a retrospective, observational study on the response to caplacizumab treatment in attp patients: the italian experience (roscapli)

Conditions: Thrombotic Thrombocytopenic Purpura

Summary: thrombotic thrombocytopenic purpura (ttp) is a rare disease with a mortality rate of over 90% if left untreated \[1\]. ttp is a prototype of the thrombotic microangiopathies (tmas), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic hemolytic anemia (maha), thrombocytopenia, and potential end-organ injury mainly involving the brain, heart, and kidneys leading to significant morbidity/mortality

thrombotic thrombocytopenic purpura (ttp) is a rare disease with a mortality rate of over 90% if left untreated \[1\]. ttp is a prototype of the thrombotic microangiopathies (tmas), and it is characterized by disseminated formation of platelet-rich thrombi in arterioles and capillaries resulting in microangiopathic hemolytic anemia (maha), thrombocytopenia, and potential end-organ injury mainly involving the brain, heart, and kidneys leading to significant morbidity/mortality. ttp can either be hereditary or acquired, and the pathogenesis of the latter consists of autoimmune antibodies against the metalloproteinase "a disintegrin and metalloproteinase with a thrombospondin type 1 motif (adamts13)", and adamts13 is responsible for the cleavage of ultra-large multimers of von willebrand factor (vwf), which induces activation of platelets through glycoprotein ib-alpha (gpib-α) receptors and the activated a1 domain of the vwf multimers without a trigger-like endothelial damage or tissue factor. acquired ttp (attp) can be primary (idiopathic) or secondary to some underlying disorders. therapeutic plasma exchange (pex) is the mainstay of treatment of attp, and with the introduction of pex, the mortality rate declined dramatically below 20% \[1\]. the rationale of pex is the replacement of adamts13, and removal of ultra-large vwf and anti adamts13 antibodies. in newly diagnosed patients with attp, pex and corticosteroids are usually started upfront together \[3\]. however, a subset of patients may remain refractory to this treatment or have an initial response but relapse after the discontinuation of pex during the follow-up. there is limited information or consensus available on the management of relapsed/refractory attp. while managing pex refractory patients, pex may be intensified to 1.5 plasma volume (pv), and even twice daily pex can be used \[4\]. in patients remaining refractory to pex plus corticosteroids, the administration of high-dose methylprednisolone 1 g per day for 3 days can be the choice of treatment \[5\].other treatment options in patients with relapsed/refractory ttp may include rituximab, vincristine, cyclophosphamide, cyclosporine a, and splenectomy\[6-8\]. caplacizumab is fully reimbursed by the national health system in italy since january 2020. while observational data have recently been published in other countries, such as germany, on the efficacy and safety of caplacizumab \[18\], cumulative data deriving from the italian centers that manage the therapy of ttp with caplacizumab have not yet been collected. the aim of this proposal is, therefore,to collect retrospective observationaldata on the response to caplacizumab treatment in patients with attp treated with this drug in italy during the q4-2019 and q1-2021.

Eligibility criteria:
inclusion criteria: * the patients included in this study should have received caplacizumab for treatment in the period between q4-2019 and the end of february 2021 while the end of follow up observation is scheduled for q1-2021 (to observe at least one month of post treatment follow up). * the diagnosis should be based on either clinical/laboratory parameters inclusive of measurement of adamts13 level \ 5) already computed or retrospectively calculated as previously detailed \[19\] for centers that did not measure the adamts13 level. exclusion criteria: * patients treated with uncertain attp diagnosis according to the above inclusion criteria - patients manifesting clinical signs like attp but characterized by a different pathogenesis (e.g. cancer, sepsis)