Summary of positive data for IgM and/or IgG antibodies binding to FVIII, PEG-FVIII, or PEG, found in patients included in ≥1 of the 6 clinical studies
| Patient number . | Positive data for antibodies binding to indicated target antigen . | Temporal association of antibody detection with AEs∗ . | |||||
|---|---|---|---|---|---|---|---|
| FVIII . | PEG-FVIII . | PEG . | |||||
| IgM . | IgG . | IgM . | IgG . | IgM . | IgG . | ||
| 1 | N | N | ▲ | N | ▲ | N | No |
| 2 | N | N | N | X | N | N | No |
| 3 | N | N | N | ▲ | N | N | No |
| 4 | N | X | N | N | N | N | No |
| 5 | N | N | ▲ | N | ▲ | N | No |
| 6 | N | N | N | ▲ | N | N | No |
| 7 | N | N | N | X | N | N | No |
| 8 | N | N | N | ▲ | N | N | Yes |
| 9 | N | X | N | n.t. | N | N | No |
| 10 | N | N | N | X | N | N | No |
| 11 | N | X | N | n.t. | N | N | No |
| 12 | N | N | N | X | N | N | Yes |
| 13 | N | N | N | ▲ | N | N | Yes |
| 14 | N | ▲ | N | N | N | N | No |
| 15 | N | X | N | N | N | N | No |
| 16 | N | N | N | ▲ | N | N | Yes |
| 17 | N | N | N | ▲ | N | N | No |
| 18 | N | N | ▲ | N | N | N | Yes |
| 19 | N | N | ▲ | N | ▲ | N | Yes |
| 20 | N | N | N | X | N | N | Yes |
| 21 | N | N | N | X | N | N | No |
| 22 | ▲ | N | N | N | N | N | Yes |
| 23 | N | N | N | ▲ | N | N | No |
| 24 | N | X | N | ▲ | N | N | Yes |
| 25 | N | N | N | ▲ | N | N | No |
| 26 | N | N | ▲ | N | N | N | No |
| 27 | N | N | N | ▲ | N | N | No |
| 28 | N | N | N | ▲ | N | N | No |
| 29 | N | N | N | ▲ | N | N | No |
| 30 | N | N | N | ▲ | N | N | No |
| 31 | N | X | N | n.t. | N | N | No |
| 32 | N | X | N | X | N | N | Yes |
| 33 | N | N | N | ▲ | N | N | No |
| 34 | N | ▲ | N | n.t. | N | N | Yes |
| 35 | N | N | N | X | N | N | Yes |
| 36 | N | N | N | ▲ | N | N | No |
| 37 | N | N | N | ▲ | N | N | YES |
| 38 | N | N | N | X | N | N | No |
| 39 | N | N | ▲ | n.t. | N | N | No |
| 40 | N | X | N | ▲ | N | N | Yes |
| 41 | N | X | N | X | N | N | No |
| 42 | N | N | N | n.t. | ▲ | N | No |
| 43 | N | N | N | ▲ | N | N | Yes† |
| 44 | N | ▲ | N | ▲ | N | N | Yes† |
| 45 | N | N | N | n.t. | X | N | No |
| 46 | N | N | N | X | N | N | Yes |
| 47 | N | N | N | ▲ | N | N | Yes |
| 48 | N | N | N | X | N | N | Yes |
| 49 | N | N | N | ▲ | N | N | No |
| 50 | N | N | ▲ | ▲ | ▲ | N | No |
| 51 | N | X | N | X | N | N | No |
| 52 | N | ▲ | N | ▲ | N | N | No |
| 53 | N | N | N | N | ▲ | N | No |
| 54 | N | N | N | X | N | N | No |
| Patient number . | Positive data for antibodies binding to indicated target antigen . | Temporal association of antibody detection with AEs∗ . | |||||
|---|---|---|---|---|---|---|---|
| FVIII . | PEG-FVIII . | PEG . | |||||
| IgM . | IgG . | IgM . | IgG . | IgM . | IgG . | ||
| 1 | N | N | ▲ | N | ▲ | N | No |
| 2 | N | N | N | X | N | N | No |
| 3 | N | N | N | ▲ | N | N | No |
| 4 | N | X | N | N | N | N | No |
| 5 | N | N | ▲ | N | ▲ | N | No |
| 6 | N | N | N | ▲ | N | N | No |
| 7 | N | N | N | X | N | N | No |
| 8 | N | N | N | ▲ | N | N | Yes |
| 9 | N | X | N | n.t. | N | N | No |
| 10 | N | N | N | X | N | N | No |
| 11 | N | X | N | n.t. | N | N | No |
| 12 | N | N | N | X | N | N | Yes |
| 13 | N | N | N | ▲ | N | N | Yes |
| 14 | N | ▲ | N | N | N | N | No |
| 15 | N | X | N | N | N | N | No |
| 16 | N | N | N | ▲ | N | N | Yes |
| 17 | N | N | N | ▲ | N | N | No |
| 18 | N | N | ▲ | N | N | N | Yes |
| 19 | N | N | ▲ | N | ▲ | N | Yes |
| 20 | N | N | N | X | N | N | Yes |
| 21 | N | N | N | X | N | N | No |
| 22 | ▲ | N | N | N | N | N | Yes |
| 23 | N | N | N | ▲ | N | N | No |
| 24 | N | X | N | ▲ | N | N | Yes |
| 25 | N | N | N | ▲ | N | N | No |
| 26 | N | N | ▲ | N | N | N | No |
| 27 | N | N | N | ▲ | N | N | No |
| 28 | N | N | N | ▲ | N | N | No |
| 29 | N | N | N | ▲ | N | N | No |
| 30 | N | N | N | ▲ | N | N | No |
| 31 | N | X | N | n.t. | N | N | No |
| 32 | N | X | N | X | N | N | Yes |
| 33 | N | N | N | ▲ | N | N | No |
| 34 | N | ▲ | N | n.t. | N | N | Yes |
| 35 | N | N | N | X | N | N | Yes |
| 36 | N | N | N | ▲ | N | N | No |
| 37 | N | N | N | ▲ | N | N | YES |
| 38 | N | N | N | X | N | N | No |
| 39 | N | N | ▲ | n.t. | N | N | No |
| 40 | N | X | N | ▲ | N | N | Yes |
| 41 | N | X | N | X | N | N | No |
| 42 | N | N | N | n.t. | ▲ | N | No |
| 43 | N | N | N | ▲ | N | N | Yes† |
| 44 | N | ▲ | N | ▲ | N | N | Yes† |
| 45 | N | N | N | n.t. | X | N | No |
| 46 | N | N | N | X | N | N | Yes |
| 47 | N | N | N | ▲ | N | N | Yes |
| 48 | N | N | N | X | N | N | Yes |
| 49 | N | N | N | ▲ | N | N | No |
| 50 | N | N | ▲ | ▲ | ▲ | N | No |
| 51 | N | X | N | X | N | N | No |
| 52 | N | ▲ | N | ▲ | N | N | No |
| 53 | N | N | N | N | ▲ | N | No |
| 54 | N | N | N | X | N | N | No |
The 6 clinical studies, NCT01599819, NCT01736475, NCT02210091, NCT01913405, NCT01945593, and NCT02585960, are described in Table 1.
N, negative at all time points; n.t., not tested, no sample available; X, treatment-emerging antibodies detected after ≥1 exposure to rurioctocog alfa pegol; ▲, preexisting antibodies detected at screening.
AEs temporarily associated with the detection of antibodies binding to FVIII, PEG-FVIII, or PEG. Potential temporal associations between the detection of preexisting or treatment-emerging antibodies and the appearance of AEs were assessed considering the time period between the last negative antibody assessment before and the first negative antibody assessment after the occurrence of positive data for binding antibodies.
AEs experienced by patients 43 and 44 were considered to be related to treatment with rurioctocog alfa pegol.