Long Term Eltrombopag in Paediatric Immune Thrombocytopenia: Update on UK Patients Treated with Eltrombopag As Part of the Petit and PETIT2 Studies

Introduction: The use of Eltrombopag in children with chronic ITP was investigated by the PETIT and later, the PETIT2, trials. We report the ongoing long-term UK follow up data from the patients who featured on those trials based over two UK sites.

Method: Twelve children in total were commenced on Eltrombopag as per the PETIT and PETIT2 trial protocols located over two UK sites; Manchester (n=7), Cardiff (n=5). Eleven children were included in long term analysis. One child was withdrawn from the trial due to lack of efficacy and increased reticulin (of two grades). The mean age when commencing trial was 12.1 years, total age range 4.4 - 17.4 years. Treatment with Eltrombopag was commenced between October 2009 and Sep 2012; data was assessed from the start date until June 2017. The mean duration of treatment on Eltrombopag was 49 months (range 6-88 months) with the duration of follow up varying from 60-94 months. Two patients included in the data ended treatment with Eltrombopag and were commenced on Romiplostim. All patients had received previous alternative treatments for ITP prior to commencing Eltrombopag: prednisolone alone (n=5), prednisolone, intravenous immunoglobulin (IVIG) and platelet transfusion (n=2), IVIG alone (n=2), IVIG and Rituximab (n=2). All patients were off concomitant medications prior to commencing Eltrombopag. All patients had bone marrow assessment prior to commencing treatment and 8 patients had documented repeated bone marrow assessment whilst on or post-treatment.

Results: Of the 11 patients, 4 treated on the trials no longer require platelet-enhancing therapy to maintain a safe platelet level. Last recorded platelet count for patients who remained off treatment ranged from 65-156x10⁹/l (mean value 119x10⁹/l). One patient who remains on Eltrombopag treatment maintained a treatment holiday of 12 months duration prior to recommencing treatment. A further 6 patients remain on treatment, with sustained response and no significant adverse events reported (mean treatment period 72.8 months, range: 55 - 91 months). Two patients were commenced on Romiplostim after a period of treatment with Eltrombopag. Reasons for discontinuation of treatment include grade <1 lens opacification (n=1) and loss of response to therapy after 10 months duration (n=1). One patient continues to use Romiplostim with a sustained response. The other was switched to Romiplostim in November 2011 and was able to stop all treatment by January 2017.

Observed events included subclinical, grade <1, ocular lens changes (n=2) however both had received prior steroid therapy. No hepatotoxicity was reported. Bone marrow assessment during or post-treatment was completed in 8 patients with no demonstrable significant reticulin increase (defined as less than two reticulin grades).

Conclusion: We report the long-term use of the oral thrombopoietin agonist Eltrombopag in association with sustained safe and acceptable platelet level in chronic ITP in a UK paediatric population enabling treatment to be discontinued (4 of 11 patients) and one further patient had a remission for 12 months prior to recommencement of a platelet-enhancing agent. A further 6 patients continue on long-term Eltrombopag treatment maintaining a satisfactory response. The data highlights no new safety concerns regarding the long-term use of Eltrombopag in the paediatric population including no late liver function abnormalities.