Romiplostim May Increase Platelet Response in Children with Chronic Immune Thrombocytopenia

EBM Focus - Volume 11, Issue 28

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Reference - Lancet 2016 Jul 2;388(10039):45 (level 3 [lacking direct] evidence)

  • Current therapies for children with immune thrombocytopenia (ITP) have variable response rates and come with risk of serious adverse events, but data for the use of thrombopoietin receptor agonists in children are limited.
  • Romiplostim significantly increased the rates of durable platelet response (platelet response for at least 6 of 8 final treatment weeks) and overall platelet response compared to placebo in a trial including 62 children, but did not appear to increase the rates of adverse events.
  • Optimal romiplostim doses were not reached until treatment week 14, limiting the ability to determine differences in bleeding outcomes over the 24 week trial.

While most children with ITP attain spontaneous remission within a few months with or without treatment, approximately 30% of children will develop persistent or chronic ITP requiring treatment to maintain hemostatic platelet counts (Br J Haematol 2014 Jun;165(6):756). Currently recommended therapies for persistent ITP include rituximab, high-dose corticosteroids, or splenectomy (Hematology Am Soc Hematol Educ Program 2013;2013:276, Blood 2010 Jan 14;115(2):168), but these therapies come with risks and have variable response rates. Romiplostim, a thrombopoietin receptor agonist, is approved for use in adults with ITP. It has been found to improve platelet response and reduce bleeding events as well as the need for splenectomy (N Engl J Med 2010 Nov 11;363(20):1889, Lancet 2008 Feb 2;371(9610):395). However, data are limited for children. A recent trial randomized 62 children with ITP for > 6 months, a mean platelet count ≤ 30 × 109/L, and no platelet count > 35 × 109/L to romiplostim vs. placebo for 24 weeks. Romiplostim was titrated from 1 mcg/kg up to a maximum dose of 10 mcg/kg or until a platelet count of ≥ 50 × 109/L was reached.

All children had at least 1 previous therapy or were ineligible for other ITP therapies, though children with recent rituximab therapy (within 14 weeks) or splenectomy (within 4 weeks) were excluded. The primary outcome was a durable platelet response, defined as a weekly platelet response (a platelet count ≥ 50 × 109/L without rescue medication in the prior 4 weeks) for at least 6 of the final 8 weeks of treatment. Overall, 52% of children with romiplostim achieved a durable platelet response vs. 10% of children with placebo (p = 0.002, NNT 3). These results were consistent across all age groups, although the rate of durable platelet response and the difference between groups was smallest for children aged 1-6 years. The overall platelet response was 71% with romiplostim vs. 20% with placebo (p = 0.0002, NNT 2) and the median time to response was 4.5 weeks vs. 20 weeks (p = 0.03). Comparing romiplostim vs. placebo, serious adverse events were reported in 24% vs. 5%, although only one child was considered to have treatment-related serious adverse events. The most common adverse events (occurring in ≥ 30% of children) were headache, epistaxis, contusion, and upper respiratory tract infection, but no patients withdrew due to adverse events. There were no significant differences in the overall rates of bleeding or use of rescue medication.

The results of this trial suggest that romiplostim is a safe and effective option in children with chronic ITP. However the dose of romiplostim was not fully titrated until approximately week 14 and platelet counts rose consistently along with the increasing doses. The relatively short amount of time at the optimal dose may not have allowed for a true assessment of bleeding outcomes. Furthermore, although this trial evaluated the rates of platelet response in 3 age groups (1 to < 6, 6 to < 12, and 12 to< 18), the trial was not powered to detect differences in these subgroups. The observation that the youngest children had the lowest response rate is consistent with trials evaluating eltrombopag, another thrombopoietin receptor agonist (Lancet 2015 Oct 24;386(10004):1649, Lancet Haematol 2015 Aug;2(8):e315), but these trials were also underpowered to determine the significance of these differences. Overall, these results suggest that romiplostim may be safe and effective for children with ITP, but larger studies are needed before its use can be confidently recommended.

For more information, see the Immune thrombocytopenia (ITP) in children in DynaMed.