Use of Thrombopoietin Receptor Agonists in Childhood Immune Thrombocytopenia

Abstract

Most children with immune thrombocytopenia (ITP) will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long-term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA) have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data are emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long-term safety issues that need to be considered when using these agents.

The Centenary of Immune Thrombocytopenia—Part 2: Revising Diagnostic and Therapeutic Approach

“…Since the discovery of the role of thrombopoietin (TPO) in ITP several thrombopoietic drugs was tested ( 113 ), and in 2008 FDA approved two TPO receptor agonists for non-responsive ITP in adults: romiplostim and eltrombopag ( 114 , 115 ). Romiplostim acts on TPO-binding subunit of the receptor and is administered subcutaneously weekly ( 116 ). It is not yet approved for childhood-onset ITP, although in several studies it showed a 50–80% response rate, without severe adverse effects ( 117 – 125 ).…”

“…Eltrombopag acts binding the transmembrane domain of TPO receptor and is administered orally daily ( 116 ). It showed response rates greater than 60% in two randomized trials, associated with a good tolerability ( 126 , 127 ), so in 2015 FDA has approved it for the use in childhood-onset disease.…”

A Phase 3, Randomized, Double‐Blind, Placebo‐Controlled Study to Determine the Effect of Romiplostim on Health‐Related Quality of Life in Children with Primary Immune Thrombocytopenia and Associated Burden in Their Parents

“…Traditional treatments have included corticosteroids, intravenous immunoglobulin, and anti‐D immune globulin. Immunosuppressive agents, used singly or in combination, and splenectomy are typically second‐line therapies in children with primary, chronic ITP . The treatment with immunoglobulins is more common in children (including among those hospitalized with newly diagnosed ITP), while corticosteroids are used more frequently in adults …”

“…Immunosuppressive agents, used singly or in combination, and splenectomy are typically second-line therapies in children with primary, chronic ITP. [9,14,15] The treatment with immunoglobulins is more common in children (including among those hospi-talized with newly diagnosed ITP [16]), while corticosteroids are used more frequently in adults. [17] This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.…”

The Centenary of Immune Thrombocytopenia – Part 1: Revising Nomenclature and Pathogenesis

“…These studies opened an interesting window of opportunity, indicating TPO receptor agonists (TPO-RA) as an alternative treatment option for children with chronic ITP. Clinical trials in children are ongoing and data are emerging on safety and efficacy of these agents ( 61 ). Although the autoantibodies-mediating accelerated platelet clearance from the circulation continues to be the central theme in the current understanding of ITP, its pathogenesis appears to be multifactorial, resulting as a complex interplay involving multiple components of the immune system (Figures 2 and 3 ).…”