Caplacizumab in pediatric immune thrombotic thrombocytopenic purpura: the UK TTP Registry experience.

Pediatric thrombotic thrombocytopenic purpura (TTP) is an ultrarare disease. Immune TTP (iTTP) is driven by anti-ADAMTS13 autoantibodies causing an imbalanced von Willebrand factor (VWF):ADAMTS13 axis, and rarer still in children, but potentially life-threatening. Caplacizumab is licensed for iTTP treatment in adults and adolescents aged ≥12 years who weigh ≥40 kg. There is a need to clarify whether caplacizumab can be used in younger children. We retrospectively described caplacizumab use in 16 patients under 18 years of age from the UK TTP Registry, including 4 children aged <12 years. For patients weighing <40 kg (n = 3), caplacizumab was dosed at 5 mg once dailyThe youngest patient was 33 months old at diagnosis. Plasma exchange (PEX) was used in 15 patients, with a median of 5 exchanges required before platelet count normalization (range, 2-9). One patient was managed without PEX. All patients achieved normalization of platelet count (median, 5.5 days; range, 3-28) and ADAMTS13 activity (median, 35 days; range, 8-149), with a median hospital admission of 11 days (range, 5-26). There were no refractory patients. One patient relapsed 9 months after presentation. Bleeding requiring VWF supplementation and reduction of caplacizumab use occurred in 1 patient with severe epistaxis, with no significant intracranial or gastrointestinal bleeding. We demonstrated the efficacy and safety of caplacizumab in the pediatric population, which is synonymous with the adult trial data: primarily, reduction of PEX compared with the precaplacizumab era. This has implications for the intensification and duration of admission, particularly relevant in pediatric care.

Taylor A ，Keogh L ，Dickens E ，Dutt T ，Grainger J ，Gregory R ，Mapplebeck C ，Richards M ，Stokley S ，Salta S ，Taylor T ，Scully M ... -  《-》

Real-world experience with caplacizumab in the management of acute TTP.

The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti-von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.

Dutt T ，Shaw RJ ，Stubbs M ，Yong J ，Bailiff B ，Cranfield T ，Crowley MP ，Desborough M ，Eyre TA ，Gooding R ，Grainger J ，Hanley J ，Haughton J ，Hermans J ，Hill Q ，Humphrey L ，Lowe G ，Lyall H ，Mohsin M ，Nicolson PLR ，Priddee N ，Rampotas A ，Rayment R ，Rhodes S ，Taylor A ，Thomas W ，Tomkins O ，Van Veen JJ ，Lane S ，Toh CH ，Scully M ... -  《-》

Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura.

Scully M ，Cataland SR ，Peyvandi F ，Coppo P ，Knöbl P ，Kremer Hovinga JA ，Metjian A ，de la Rubia J ，Pavenski K ，Callewaert F ，Biswas D ，De Winter H ，Zeldin RK ，HERCULES Investigators ... -  《-》

ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy.

Mingot-Castellano ME ，García-Candel F ，Martínez-Nieto J ，García-Arroba J ，de la Rubia-Comos J ，Gómez-Seguí I ，Paciello-Coronel ML ，Valcárcel-Ferreiras D ，Jiménez M ，Cid J ，Lozano M ，García-Gala JM ，Angós-Vazquez S ，Vara-Pampliega M ，Guerra-Domínguez L ，Ávila-Idrobo LF ，Oliva-Hernandez A ，Zalba-Marcos S ，Tallón-Ruiz I ，Ortega-Sánchez S ，Goterris-Viciedo R ，Moreno-Jiménez G ，Domínguez-Acosta L ，Araiz-Ramírez M ，Hernández-Mateos L ，Flores-Ballesteros E ，Del Río-Garma J ，Pascual-Izquierdo C ... -  《-》

Refining the standard of care in immune thrombotic thrombocytopenic purpura.

Laurence J 《-》