Rituximab for thrombotic thrombocytopenic purpura: lessons from the STAR trial

Uhl, Lynne; Kiss, Joseph E.; Malynn, Elizabeth; Terrell, Deirdra R.; Vesely, Sara K.; George, James N.

doi:10.1111/trf.14193

Cited by 19 publications

(22 citation statements)

References 17 publications

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“…Clinical studies in iTTP have been limited by the low incidence of this disease. In particular, conventional methods (eg, randomized controlled trials) are challenging in TTP, except for extremely expensive and lengthy pharmaceutical trials . However, over the past few years, several groups have established large registries that include hundreds of patients.…”

Section: How To Improve Ttp Management?mentioning

confidence: 99%

“…The introduction of the humanized anti‐CD20 monoclonal antibody rituximab has been the second major breakthrough in iTTP management. Clinical studies conducted to assess the role of rituximab in iTTP have faced the usual challenges that confront clinical trials in rare diseases such as difficulty with recruitment and cross‐over . These challenges are compounded in iTTP by the necessity to intervene rapidly, leaving little time for determination of eligibility and informed consent.…”

Section: Immunomodulation Through B‐cell Depletion: Where Do We Stand?mentioning

confidence: 99%

“…Clinical studies conducted to assess the role of rituximab in iTTP have faced the usual challenges that confront clinical trials in rare diseases such as difficulty with recruitment and cross-over. 21 These challenges are compounded in iTTP by the necessity to intervene rapidly, leaving little time for determination of eligibility and informed consent. As such, current knowledge about the use of rituximab in iTTP is based on observational studies that enrolled a limited number of patients and provide low to moderate levels of evidence.…”

Section: Immunomodulation Through B-cell Depletion: Where Do We Stand?mentioning

confidence: 99%

“…Diagnosis of iTTP in an emergency setting is challenged by the rarity of the disease and nonspecificity of presenting signs and symptoms, which may lead to a delay in initiation of treatment. 11,21 Although the diagnosis of iTTP is still delayed in some patients, clinicians are becoming increasingly aware of this condition.…”

Section: Make Clinicians More Aware Of Ttp Diagnosismentioning

confidence: 99%

“…Clinical studies in iTTP have been limited by the low incidence of this disease. In particular, conventional methods (eg, randomized controlled trials) are challenging in TTP, 21…”

Section: Improve the Level Of Evidence Of Therapeutic Studies In Ttpmentioning

confidence: 99%

See 4 more Smart Citations

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine

Coppo

Cuker

George

2019

Research and Practice in Thrombosis and Haemostasis

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112

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Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by severe congenital or immune‐mediated deficiency in ADAMTS13, the enzyme that cleaves von Willebrand factor multimers. This rare condition leads invariably and rapidly to a fatal outcome in the absence of treatment, and therefore raises multiple diagnostic and therapeutic challenges. The novel concepts and mechanisms identified in the laboratory for this disease have been rapidly and successfully translated into the clinic for the benefit of patients, making TTP an archetypal disease that has benefited from targeted therapies. After decades of empirical treatment with plasma exchange, identification of ADAMTS13 as the key enzyme involved in TTP pathophysiology provided an explanation for the remarkable efficacy of plasma administration, in which the missing enzyme is replenished, and paved the way for development of a recombinant form of the enzyme. Similarly, the demonstration of a major role of anti‐ADAMTS13 antibodies through models of passive transfer of autoimmunity spurred development of immunomodulatory strategies based on B‐cell depletion. More recently, an inhibitor of the platelet‐von Willebrand factor interaction demonstrated efficacy in large clinical trials through prevention of formation of further microthrombi and protection of organs from ischemia. These translational breakthroughs in TTP are described in our review.

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Section: How To Improve Ttp Management?mentioning

confidence: 99%

Section: Immunomodulation Through B‐cell Depletion: Where Do We Stand?mentioning

confidence: 99%

Section: Immunomodulation Through B-cell Depletion: Where Do We Stand?mentioning

confidence: 99%

Section: Make Clinicians More Aware Of Ttp Diagnosismentioning

confidence: 99%

“…Clinical studies in iTTP have been limited by the low incidence of this disease. In particular, conventional methods (eg, randomized controlled trials) are challenging in TTP, 21…”

Section: Improve the Level Of Evidence Of Therapeutic Studies In Ttpmentioning

confidence: 99%

See 3 more Smart Citations

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine

Coppo

Cuker

George

2019

Research and Practice in Thrombosis and Haemostasis

Self Cite

112

View full text Add to dashboard Cite

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Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired thrombotic thrombocytopenic purpura

Al‐Samkari¹,

Grace

Connors

2018

J Thromb Thrombolysis

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Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder resulting in potentially life-threating systemic thrombotic microangiopathy due to production of antibodies directed against the von Willebrand factor-cleaving protease ADAMTS13. Typically managed with plasma exchange, glucocorticoids, and the first-generation anti-CD20 monoclonal antibody rituximab, patients with multiple relapses or refractory disease present unique management challenges. We describe a case of a young woman with multiple relapses of TTP despite standard therapy who was treated with ofatumumab, a second-generation anti-CD20 monoclonal antibody, after developing a severe hypersensitivity reaction to rituximab precluding its use. Ofatumumab was effective for the treatment of an acute relapse of TTP in combination with plasmapheresis and as a single-agent for prophylaxis. The patient has had no evidence of relapse 2 years after completion of acute treatment and 1 year after completing prophylactic therapy. Hypersensitivity to ofatumumab did not develop.

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Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023

Matsumoto,

Miyakawa,

Kokame

et al. 2023

Int J Hematol

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Thrombotic thrombocytopenic purpura (TTP) can rapidly become a life-threatening condition, and the importance of its appropriate diagnosis and treatment cannot be overstated. Until recently, TTP has mainly been diagnosed by clinical findings such as thrombocytopenia and hemolytic anemia. In addition to these clinical findings, however, reduced activity of a disintegrin-like and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13) below 10% has become internationally accepted as a diagnostic criterion for TTP. TTP is classified as immune-mediated TTP (iTTP) if the patient is positive for anti-ADAMTS13 autoantibodies, and as congenital TTP (cTTP) if ADAMTS13 gene abnormalities are detected. Fresh frozen plasma (FFP) transfusion is performed in patients with cTTP to supplement ADAMTS13. Plasma exchange therapy using FFP is conducted in patients with iTTP to supplement ADAMTS13 and to remove both anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor (VWF) multimers. To suppress autoantibody production, corticosteroid therapy is administered in conjunction with plasma exchange. The monoclonal anti-CD-20 antibody rituximab is effective in patients with iTTP. In addition, caplacizumab, an anti-VWF A1 domain nanobody, has a novel mechanism of action, involving direct inhibition of platelet glycoprotein Ib–VWF binding. The recommended first-line treatments of iTTP in Japan are plasma exchange and corticosteroids, as well as caplacizumab.

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Rituximab for thrombotic thrombocytopenic purpura: lessons from the STAR trial

Abstract: ABBREVIATIONS: BMI 5 body mass index; DSMB 5 Data Safety Monitoring Board; RCT(s) 5 randomized controlled trial(s); TMH CTN 5 Transfusion Medicine/Hemostasis Clinical Trials Network; TPE 5 therapeutic plasma exchange; TTP 5 thrombotic thrombocytopenic purpura. From the

Cited by 19 publications

References 17 publications

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine

Thrombotic thrombocytopenic purpura: Toward targeted therapy and precision medicine

Ofatumumab for acute treatment and prophylaxis of a patient with multiple relapses of acquired thrombotic thrombocytopenic purpura

Diagnostic and treatment guidelines for thrombotic thrombocytopenic purpura (TTP) in Japan 2023

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