ADAMTS13 Antibody Depletion by Bortezomib in Thrombotic Thrombocytopenic Purpura

Shortt, Jake; Oh, Danielle H.; Opat, Stephen

doi:10.1056/nejmc1213206

Cited by 109 publications

(110 citation statements)

References 4 publications

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“…Recently, it has been proposed for the treatment of refractory TTP, based on the hypothesis that residual anti-ADAMTS13 antibodies produced by plasma cells resistant to the usual immunosuppressive therapies could be eliminated by this drug. 28,29 Although single cases suggest that bortezomib is effective, the contribution of other immunosuppressive treatments introduced concomitantly or even the natural history of the disease cannot be excluded. Therefore, this approach needs to be evaluated in prospective clinical trials.…”

Section: Cyclophosphamidementioning

confidence: 99%

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Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Coppo

Froissart

2015

Hematology

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Daily therapeutic plasma exchange (TPE) transformed the historically fatal prognosis of acquired, anti-ADAMTS13 antibody-mediated thrombotic thrombocytopenic purpura (TTP), leading to the current overall survival rates of 80%-85%. However, relapses occur in ϳ40% of patients and refractory disease with fatal outcomes still occurs. In this context, the introduction of rituximab has probably been the second major breakthrough in TTP management. Rituximab is now routinely recommended during the acute phase, typically in patients with a suboptimal response to treatment, or even as frontline therapy, with high response rates. In more severe patients, salvage strategies may include twice-daily TPE, pulses of cyclophosphamide, vincristine, as well as splenectomy in more desperate cases.In this life-threatening disease, relapse prevention represents a major goal. Persistent severe acquired ADAMTS13 deficiency in patients who are otherwise in remission is associated with a high risk of relapse and preemptive treatment with rituximab may be considered in this context.In the coming years, the TTP therapeutic landscape should be enriched by original strategies stemming from clinical experience and new agents that are currently being evaluated in large, ideally international, clinical trials. Promising agents under evaluation include N-acetylcysteine, bortezomib, recombinant ADAMTS13, and inhibitors of the glycoprotein-Ib/IX-von Willebrand factor axis. Learning Objectives• Patients with acquired TTP who experience a suboptimal response (refractoriness or disease exacerbation) with standard management need a more intensive treatment • Salvage therapies typically include rituximab, and in the more severe cases twice daily plasma exchange, boluses of cyclophosphamide, vincristine, and splenectomy • A persistent severe acquired ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses

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Section: Cyclophosphamidementioning

confidence: 99%

“…26 However, some failures were also reported. 27,28 Considering the limited toxicity of NAC, its use as adjunctive treatment in TTP seems interesting and needs to be further evaluated.…”

Section: Cyclophosphamidementioning

confidence: 99%

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Coppo

Froissart

2015

Hematology

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“…Its mechanism of action in TTP is thought to be due to the elimination of plasma cells that produce the autoantibodies against ADAMTS13. The evidence for the use of this drug is still limited to case reports35, 40, 41, 42, 43, 44, 45 and a case series37 that reported 14 cases of TTP that were refractory to PEX, steroids, and rituximab. All but one patient recovered from their acute episode of TTP.…”

Section: Bortezomibmentioning

confidence: 99%

Novel therapies in thrombotic thrombocytopenic purpura

Masias

Cataland

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials The standard of care for patients with TTP remains daily plasma exchange in addition to immune suppressive therapy.Despite the improved treatment options for TTP, the acute mortality of TTP remains between 15‐20%.Caplacizumab reduces the time to platelet recovery and the exacerbation rate in acute TTP.A better understanding of the cause and treatments of long‐term complications of TTP are needed. Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and a consumptive thrombocytopenia, as a result of severe deficiency of ADAMTS13. The standard of care of the acute episode is treatment with plasma exchange and immunosuppression. After the acute episode is resolved, patients face a significant risk of relapse and long‐term complications associated with significant morbidity and even mortality. Novel treatments have been under development and will be discussed in this review. Caplacizumab, a nanobody that blocks the interaction between VWF and platelets, has shown promising results in decreasing the time to recover from the acute events that will hopefully translate into long‐term clinical benefit for patients. In addition, identifying biomarkers to allow us to better predict the risk for relapse and the development of these long‐term complications in patients with TTP are a few of the challenges that require our attention moving forward.

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“…The relapse rates after rituximab treatment ranged from 0% with a median follow-up of 10 months (47) to 33% with a median follow-up of 73 months (52). Patients who are refractory to plasmapheresis, corticosteroids and rituximab may benefit from bortezomib administration (53)(54)(55).…”

Section: Differential Diagnosis Of Ttpmentioning

confidence: 99%

Thrombotic Thrombocytopenic Purpura: Etiopathogenesis, Diagnostics and Basic Principles of Treatment

Todorović

Petrović

et al. 2017

Serbian Journal of Experimental and Clinical Research

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Th rombotic thrombocytopenic purpura (TTP) is a clinical syndrome that manifests with thrombocytopenia, microangiopathic haemolytic anaemia and symptoms and signs of kidney and brain damage, but it rarely involves other organs. Th e main pathophysiological cause of TTP is diminished metalloproteinase ADAMTS13 activity; the main function of ADAMTS13 is to degrade large multimers of the von SAŽETAK Trombotična trombocitopenijska purpura (TTP) je klinički sindrom koji se odlikuje trombocitopenijom, mikroangiopatskom hemoliznom anemijom i simptomima i znacima oštećenja bubrega i mozga, ređe drugih organa. Glavni patofi ziološki mehanizam nastanka TTP-a je smanjena aktivnost metaloproteinaze ADAMTS13 čija je osnovna uloga razgradnja velikih multimera von Willebrand-ovog faktora. Smanjena aktivnost metaloproteinaze ADAMTS13 nastaje usled mutacije u genu za ADAMTS13 (urođeni TTP) ili usled nastanka antitela koja blokiraju ili antitela koja ubrzavaju razgradnju ADAMTS13 (stečeni TTP

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ADAMTS13 Antibody Depletion by Bortezomib in Thrombotic Thrombocytopenic Purpura

Cited by 109 publications

References 4 publications

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Treatment of thrombotic thrombocytopenic purpura beyond therapeutic plasma exchange

Novel therapies in thrombotic thrombocytopenic purpura

Thrombotic Thrombocytopenic Purpura: Etiopathogenesis, Diagnostics and Basic Principles of Treatment

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