Scully, MarieMarieScullyde la Rubia, JavierJavierde la RubiaPavenski, KaterinaKaterinaPavenskiMetjian, AraAraMetjianKnöbl, PaulPaulKnöblPeyvandi, FloraFloraPeyvandiCataland, SperoSperoCatalandCoppo, PaulPaulCoppoKremer Hovinga Strebel, Johanna AnnaJohanna AnnaKremer Hovinga Strebel0000-0002-1300-7135Minkue Mi Edou, JessicaJessicaMinkue Mi EdouDe Passos Sousa, RuiRuiDe Passos SousaCallewaert, FilipFilipCallewaertGunawardena, SriyaSriyaGunawardenaLin, JulieJulieLin2024-10-112024-10-112022-12https://boris-portal.unibe.ch/handle/20.500.12422/87709INTRODUCTION 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' 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. First recurrence episode was resolved or resolving for all patients treated with caplacizumab, including 9 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 non-serious. 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.enBlood platelets caplacizumab follow-up studies thrombotic thrombocytopenic purpura von Willebrand factor600 - Technology::610 - Medicine & health300 - Social sciences, sociology & anthropology::340 - Lawarticle10.48350/1732493613851710.1111/jth.15892