TY - JOUR
T1 - Caplacizumab use in immune-mediated thrombotic thrombocytopenic purpura
T2 - an international multicentre retrospective Cohort study (The Capla 1000+ project)
AU - Coppo, Paul
AU - Bubenheim, Michael
AU - Benhamou, Ygal
AU - Völker, Linus
AU - Brinkkötter, Paul
AU - Kühne, Lucas
AU - Knöbl, Paul
AU - Mingot-Castellano, Maria Eva
AU - Pascual-Izquierdo, Cristina
AU - de la Rubia, Javier
AU - Del Rio Garma, Julio
AU - Chaturvedi, Shruti
AU - Masias, Camila
AU - Mazepa, Marshall
AU - Zheng, X Long
AU - Sinkovits, György
AU - Réti, Marienn
AU - Patriquin, Christopher J
AU - Pavenski, Katerina
AU - Boechat, Tiago
AU - Farias, João
AU - Oliveira Ribeiro, Eduardo Flavio
AU - Lobo de Andrade, Michaela Larissa
AU - Veyradier, Agnès
AU - Joly, Bérangère
AU - Bouzid, Raïda
AU - Sakai, Kazuya
AU - Matsumoto, Masanori
AU - Agosti, Pasquale
AU - Mancini, Ilaria
AU - Peyvandi, Flora
AU - Gavriilaki, Eleni
AU - Stubbs, Matthew
AU - Hmaid, Amjad
AU - Cataland, Spero
AU - Lämmle, Bernhard
AU - Scully, Marie
N1 - © 2025 The Author(s).
PY - 2025/4
Y1 - 2025/4
N2 - BACKGROUND: The anti-Von Willebrand Factor (VWF) nanobody caplacizumab is licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in association with therapeutic plasma exchange (TPE) and immunosuppression. However, whether caplacizumab reduces mortality, and its optimal timing of initiation, is not completely settled.METHODS: This international, multicenter retrospective cohort study recruited patients from 2018 until 2023 and data collection took place from January 1st to June 30th 2023 in the participating centers. One thousand and fifteen patients were treated with daily TPE, immunosuppression with corticosteroids ± rituximab, and caplacizumab (caplacizumab group), which was compared to historic controls treated with TPE and corticosteroids ± rituximab (control group, N = 510). Caplacizumab initiation was classified as early (within 3 days; 76% of cases) or delayed (≥4 days from first TPE).FINDINGS: Three-month survival rate in the caplacizumab group was 98.5%, compared with 94% in controls (P < 0.0001). Three-month mortality rate was 4.2-fold higher in controls than in caplacizumab-treated patients (95% CI: 2.22-7.7, P < 0.0001), regardless of rituximab use. In both groups, death was observed primarily in elderly patients, and age was the factor most associated with 3-month mortality. Patients receiving caplacizumab showed reduced refractoriness, exacerbations, and required fewer TPE sessions to achieve clinical response versus controls (P < 0.0001 all). Time to clinical response in the caplacizumab group was shorter than in controls, and even shorter in patients with early caplacizumab initiation (P < 0.0001 both). Caplacizumab-related adverse events were observed in 21% of patients, with major bleeding in 2.4%, which was more common in elderly patients.INTERPRETATION: The early association of Caplacizumab to TPE and immunosuppression significantly reduces unfavorable outcomes during iTTP, including death, and alleviates the burden of care at the potential expense of bleeding events. Advanced age, however, remains an adverse factor for survival. The limitations of our study include its retrospective and multicentric design and the use of a historical control cohort.FUNDING: None.
AB - BACKGROUND: The anti-Von Willebrand Factor (VWF) nanobody caplacizumab is licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) in association with therapeutic plasma exchange (TPE) and immunosuppression. However, whether caplacizumab reduces mortality, and its optimal timing of initiation, is not completely settled.METHODS: This international, multicenter retrospective cohort study recruited patients from 2018 until 2023 and data collection took place from January 1st to June 30th 2023 in the participating centers. One thousand and fifteen patients were treated with daily TPE, immunosuppression with corticosteroids ± rituximab, and caplacizumab (caplacizumab group), which was compared to historic controls treated with TPE and corticosteroids ± rituximab (control group, N = 510). Caplacizumab initiation was classified as early (within 3 days; 76% of cases) or delayed (≥4 days from first TPE).FINDINGS: Three-month survival rate in the caplacizumab group was 98.5%, compared with 94% in controls (P < 0.0001). Three-month mortality rate was 4.2-fold higher in controls than in caplacizumab-treated patients (95% CI: 2.22-7.7, P < 0.0001), regardless of rituximab use. In both groups, death was observed primarily in elderly patients, and age was the factor most associated with 3-month mortality. Patients receiving caplacizumab showed reduced refractoriness, exacerbations, and required fewer TPE sessions to achieve clinical response versus controls (P < 0.0001 all). Time to clinical response in the caplacizumab group was shorter than in controls, and even shorter in patients with early caplacizumab initiation (P < 0.0001 both). Caplacizumab-related adverse events were observed in 21% of patients, with major bleeding in 2.4%, which was more common in elderly patients.INTERPRETATION: The early association of Caplacizumab to TPE and immunosuppression significantly reduces unfavorable outcomes during iTTP, including death, and alleviates the burden of care at the potential expense of bleeding events. Advanced age, however, remains an adverse factor for survival. The limitations of our study include its retrospective and multicentric design and the use of a historical control cohort.FUNDING: None.
U2 - 10.1016/j.eclinm.2025.103168
DO - 10.1016/j.eclinm.2025.103168
M3 - Article
C2 - 40235949
SN - 2589-5370
VL - 82
SP - 103168
JO - eClinicalMedicine
JF - eClinicalMedicine
ER -