Management of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchange.

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.

Kühne L ，Knöbl P ，Eller K ，Thaler J ，Sperr WR ，Gleixner K ，Osterholt T ，Kaufeld J ，Menne J ，Buxhofer-Ausch V ，Mühlfeld A ，Seelow E ，Schreiber A ，Todorova P ，Cukoski S ，Jabs WJ ，Özcan F ，Gäckler A ，Schönfelder K ，Seibert FS ，Westhoff T ，Schwenger V ，Eichenauer DA ，Völker LA ，Brinkkoetter PT ... -  《-》

A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP.

The anti-von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

Coppo P ，Bubenheim M ，Azoulay E ，Galicier L ，Malot S ，Bigé N ，Poullin P ，Provôt F ，Martis N ，Presne C ，Moranne O ，Benainous R ，Dossier A ，Seguin A ，Hié M ，Wynckel A ，Delmas Y ，Augusto JF ，Perez P ，Rieu V ，Barbet C ，Lhote F ，Ulrich M ，Rumpler AC ，de Witte S ，Krummel T ，Veyradier A ，Benhamou Y ... -  《-》

Persistent ADAMTS13 inhibitor delays recovery of ADAMTS13 activity in caplacizumab-treated Japanese patients with iTTP.

For patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), caplacizumab, a nanobody against von Willebrand factor A1 domain, has become crucial. Delayed normalization of ADAMTS13 activity during caplacizumab therapy has been identified. In a retrospective analysis, we compared platelet count, ADAMTS13 activity, its inhibitor, and anti-ADAMTS13 immunoglobulin G (IgG) levels in acute iTTP cases treated with caplacizumab (n = 14) or without it (n = 16). The median time from initial therapeutic plasma exchange (TPE) to the first rituximab administration was 12 days in the caplacizumab group (n = 11) and 10 days in the group without caplacizumab (n = 13). We evaluated ADAMTS13-related parameters at onset and once a week until day 28 after the first TPE. The number of days until the platelet counts reached ≥150 × 109/L was significantly shorter in the caplacizumab group than in the non-caplacizumab group. The median ADAMTS13 activity levels on days 14, 21, and 28 were significantly lower in the caplacizumab group. The median titers of the ADAMTS13 inhibitor and anti-ADAMTS13 IgG on the same days were significantly higher in the caplacizumab group. Furthermore, the median number of days from the first TPE until finally achieving an ADAMTS13 activity of ≥10% was significantly longer in the caplacizumab group than in the non-caplacizumab group (42 vs 23 days, P = .014). We observed delayed ADAMTS13 activity recovery and continued inhibitor and anti-ADAMTS13 IgG detection in patients with acute iTTP on caplacizumab, possibly because of the decreased number of TPEs and delayed frontline rituximab.

Saito K ，Sakai K ，Kubo M ，Azumi H ，Hamamura A ，Ochi S ，Amagase H ，Kunieda H ，Ogawa Y ，Yagi H ，Matsumoto M ... -  《-》

ADAMTS13 recovery in acute thrombotic thrombocytopenic purpura after caplacizumab therapy.

Mingot-Castellano ME ，García-Candel F ，Martínez-Nieto J ，García-Arroba J ，de la Rubia-Comos J ，Gómez-Seguí I ，Paciello-Coronel ML ，Valcárcel-Ferreiras D ，Jiménez M ，Cid J ，Lozano M ，García-Gala JM ，Angós-Vazquez S ，Vara-Pampliega M ，Guerra-Domínguez L ，Ávila-Idrobo LF ，Oliva-Hernandez A ，Zalba-Marcos S ，Tallón-Ruiz I ，Ortega-Sánchez S ，Goterris-Viciedo R ，Moreno-Jiménez G ，Domínguez-Acosta L ，Araiz-Ramírez M ，Hernández-Mateos L ，Flores-Ballesteros E ，Del Río-Garma J ，Pascual-Izquierdo C ... -  《-》

Management of immune thrombotic thrombocytopenic purpura with caplacizumab: a Canadian, single-centre, real-world experience.

Tse B ，Buchholz M ，Pavenski K 《-》