Spotlight on eltrombopag in pediatric ITP in China: a long-term observational study in real-world practice

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with isolated thrombocytopenia and risk of hemorrhage. Treatment with eltrombopag increases and maintains hemostatic platelet counts; however, to date, long-term data are lacking on the outcome of children with ITP who are treated with eltrombopag. This prospective, observational, longitudinal cohort study evaluated the efficacy and safety of eltrombopag in pediatric patients with persistent or chronic ITP. For the 116 pediatric patients enrolled, duration of eltrombopag treatment was at least 3 months. Median effective dose was 25 mg/day, 50 mg/day, and 50 mg/day, respectively, for children age 5 years or younger, 6 to 11 years, or 12 years or older. In all, 89 patients (76.7%) achieved overall response, 53 (45.7%) achieved complete response, and 36 (31.0%) achieved response. Median platelet counts increased by week 1 and were sustained throughout the treatment period. During treatment with eltrombopag, the proportion of patients with grade 1 to 4 bleeding symptoms decreased from 83.61% at baseline to 9.88% at 6 months when only grade 1 was reported. Forty-three patients (37.1%) reported using concomitant medications at study entry, which was reduced to 1 patient (2.5%) who needed concomitant medications at 12 months. All adverse events were grade 1 or 2 according to Common Terminology Criteria for Adverse Events. No serious adverse events, cataracts, malignancies, or thromboses were reported during the study. Long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing bleeding in most pediatric patients with persistent or chronic ITP. Combined with future studies, these findings will help establish how eltrombopag should best be used in the management of pediatric patients with East Asian ancestry.

Evaluating the impact of thrombopoietin receptor agonist medications on patient outcomes and quality of life in paediatric immune thrombocytopenia through semi‐structured interviews

“…Outside of RCTs, a recent observational cohort study on eltrombopag in paediatric ITP patients reported 77% (89 of 116 patients) responded by meeting the platelet count criteria of ≥30 × 10 9 /L for six or more weeks in the absence of rescue therapy. 10 Similar to the RCTs, there were no significant side effects reported in this study.…”

“…This platelet count response is using the definition of response of platelet count criteria of ≥50 × 10 9 /L for six or more weeks in the absence of rescue therapy. Using a more liberal definition of response—defined as a platelet count ≥30 × 10 9 /L or at least doubling of the baseline platelet count, and absence of bleeding—the response rate (15/20 or 75%) was also similar to a recently published prospective observational cohort 10 …”

“…Side effects reported in these RCTs included headache, upper respiratory tract infection and diarrhoea as well as rise in liver enzymes, yet importantly there were no significant differences in serious adverse events between treatment and placebo groups. Outside of RCTs, a recent observational cohort study on eltrombopag in paediatric ITP patients reported 77% (89 of 116 patients) responded by meeting the platelet count criteria of ≥30 × 10 9 /L for six or more weeks in the absence of rescue therapy 10 . Similar to the RCTs, there were no significant side effects reported in this study.…”

“…Using a more liberal definition of response-defined as a platelet count ≥30 × 10 9 /L or at least doubling of the baseline platelet count, and absence of bleeding-the response rate (15/20 or 75%) was also similar to a recently published prospective observational cohort. 10 Qualitatively, results from the semi-structured interviews suggest an even higher percentage of patient response with 19/20 or 95% participants reporting that the medication is working. Improvements were also reported in sport/activity participation (11/20 participants) and child/youth mental health (11/20 participants).…”

Single Nucleotide Polymorphisms of the HIF1A Gene are Associated With Sensitivity of Glucocorticoid Treatment in Pediatric ITP Patients

“…In our center, we treated GT insensitivity patients with an escalating treatment strategy 47 and the long-term treatment with eltrombopag was generally safe, well tolerated, and effective in maintaining platelet counts and reducing the incidence of CITP in most pediatric patients with persistent ITP. 48 So, the specific SNP may not be associated with the development of CITP in this cohort. In addition, SNPs (STAT1, 1 TNFβ, 9 IL-17F, 12,13 SDF1, 10 and FCGRIIb 14 ) associated with development of CITP are different from SNPs (SIRT1, 15 SDF1, 10,16 ABCB1, 17 TNFα, 18 and IL-23R 19 ) associated corticosteroid sensitivity except SDF1.…”