The UK real-world evidence of caplacizumab in iTTP represents the largest, international data collection outside clinical trials to date.
The UK real-world evidence of caplacizumab is comparable with RCT outcomes and includes paediatric patients.
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, trialled in two multicentre, randomised-placebo-controlled trials leading to EU and FDA approval, has been available in the UK through a patient-access scheme. Data was collected retrospectively from 2018-2020 for 85 patients receiving caplacizumab, including 4 children, from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial endpoints and historical outcomes in the pre-caplacizumab era. 84/85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalisation (3 days), duration of PEX (7 days) and hospital stay (12 days) was comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalisation was favourable compared with historical outcomes (p<0.05). TTP recurrence occurred in 5/85 patients; all with persistent ADAMTS13 activity <5iu/dL. Of 31 adverse events in 26 patients, 17/31 (55%) were bleeding episodes and 5/31 (16%) were thrombotic events (two unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4/5 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 receiving caplacizumab outside clinical trials, including paediatric patients. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.