HERCULES

Clinical question

Does adding caplacizumab, an anti-von Willebrand factor nanobody, to plasma exchange speed recovery and reduce TTP-related complications in acquired TTP?

What the trial found

Among patients with acquired TTP, caplacizumab led to faster normalization of the platelet count (2.69 vs 2.88 days). The composite of TTP-related death, recurrence or a thromboembolic event during treatment was 12% with caplacizumab vs 49% with placebo, recurrence at any time was 12% vs 38%, and no caplacizumab-treated patient developed refractory disease vs three on placebo. Patients on caplacizumab needed less plasma exchange and a shorter hospital stay. Mucocutaneous bleeding was more common (65% vs 48%).

Clinical interpretation

HERCULES made caplacizumab an add-on to plasma exchange and immunosuppression that protects against early exacerbation and ischemic events while the underlying autoimmune ADAMTS13 deficiency is treated. It does not replace plasma exchange or immunosuppression, and the bleeding signal needs monitoring.

Limitations

• Mucocutaneous bleeding was more frequent with caplacizumab (65% vs 48%).
• Caplacizumab does not treat the autoimmune ADAMTS13 deficiency itself, so immunosuppression and ADAMTS13 monitoring remain necessary.