Is Caplacizumab Effective in All Patients with iTTP?

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening condition characterized by microvascular thrombosis due to ADAMTS13 deficiency. Standard treatment includes therapeutic plasma exchange (TPE) and immunosuppression, but outcomes remain suboptimal. Caplacizumab, a nanobody that inhibits von Willebrand factor–platelet interaction, demonstrated benefit in the phase 3, randomized HERCULES trial, in which 145 patients with acute iTTP received caplacizumab or placebo alongside standard therapy with steroids with or without rituximab (NEJM JW Oncol Hematol Jan 17 2019 and N Engl J Med 2019; 380:335).

Now, in a post hoc analysis, researchers evaluated the efficacy and safety of caplacizumab across clinically relevant subgroups: prior iTTP history (de novo vs. recurrent), disease severity at presentation, and initial immunosuppression regimen. The composite efficacy outcome was iTTP-related death, exacerbation, or major thromboembolic events.

Among the findings:

• Caplacizumab demonstrated improved efficacy across all subgroups, with faster platelet count response and fewer composite outcomes compared with placebo.
• In patients with de novo and in those with recurrent iTTP, caplacizumab reduced time to platelet count response by approximately 0.2 to 0.3 days compared with placebo (P≤0.05).
• Among patients treated with corticosteroids plus rituximab, exacerbations occurred in none who received caplacizumab versus 50% who received placebo.
• Compared with placebo, caplacizumab was associated with more-frequent mucocutaneous bleeding events across all subgroups.
• ADAMTS13 recovery time was faster with caplacizumab combined with corticosteroids plus rituximab than with either caplacizumab or placebo combined with corticosteroids alone.