Pros and cons of ITI vs emicizumab without ITI
| . | Pros . | Cons . |
|---|---|---|
| Mortality | Patients with inhibitors have increased mortality. | Data regarding mortality predate the licensure of emicizumab and may not apply with emicizumab available. |
| Breakthrough bleeding treatment | Treatment of breakthrough bleeding is much simpler, safer, and less costly with factor replacement than with bypassing agents. | Breakthrough bleeding is infrequent with emicizumab. Mitigation strategies have demonstrated the ability to treat breakthrough bleeds safely. |
| Unforeseen adverse events | Emicizumab is a novel agent, and only ∼400 patients have ever received it. It is always possible that unforeseen adverse events could occur. Treatment with factor replacement is known to be very safe (with the exception of inhibitor formation). | The mechanism of action of substituting for FVIIIa suggests nonthrombotic-type events should not occur or be rare. Monoclonal antibodies have been in widespread use for several decades, and unforeseen side effects are uncommon. |
| Gene therapy | Gene therapy when it becomes available may not be effective in patients with active inhibitors but could be effective in patients who have been tolerized. | Some animal data suggest that gene therapy could lead to tolerization when active inhibitors are present. |
| . | Pros . | Cons . |
|---|---|---|
| Mortality | Patients with inhibitors have increased mortality. | Data regarding mortality predate the licensure of emicizumab and may not apply with emicizumab available. |
| Breakthrough bleeding treatment | Treatment of breakthrough bleeding is much simpler, safer, and less costly with factor replacement than with bypassing agents. | Breakthrough bleeding is infrequent with emicizumab. Mitigation strategies have demonstrated the ability to treat breakthrough bleeds safely. |
| Unforeseen adverse events | Emicizumab is a novel agent, and only ∼400 patients have ever received it. It is always possible that unforeseen adverse events could occur. Treatment with factor replacement is known to be very safe (with the exception of inhibitor formation). | The mechanism of action of substituting for FVIIIa suggests nonthrombotic-type events should not occur or be rare. Monoclonal antibodies have been in widespread use for several decades, and unforeseen side effects are uncommon. |
| Gene therapy | Gene therapy when it becomes available may not be effective in patients with active inhibitors but could be effective in patients who have been tolerized. | Some animal data suggest that gene therapy could lead to tolerization when active inhibitors are present. |