Long‐term follow‐up of patients treated with caplacizumab and safety and efficacy of repeat caplacizumab use: Post‐HERCULES study

INTRODUCTION: Caplacizumab demonstrated efficacy and safety in patients with immune‐mediated thrombotic thrombocytopenic purpura (iTTP) in the phase 3 HERCULES trial. However, data on long‐term outcomes following caplacizumab treatment are limited. OBJECTIVES: The post‐HERCULES trial (NCT02878603) evaluated long‐term outcomes of patients with iTTP treated with caplacizumab in HERCULES and safety and efficacy of repeated caplacizumab use. PATIENTS/METHODS: Over 3 years of follow‐up, patients could receive open‐label caplacizumab with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of recurrence. Adverse events (AEs) were assessed during the overall study period (intention‐to‐observe [ITO] population) and during recurrences (recurrence population). TTP‐related events (TTP‐related death, recurrence, major thromboembolic events) were assessed in the efficacy ITO population (patients without recurrence during HERCULES or before post‐HERCULES). RESULTS: Among 104 enrolled patients, incidences of AEs and serious AEs were similar between patients who had received caplacizumab + TPE + IST during HERCULES (n = 75) and those treated with placebo + TPE + IST (placebo; n = 29). TTP‐related events occurred in 8% of patients (4/49) randomized to caplacizumab during HERCULES versus 38% (11/29) randomized to placebo. Nineteen patients had ≥1 recurrence; 13 of these were treated with caplacizumab. The first recurrence episode was resolved or resolving for all patients treated with caplacizumab, including nine patients with repeat caplacizumab use. All second recurrences (6/6) were resolved. Safety profile of caplacizumab for treatment of recurrence was consistent with HERCULES; most bleeding events were nonserious. No major cases of organ dysfunction were observed. CONCLUSIONS: Long‐term follow‐up supports the safety and efficacy of caplacizumab for iTTP and its repeated use for recurrences.