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 ... -  《-》

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 ... -  《-》

Caplacizumab for Acquired Thrombotic Thrombocytopenic Purpura.

Peyvandi F ，Scully M ，Kremer Hovinga JA ，Cataland S ，Knöbl P ，Wu H ，Artoni A ，Westwood JP ，Mansouri Taleghani M ，Jilma B ，Callewaert F ，Ulrichts H ，Duby C ，Tersago D ，TITAN Investigators ... -  《-》

Caplacizumab: an anti-von Willebrand factor antibody for the treatment of thrombotic thrombocytopenic purpura.

The pharmacology, pharmacokinetics, efficacy, safety, dosing and administration, and place in therapy of caplacizumab, a novel antibody fragment that inhibits von Willebrand factor, for the treatment of acquired thrombotic thrombocytopenic purpura (TTP) are summarized. Caplacizumab is a humanized anti-von Willebrand factor monoclonal antibody fragment that inhibits the interaction between ultralarge von Willebrand factor multimers and platelets. Caplacizumab is indicated for use in combination with standard-of-care modalities such as plasma exchange and immunosuppressive therapy for the treatment of adults with acquired TTP. By inhibiting von Willebrand factor, caplacizumab offers a new approach to the management of TTP by preventing the development of potentially life-threatening microvascular thrombosis that can occur in the disease process. In a randomized, placebo-controlled phase 3 trial, patients with acquired TTP treated with caplacizumab had more rapid platelet level normalization than placebo users; caplacizumab use also resulted in lower rates of disease recurrence and TTP-related death. The most common adverse events associated with caplacizumab use are bleeding-related events. In a phase 3 trial, serious bleeding-related adverse events were reported in 8 patients (11%) in the caplacizumab group and 1 patient (1%) in the placebo group. Caplacizumab is administered as an 11-mg intravenous loading dose 15 minutes prior to plasma exchange, followed by administration of 11 mg subcutaneously daily after plasma exchange. Once-daily caplacizumab administration can be continued for 30 days after the last plasma exchange. The medication and supplies for administration are provided as a single-use kit; patients should be trained on proper reconstitution and self-administration technique prior to the use of caplacizumab in the ambulatory setting. Caplacizumab is a first-in-class von Willebrand factor inhibitor approved for the treatment of adults with acquired TTP.

Hollifield AL ，Arnall JR ，Moore DC 《-》