A single-arm, long-term efficacy and safety study of subcutaneous romiplostim in children with immune thrombocytopenia

Romiplostim is a thrombopoietin (TPO) receptor agonist approved for children and adults with immune thrombocytopenia (ITP) for >= 6 months, recommended as second-line treatment. This phase 3b, single-arm, multicenter study investigated long-term efficacy and safety of romiplostim in children >= 1 to <18 years old with >= 6 months' ITP duration and platelet counts <= 30 x 10(9)/L. Children received weekly subcutaneous romiplostim (1 mu g/kg titrated to 10 mu g/kg) to maintain platelets within 50 to 200 x 10(9)/L. A subset underwent bone marrow examinations. The primary end point was percentage of time with platelet response during the first 6 months' treatment (counts >= 50 x 10(9)/L without rescue medication within the preceding 4 weeks). Overall, 203 patients (median age, 10.0 years) received >= 1 dose of romiplostim, median treatment duration was similar to 3 years, and median average weekly dose was 6.9 mu g/kg. Ninety-five (46.8%) discontinued (lack of efficacy, n = 43 [21.2%]). Platelet responses were achieved a median (interquartile range) of 50.0% (16.7%-83.3%) of the time during the first 6 months, increasing to 78.2% (26.7%-90.4%) during the overall 36-month treatment period. Eleven patients (5.4%) achieved sustained responses (consecutive counts >= 50 x 10(9)/L without ITP medications for >= 24 weeks). Treatment-related adverse events (AEs) occurred in 56 patients (27.6%), with 8 (3.9%) experiencing serious treatment-related AEs; all of these led to discontinuation, including 4 cases of neutralizing antibodies (romiplostim, n = 3; TPO, n = 1). Bleeding occurred in 141 patients (69.5%), decreasing over time; grade >= 3 bleeding events occurred in 20 (9.9%). At year 2, eight of 63 evaluable patients (12.7%) had grade 2 reticulin. Long-term romiplostim resulted in sustained on-treatment platelet responses with an overall safety profile consistent with previous studies. This trial was registered at www.clinicaltrials.gov as #NCT02279173.

Automated summary

This study investigated the long-term efficacy and safety of romiplostim in children with immune thrombocytopenia (ITP) for at least 6 months. The results showed that romiplostim can maintain platelet counts within the desired range and achieve platelet responses for a significant proportion of the treatment period. The use of romiplostim in the long term resulted in sustained platelet responses and demonstrated a consistent safety profile.