https://orcid.org/0000-0002-5990-0279
Key Point
Caplacizumab with immunosuppression, but without additional TPE, is an effective and safe treatment strategy for acute iTTP.
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening autoimmune disorder caused by a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency. Caplacizumab, an anti–von Willebrand factor nanobody, is approved for iTTP treatment, reducing the need for therapeutic plasma exchange (TPE) and improving platelet count recovery and survival. We conducted a retrospective study on 42 acute iTTP cases in Austria and Germany, treated with a modified regimen aimed at avoiding TPE if platelet count increased after the first caplacizumab dose. Baseline characteristics and patient outcomes were compared with a control group of 59 patients with iTTP receiving frontline treatment with TPE, caplacizumab, and immunosuppression. The main outcome was the time to platelet count normalization. Secondary outcomes included clinical response, exacerbation, refractory iTTP, iTTP-related deaths, and the time to platelet count doubling. The median time to platelet count normalization was similar between the 2 cohorts (3 and 4 days; P = .31). There were no significant differences in clinical response, exacerbations, refractoriness, iTTP-related deaths, or time to platelet count doubling, reflecting the short-term treatment response. Four patients did not respond to the first caplacizumab dose, and TPE was subsequently initiated. Cytomegalovirus infection, HIV/hepatitis B virus coinfection, an ovarian teratoma with associated antiplatelet antibodies, and multiple platelet transfusions before the correct diagnosis may have impeded the immediate treatment response in these patients. In conclusion, caplacizumab and immunosuppression alone, without TPE, rapidly controlled thrombotic microangiopathy and achieved a sustained clinical response in iTTP. Our study provides a basis for TPE-free iTTP management in experienced centers via shared decision-making between patients and treating physicians.
Comments
Potential inclusion of milder iTTP cases in the TPE-Free Cohort
The TPE-free cohort included patients with immediate platelet recovery after the first caplacizumab dose and stable clinical conditions. Additionally, lactate dehydrogenase levels at onset and ICU admission rates were significantly lower in the TPE-free cohort, suggesting the cohort may include milder cases.
Furthermore, the levels of ADAMTS13 inhibitor or anti-ADAMTS13 IgG either at onset or during the treatment course were unclear. As the persistence of ADAMTS13 inhibitor may lead to delayed recovery of ADAMTS13 activity1, ADAMTS13 inhibitor levels should be measured during the disease course. Additionally, based on the residual ADAMTS13 inhibitor levels, antibody removal through TPE or further immunosuppression may be required for the early recovery of ADAMTS13 activity, which may help prevent the prolonged use of caplacizumab.
1Saito K et al (2024) Blood Adv, 8, 2151-2159
Conflict-of-interest disclosure
K.Sakai received lecture fees from Sanofi. M.M. provided consultancy services for Takeda, Alexion Pharma, and Sanofi; received speaker fees for Takeda, Alexion Pharma, Asahi Kasei Pharma, and Sanofi; and received research funding from Alexion Pharma, Chugai Pharmaceutical, Asahi Kasei Pharma, and Sanofi. K.Saito declares no competing financial interests.