Table 2.
Serious non-bleeding toxicities in trials of romiplostim and eltrombopag.
| Toxicity | Romiplostim | Eltrombopag | ||||
|---|---|---|---|---|---|---|
| Placebo-controlled trialsa | Extension study (n = 291) | Placebo-controlled trialsb | Extension study (n = 299) | |||
| Romplostim (n = 100) | Placebo (n = 46) | Eltrombopag (n = 314) | Placebo (n = 137) | |||
| n (%) | n (%) | n (%) | n (%) | n (%) | n (%) | |
| TGF class-specific toxicities | ||||||
| Bone marrow fibrosis | 1 (1)c | 0c | 9 (3)c | 0c | 0c | 8 (3)d |
| Thrombosis | 2 (2) | 2 (4) | 17 (6) | 1 (0.3) | 0 | 13 (4) |
| Rebound thrombocytopenia | 13 (13) | NR | NR | 20 (6) | 10 (7) | 14 (5)e |
| Hematologic malignancy | 0 | 0 | 1 (0.3) | 0 | 0 | 1 (0.3) |
| Romiplostim-specific toxicities | ||||||
| Neutralizing antibody formation | 0 | 0 | 2f | NA | NA | NA |
| Eltrombopag-specific toxicities | ||||||
| Hepatotoxicityg | 0 | 0 | NR | 33 (11) | 9 (7) | 24 (8) |
| Cataract formation/progression | NA | NA | NA | 5 (2) | 2 (1) | NR |
Includes a pooled analysis of the 6-week phase II trial and the 24-week phase III trials of romiplostim.
Includes a pooled analysis of the 6-week phase II trials and the 6-week and 6-month phase III trials of eltrombopag.
Routine bone marrow biopsies were not performed. Therefore, the number of identified cases may underestimate the true incidence of bone marrow fibrosis.
Bone marrow biopsy, mandated after 12 months of therapy, has been performed in 86 patients.
168 patients had a dose interruption or drug discontinuation.
Two patients developed neutralizing anti-romiplostim antibodies. These antibodies did not cross-react with endogenous thrombopoietin.
Defined as ALT ≥3x ULN, AST ≥3x ULN, alkaline phosphatase >1.5x ULN, total bilirubin >1.5x ULN.