Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study

Bussel, James B.; Miguel, Purificación García de; Despotovic, Jenny M.; Grainger, John D.; Sevilla, Julián; Blanchette, Victor S.; Krishnamurti, Lakshmanan; Connor, Philip; David, Michèle; Boayue, Koh; Matthews, Dana C.; Lambert, Michele P.; Marcello, Lisa M; Iyengar, Malini; Chan, Geoffrey; Chagin, Karen; Theodore, Dickens; Bailey, Christine K; Bakshi, Kalpana

doi:10.1016/s2352-3026(15)00114-3

Cited by 159 publications

(243 citation statements)

References 39 publications

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“…20 Eltrombopag is metabolized primarily through the CYP1A2 and CYP2C8 enzymes (to form a mono-oxygenation product) and UGT1A1 and UGT1A3 (to form a glucuronide conjugate), although in humans, most of the circulating eltrombopag is excreted as unchanged drug. 21 These characteristics may help explain the observed hepatoxicity (the drug is primarily metabolized and cleared by the liver), as discussed below.…”

Section: Drug Metabolismmentioning

confidence: 99%

“…PETIT and PETIT2 were phase 2 and 3 randomized, multicenter, placebo-controlled trials. 21,24 Children age 1 to 17 years with ITP that lasted for 6 months or more and a platelet count of ,30 3 10 9 /L at enrollment who had received at least 1 prior therapy for ITP were included. Patients who were receiving stable doses of therapy for chronic ITP were permitted to continue with concomitant therapies.…”

Section: Pediatric Trialsmentioning

confidence: 99%

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Eltrombopag for use in children with immune thrombocytopenia

2018

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Eltrombopag is currently the only US Food and Drug Administration–approved thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia (ITP) in children. This oral, once-per-day therapy has shown favorable efficacy and adverse effect profiles in children. Two multicenter, double-blind, placebo controlled clinical trials (PETIT [Efficacy and Safety Study of Eltrombopag in Pediatric Patients With Thrombocytopenia From Chronic Idiopathic Thrombocytopenic Purpura (ITP)] and PETIT2 [Study of a New Medication for Childhood Chronic Immune Thrombocytopenia (ITP), a Blood Disorder of Low Platelet Counts That Can Lead to Bruising Easily, Bleeding Gums, and/or Bleeding Inside the Body]) demonstrated efficacy in raising platelet counts, reducing bleeding, and reducing the need for concomitant ITP therapies with relatively few adverse effects. The most commonly reported drug-related adverse effects include headache, nausea, and hepatobiliary laboratory abnormalities. Long-term safety data in children are limited, and studies in adults have not revealed a clinically significant increased incidence of thrombosis, marrow fibrosis, or cataract formation. Eltrombopag has also been approved for treating refractory severe aplastic anemia (AA) and has potential for expanded use in ITP and severe AA as well as in other conditions associated with thrombocytopenia.

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Section: Drug Metabolismmentioning

confidence: 99%

Section: Pediatric Trialsmentioning

confidence: 99%

Eltrombopag for use in children with immune thrombocytopenia

2018

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“…There are currently two US Food and Drug Administration (FDA)-approved TPO-RAs, eltrombopag and romiplostim. These agents have both been extensively studied in adults and children with chronic ITP [24][25][26][27][28][29][30][31][32][33] ; however, their use as therapy for newly diagnosed patients remains unclear. Although the primary mechanism of the TPO-RAs is not immunomodulatory, changes in the immune profile with increase in T regulatory cells have been shown after use.…”

Section: Thrombopoietin-receptor Agonistsmentioning

confidence: 99%

Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

Neunert

2017

Blood Advances

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Immune thrombocytopenia resulting from antibody-mediated platelet destruction combined with impaired platelet production is a common cause of thrombocytopenia. The decision to treat newly diagnosed patients is based on several factors including ceasing hemorrhagic manifestations, increasing the platelet count, prevention of bleeding, and inducing remission.Current standard first-line therapy is a course of corticosteroids. Although this treatment paradigm increases the platelet count in the majority of patients, a high percentage relapse after discontinuation of corticosteroid therapy. For this reason, intensification of first-line therapy that results in superior long-term remission rates would be desirable. This manuscript focuses primarily on adults with idiopathic thrombocytopenic purpura (ITP), highlighting pediatric data and practice when applicable. The primary aim is to outline upfront strategies for treatment-naive patients with ITP to enhance remission rates, taking into account assessment of the risks and benefits of these approaches.

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“…Less than 10% of patients enrolled in the PETIT trials had been previously splenectomized. 33,34 The TRAs are generally well tolerated. In a pooled analysis of 14 trials of adults with ITP treated with romiplostim, bone marrow reticulin was observed in 17 of 921 patients.…”

Section: Tiermentioning

confidence: 99%

How I treat refractory immune thrombocytopenia

Cuker

Neunert

2016

Blood

124

129

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This article summarizes our approach to the management of children and adults with primary immune thrombocytopenia (ITP) who do not respond to, cannot tolerate, or are unwilling to undergo splenectomy. We begin with a critical reassessment of the diagnosis and a deliberate attempt to exclude nonautoimmune causes of thrombocytopenia and secondary ITP. For patients in whom the diagnosis is affirmed, we consider observation without treatment.Observation is appropriate for most asymptomatic patients with a platelet count of 20 to 30 3 10 9 /L or higher. We use a tiered approach to treat patients who require therapy to increase the platelet count. Tier 1 options (rituximab, thrombopoietin receptor agonists, low-dose corticosteroids) have a relatively favorable therapeutic index. We exhaust all Tier 1 options before proceeding to Tier 2, which comprises a host of immunosuppressive agents with relatively lower response rates and/or greater toxicity. We often prescribe Tier 2 drugs not alone but in combination with a Tier 1 or a second Tier 2 drug with a different mechanism of action. We reserve Tier 3 strategies, which are of uncertain benefit and/or high toxicity with little supporting evidence, for the rare patient with serious bleeding who does not respond to Tier 1 and Tier 2 therapies. (Blood. 2016;128(12): 1547-1554 Case 1A 10-year-old male was diagnosed with primary immune thrombocytopenia (ITP) 5 months ago when he presented with epistaxis, petechiae, bruising, and a platelet count of 5 3 10 9 /L. He responded transiently to intravenous immunoglobulin G (IgG), but epistaxis recurred 2 weeks later. He subsequently received a short course of oral corticosteroids to which he had a temporary response in platelet count and cessation of epistaxis. Since discontinuing corticosteroids, he has had only occasional bruising and petechiae. His platelet count is currently 13 3 10 9 /L. He states that ITP is not interfering with activities.

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Eltrombopag for the treatment of children with persistent and chronic immune thrombocytopenia (PETIT): a randomised, multicentre, placebo-controlled study

Cited by 159 publications

References 39 publications

Eltrombopag for use in children with immune thrombocytopenia

Eltrombopag for use in children with immune thrombocytopenia

Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

How I treat refractory immune thrombocytopenia

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