Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data

Abstract

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1–43) from initial diagnosis for 32 (6–47) dosages. In the caplacizumab group, a median of 12 (8–23) patients required plasma exchange sessions versus 14 (6–32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6–320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p < 0.001). Overall, caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange, re-administration, and cases without previous plasma exchange treatment. No major hemorrhagic events were observed. Cessation of dosing guided by ADAMTS13 has ensured a low relapse rate.

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside

“…Initial treatment with human FVIII should be limited only to cases when access to the above three agents is not available and in patients with low-titer inhibitors (<5 BU) [87]. Plasma-deprived FVIIa/FX has been also evaluated in patients with AHA, with favorable outcomes without an increase in the thrombotic risk [103]. Emicizumab, a monoclonal antibody restoring the function of missing FVIII by connecting FIXa and FX, has been used off-label in AHA [104][105][106][107][108].…”

“…In a recently published retrospective study, 80 participants who received corticosteroids combined with rituximab IST had a 93.3% complete remission rate [ 101 ]. Rituximab has been used as an immunosuppressant in various benign and malignant hematological disorders [ 102 , 103 , 104 ] as cytotoxic agents’ cyclophosphamide (PO, 1.5–2 mg/kg/day, for a maximum of 6 weeks) or mycophenolate mofetil (1 g/day for 1 week, and after 2 g/day). In a randomized controlled study comparing corticosteroids plus rituximab with corticosteroids plus cyclophosphamide in patients with AHA, similar efficacy and safety were reported between the two drug combinations [ 105 ].…”