Effectiveness of Adjunctive Caplacizumab Treatment in Immune Thrombotic Thrombocytopenic Purpura in Real-Life Setting. Retrospective Monocentric Cohort
Authors: Markovic Uros , Frazzetto Sara , Grasso Stephanie , Giunta Giuliana , Sapuppo Gabriele , Duminuco Andrea , Calagna Marianna , Esposito Benedetta , Fazio Manlio , Nardo Antonella , Gullo Lara , Santuccio Gabriella , Sorbello Chiara Maria Catena , Leotta Dario , Di Raimondo Francesco , Giuffrida Gaetano 
Published: December 2024

Introduction. Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disease caused by a severe deficiency of the metalloproteinase ADAMTS13, that results in platelet-rich thrombi in the microvessels, with subsequent red cells fragmentation and end-organ damage, predominantly affecting the brain, heart, kidneys and intestine. The standard of care (SOC) relies on plasma exchange (PEX) and immunosuppressants, while caplacizumab (CAPLA), a bivalent anti-von Willebrand (vWF) nanobody, was introduced recently in clinical practice.
Methods. We retrospectively analyzed data from 81 patients who were diagnosed with iTTP at our center and experienced a total of 165 acute clinical episodes that required standard treatment between 1990 and 2024, to assess the effectiveness of clinical response. We evaluated each acute episode, in terms of the number of PEX sessions required to obtain platelet normalization, number of days of hospitalization in in-patient setting, and the early relapse rate based on the use of CAPLA. Mann-Whitney test was used for evaluation of statistical significance of continuous variables. Caplacizumab was used starting from the onset of acute episode until 30 days after the PEX suspension as per national treatment approval.
Results. The median age at first episode was 39.9 years (range 13-75) and was prevalently diagnosed in female patients (63%). The patients presented with median platelets count of 14x109/L, a median plasmic score of 6, a median ADAMTS13 level &lt;1% (range 0-10), and a median ADAMTS13-inhibitor of 49 U/mL (range 2-111) (available in 40% of patients). After a median follow-up of 6.4 years, 47 patients (58%) suffered from at least one clinical relapse (range 1-7) and all episodes were treated with PEX and corticosteroids.
A total of 165 acute episodes were analyzed with according to caplacizumab administration, indentifying 39 cases (25.5%) treated with CAPLA, while 126 cases were treated with SOC (74.5%), due to lack of availability. Baseline parameters between the two cohorts were comparable. The median number of PEX required before confirmed platelet count normalization for two consecutive days was 6 for CAPLA group and was significantly lower than SOC group (median 9.5 PEX sessions, p&lt;0.0001), as well as days of hospitalization, that were 8 and 13.5, respectively (p&lt;0.0001). Out of 11 patients with early relapse following 30 days from PEX suspension, the rates were 13% and 5% respectively in CAPLA and SOC groups, that were associated with higher median inhibitor levels (66 U/mL). Rituximab was used in 13% of CAPLA compared to 9.5% of SOC patients due to lack of response as second line treatment, while additional four and two patients each from the early relapse group used rituximab after the re-occurrence of thrombocytopenia, respectively 10% and 1% for CAPLA and SOC.
Conclusions. Here, we reported a comparative analysis of iTTP episodes treated with and without caplacizumab at our center. The data presented suggest that caplacizumab reduces significantly the treatment burden of iTTP episodes in terms of the number of PEX procedures and days of hospitalization, confirming faster clinical response and shorter access in in-patient setting of CAPLA group. Caplacizumab treatment, on the other hand, could potentially lead to higher rates of early relapse due to premature PEX suspension and more frequent use of rituximab, although more studies are needed.