Intron−22 | 376.0 | 32.0 | rFVIII (Advate, Baxalta US Inc, Lexington, MA) | 100 IU/kg q.d. | 700 | 41 | 30 | 56 | NR | 30 | 64 | Negative | rFVIIIFc prophylaxis |
| 1‐3 | Unknown | 1126.0 | 1126.0 | rFVIII (Advate, Baxalta US Inc, Lexington, MA) | 200 IU/kg q.d. | 1400 | 1 | 31 | NR | 40 | 40 | 40 | Negative | rFVIIIFc prophylaxis |
| 1‐7 ¶¶ , ††† | Intron−22 | 3.0 ‡‡‡ | 3.0 | rFVIIIFc (Eloctate, Sanofi, Waltham, MA) | 83 IU/kg q.d. | 581 | 0 | 41 | NR | NR | 59 | 71 | Negative | rFVIIIFc prophylaxis |
| 1‐4 §§§ | Intron−22 | 11.0 | 11.0 | rFVIII (Xyntha, Pfizer, Philadelphia, PA) | 50 IU/kg t.i.w. | 150 | 4 | 64 | 112 | 112 | 64 | 64 | Negative | rFVIIIFc prophylaxis |
| 1‐6 | Intron−22 | 378.7 | 378.1 | rFVIII (Advate, Baxalta US Inc, Lexington, MA) | 96 IU/kg q.d. | 672 | 1 | 99 | N/A | N/A | 99 | 157 | 1.3 ¶¶¶ | rFVIIIFc ITI |
| 1‐10 §§ | Insertion | 28.8 | 6.2 | Missing data | 100 IU/kg q.d. | 700 | 6 | N/A | N/A | N/A | N/A | 59 | 4.4 | rFVIIIFc ITI |
Abbreviations: BU, Bethesda unit; FVIII, factor VIII; ITI, immune tolerance induction; N/A, not applicable; NR, not reported; q.d., once daily; rFVIIIFc, recombinant factor VIII Fc fusion protein; t.i.w., three times per week.
Patients are sorted in ascending order according to time from the start of ITI to tolerization. Patient numbers were randomly assigned.
Bolded data indicate high‐risk features.
Time to first negative inhibitor titre: time interval (in weeks) from the start date of ITI treatment with rFVIIIFc to date of the patient's first time reaching inhibitor titre of <0.6 BU/mL.
Time to FVIII normal recovery: time interval (in weeks) from the date of ITI treatment with rFVIIIFc to date of the patient's first time reaching FVIII recovery level of ≥66% of expected.
Time to FVIII half‐life of ≥6 hours: time interval (in weeks) from the start date of ITI treatment with rFVIIIFc to date of the patient's first time reaching FVIII half‐life of ≥6 hours.
Time to tolerization: time interval (in weeks) from the start date of ITI treatment with rFVIIIFc to the date when physician reported this patient reached tolerization.
Newly identified patient.
Received rituximab concomitantly with rFVIIIFc.
This patient was first on rFVIIIFc ITI (83 IU/kg q.d.) for 15 weeks (titre=26 BU/mL), switched away to another factor ITI for 13 weeks and then restarted rFVIIIFc ITI on 29 March 2017 (titre=44 BU/mL) with rFVIIIFc 21 IU/kg per hour drip treatment regimen, and achieved negative inhibitor titre 13 weeks after restart of rFVIIIFc ITI and was tolerized after 32 weeks of treatment; patient is currently on rFVIIIFc prophylaxis.
This patient was enrolled with a historical peak inhibitor titre of 30.0 BU/mL. During the final data cleaning, the value was corrected to be 3.0 BU/mL instead.
This patient transitioned to rFVIIIFc prophylaxis after 64 weeks of rFVIIIFc ITI treatment, laboratory assessments on normal recovery and time to half‐life ≥6 hours were available 58 weeks after the patient transitioned to rFVIIIFc prophylaxis.
This patient was considered tolerized by the treating physician but showed a low‐titre inhibitor during the follow‐up period and remains on rFVIIIFc ITI at the time of data capture.