Characteristics of pediatric patients with ITP who developed postbaseline anti-romiplostim neutralizing antibodies in clinical trials
| Patient no. (n = 8) . | At first detection of anti-romiplostim neutralizing antibodies . | After first detection of anti-romiplostim antibodies . | |||||
|---|---|---|---|---|---|---|---|
| Treatment week . | Platelet count (×109/L) . | Romiplostim dose (µg/kg) . | Cumulative romiplostim dose (µg/kg) . | AEs* . | Received romiplostim . | Platelet response n1/N1 (%)† . | |
| Transient antibodies (n = 4)‡ | |||||||
| 10 | 99 | 36 | 6 | 745 | — | Yes | 20/39 (51) |
| 13§ | 51 | 146 | 10 | 320 | — | Yes | 26/31 (84) |
| 19§ | 12 | 25 | 8 | 47 | Bleeding: contusion, petechiae at week 12ǁ | Yes | 0/57 (0) |
| 24§ | 76 | 52 | 7 | 389 | — | Yes | 25/37 (68) |
| Persistent antibodies (n = 4)¶ | |||||||
| 5 | 75 | — | — | 675 | — | No | — |
| 11 | 52 | 77 | 10 | 469 | — | Yes | 11/17 (65) |
| 12# | 52 | 387 | 5 | 242 | — | Yes | 42/48 (88) |
| 25# | 76 | 61 | 5 | 295 | Bleeding (epistaxis at week 101 and 124; contusion at week 148) | Yes | 78/81 (96) |
| Median | 64 | 61 | 7 | 354 | — | — | 100% |
| Range | 12-99 | 25-387 | 5-10 | 47-745 | — | — | 2%-100% |
| Patient no. (n = 8) . | At first detection of anti-romiplostim neutralizing antibodies . | After first detection of anti-romiplostim antibodies . | |||||
|---|---|---|---|---|---|---|---|
| Treatment week . | Platelet count (×109/L) . | Romiplostim dose (µg/kg) . | Cumulative romiplostim dose (µg/kg) . | AEs* . | Received romiplostim . | Platelet response n1/N1 (%)† . | |
| Transient antibodies (n = 4)‡ | |||||||
| 10 | 99 | 36 | 6 | 745 | — | Yes | 20/39 (51) |
| 13§ | 51 | 146 | 10 | 320 | — | Yes | 26/31 (84) |
| 19§ | 12 | 25 | 8 | 47 | Bleeding: contusion, petechiae at week 12ǁ | Yes | 0/57 (0) |
| 24§ | 76 | 52 | 7 | 389 | — | Yes | 25/37 (68) |
| Persistent antibodies (n = 4)¶ | |||||||
| 5 | 75 | — | — | 675 | — | No | — |
| 11 | 52 | 77 | 10 | 469 | — | Yes | 11/17 (65) |
| 12# | 52 | 387 | 5 | 242 | — | Yes | 42/48 (88) |
| 25# | 76 | 61 | 5 | 295 | Bleeding (epistaxis at week 101 and 124; contusion at week 148) | Yes | 78/81 (96) |
| Median | 64 | 61 | 7 | 354 | — | — | 100% |
| Range | 12-99 | 25-387 | 5-10 | 47-745 | — | — | 2%-100% |
MedDRA, Medical Dictionary for Regulatory Activities.
Bleeding AEs (defined as at least 1 event from MedDRA hemorrhages [Standardized MedDRA Query]) or hypersensitivity AEs (defined as at least 1 event from the Standardized MedDRA Queries for anaphylactic reaction, anaphylactic-anaphylactoid shock conditions, angioedema, or hypersensitivity) that started or worsened within 30 days after antibody detection (within 30 days of the date of collection of a sample that tested positive for antibodies).
Platelet response was defined as a weekly platelet count ≥50 × 109/L during the treatment period without a rescue medication in the past 4 weeks (n1)/total number of weekly platelet counts (N1).
Negative result at the patient’s last time point tested.
Patients who had additional positive tests for transient anti-romiplostim antibodies: patient 13 at week 76; patient 19 at weeks 18 and 21; and patient 24 at weeks 104, 145, 167, 180, and 194.
Patient 19 experienced additional AEs of bleeding (contusion) and hypersensitivity (drug eruption and rash) at week 18 and bleeding (blood urine, contusion, petechiae) and hypersensitivity (drug eruption, rash) at week 21.
Positive result at the patient’s last time point tested.
Patients who had additional positive tests for persistent anti-romiplostim antibodies: patient 12 at week 100; patient 25 at weeks 101, 124, 148, and 157.