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Figure 1. (Left) Currently, children who present with immune thrombocytopenia (ITP) are followed without therapy in the absence of significant bleeding. Life-threat- ening bleeding is rare, remission is common, and no therapy has been shown to alter the natural history of the disorder. The decision not to treat is therefore dom- inated by the side effects of therapy. The side effects of corticosteroids and intravenous immunoglobulin (IVIG) and the risk of infection after splenectomy and per- haps rituximab mitigate in favor of observation. Indeed, treatment may worsen health care related quality of life (HRQol). (Right) With the advent of thrombopoietin receptor agonists (TRA), the proper balance has become less clear. TRA provide a therapeutic option with a high response rate and fewer concerns about side effects, as described in Tarentino et al.1 Improvement in platelet counts may reduce nuisance bleeding and the need for rescue therapy and hospital attendance, increase participation in physical and social activities, reduce anxiety around low platelet counts, and improve HRQoL. ICH: intracranial hemorrhage; Rx: treatment.
year (range: 0.4-2.1 years); younger age at first dose was associated with treatment-free responses.
This is the most comprehensive placebo-controlled study of TRA in pediatric ITP. The data show that romi- plostim is a highly effective maintenance therapy for chil- dren with ITP of at least six months duration who did not respond to, or perhaps were intolerant of, prior therapies and who experienced bleeding or are at risk of bleeding because of low platelet counts. Romiplostim was well tolerated, no significant drug-related AE were observed at two years of study, and, importantly, treatment could be given at home by trained patients or family members. The high rate of withdrawal complicates delineating sus- tained reduction in bleeding events, use of concurrent medications, and the need for rescue interventions that might occur with more extended use in practice. Also, the implication that romiplostim induces remission is less compelling in the absence of a control population.
Eltrombopag has also been approved for use in the pediatric population in a similar setting and with similar outcomes.15-18 Iron deficiency and transaminitis have been reported in some children treated with eltrombopag.16,19 One as yet theoretical concern when contemplating long- term use is that eltrombopag acts on bone marrow stem cells as well as on megakaryocytes.20 In the absence of a head-to-head study, the choice between agents often comes down to the requirement for dietary restrictions and daily administration with eltrombopag versus par- enteral administration with more frequent medical visits
with romiplostim, as well as differences in cost and insur- ance coverage.
One important issue raised by this study is whether consideration should be given to starting romiplostim or eltrombopag in children with ITP without the need to wait six months from diagnosis. This is particularly rele- vant for children who experience extensive bruising, epis- taxis, menorrhagia, or other symptoms that require fre- quent medical interventions or that lead to loss of school days, withdrawal from competitive sports or otherwise reduce HRQol (Figure 1, right). If durable safety is estab- lished, TRA may also be advantageous for those with less severe symptoms but significant anxiety related to low platelet counts. Indeed, this trend in treatment is becom- ing apparent, as approximately 20% of the children treat- ed with romiplostim in the ICON2 analysis had severe, refractory, but newly diagnosed ITP, and a few were treated to resume physical activities or to improve QoL.17 Improvements in platelet count and HRQol have been reported with this approach, although the number of patients studied is small and the duration of follow up is short.18,21
In addition to continued surveillance relating to safety in the pediatric population, future studies are needed to determine if initiating treatment earlier in the disease reduces bleeding, the need for other treatment, medical visits, and lost school days while improving the emotion- al well-being of the child and the family. Therefore, stud- ies such as the one reported here by Tarantino et al. could
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