Targeted therapies for iTTP: risks, benefits, and unknowns
| Drug . | Risks . | Benefits . | Unknowns . |
|---|---|---|---|
| Rituximab (cost, ∼$20 000 per 4-dose course) | Infusion reactions (first dose: 12%-77%, mostly mild-moderate; decreases with subsequent infusions) | Likely increases relapse-free survival | Consequences of immunosuppression especially with retreatment |
| HBV reactivation (2%) | Upfront for acute iTTP (10% vs 57% at 5 y) | Risk of progressive multifocal leukoencephalopathy (never reported in iTTP) | |
| Preemptively for ADAMTS13 deficiency in remission (15% vs 74%) | |||
| Caplacizumab (cost, ∼$270 000 for a 4-wk course) | Mucosal bleeding (65%, mostly mild to moderate) | Reduction in mortality (0% vs 4%) | Real-world safety/efficacy outside of expert centers |
| Reduction in refractoriness (0% vs 4%) | Effect of cost on utilization | ||
| Reduction in median hospital days (9 vs 12 d) | Adherence in nonclinical trial | ||
| Reduction in PEX days (5 vs 7 d) | Optimal duration of therapy | ||
| (all vs placebo) | |||
| Bortezomib (cost, ∼$5200 for 4 doses) | Thrombocytopenia (16%-52%) | Targets plasma cells | Identifying patients likely to benefit |
| Drug-induced TMA (rare) | Extensive experience with drug (from use in plasma cell dyscrasias) | Durability of response | |
| Peripheral neuropathy (37% with subcutaneous dosing) | Optimal delivery and schedule | ||
| Varicella zoster reactivation (6%-11%) | Utility of combining with other immunosuppressive agents | ||
| Recombinant ADAMTS13 (cost unknown) | None reported | Raises ADAMTS13 activity in congenital TTP | Currently no evidence on use in iTTP |
| Drug . | Risks . | Benefits . | Unknowns . |
|---|---|---|---|
| Rituximab (cost, ∼$20 000 per 4-dose course) | Infusion reactions (first dose: 12%-77%, mostly mild-moderate; decreases with subsequent infusions) | Likely increases relapse-free survival | Consequences of immunosuppression especially with retreatment |
| HBV reactivation (2%) | Upfront for acute iTTP (10% vs 57% at 5 y) | Risk of progressive multifocal leukoencephalopathy (never reported in iTTP) | |
| Preemptively for ADAMTS13 deficiency in remission (15% vs 74%) | |||
| Caplacizumab (cost, ∼$270 000 for a 4-wk course) | Mucosal bleeding (65%, mostly mild to moderate) | Reduction in mortality (0% vs 4%) | Real-world safety/efficacy outside of expert centers |
| Reduction in refractoriness (0% vs 4%) | Effect of cost on utilization | ||
| Reduction in median hospital days (9 vs 12 d) | Adherence in nonclinical trial | ||
| Reduction in PEX days (5 vs 7 d) | Optimal duration of therapy | ||
| (all vs placebo) | |||
| Bortezomib (cost, ∼$5200 for 4 doses) | Thrombocytopenia (16%-52%) | Targets plasma cells | Identifying patients likely to benefit |
| Drug-induced TMA (rare) | Extensive experience with drug (from use in plasma cell dyscrasias) | Durability of response | |
| Peripheral neuropathy (37% with subcutaneous dosing) | Optimal delivery and schedule | ||
| Varicella zoster reactivation (6%-11%) | Utility of combining with other immunosuppressive agents | ||
| Recombinant ADAMTS13 (cost unknown) | None reported | Raises ADAMTS13 activity in congenital TTP | Currently no evidence on use in iTTP |
HBV, hepatitis B virus; TMA, thrombotic microangiopathy.