Thrombopoietin Receptor Agonists in Children with Immune Thrombocytopenia: A New Therapeutic Era.

Immune thrombocytopenia (ITP) is a common bleeding disorder in childhood. The management of ITP in children is controversial, requiring personalized assessment of patients and therapeutic choices. Thrombopoietin receptor agonists (TPO-RAs), eltrombopag and romiplostim, have been shown to be safe and effective for the treatment of pediatric ITP. The aim of our research is to define the role of thrombopoietin receptor agonists in the management of pediatric ITP. This review focuses on the use of TPO-RAs in pediatric ITP, in randomized trials and in clinical routine, highlighting their key role in the management of the disease. Eltrombopag and romiplostim appear effective treatment options for children with ITP. Several clinical studies have assessed that the use of TPO-RAs increases platelet count, decreases bleeding symptoms and improves health-related quality of life. Moreover, TPO-RAs are well tolerated with minor side effects. Although long term efficacy and safety of TPO-RAs still require further investigations, their use is gradually expanding in the clinical practice of children with ITP.

Lassandro G ，Palladino V ，Vecchio GCD ，Palmieri VV ，Corallo PC ，Faienza MF ，Giordano P ... -  《-》

Thrombopoietin Receptor Agonist Use in Children: Data From the Pediatric ITP Consortium of North America ICON2 Study.

Data on second-line treatment options for pediatric patients with immune thrombocytopenia (ITP) are limited. Thrombopoietin receptor agonists (TPO-RA) provide a nonimmunosuppressive option for children who require an increased platelet count. We performed a multicenter retrospective study of pediatric ITP patients followed at ITP Consortium of North America (ICON) sites to characterize TPO-RA use. Seventy-nine children had a total of 87 treatments (28 eltrombopag, 43 romiplostim, and eight trialed on both). The majority had primary ITP (82%) and most (60.8%) had chronic ITP. However, 22% had persistent ITP and 18% had newly diagnosed ITP. During the first 3 months of treatment, 89% achieved a platelet count ≥ 50 × 10(9) /l (86% romiplostim, 81% eltrombopag, P = 0.26) at least once in the absence of rescue therapy. The average time to a response was 6.4 weeks for romiplostim and 7.0 weeks for eltrombopag (P = 0.83). Only 40% of patients demonstrated a stable response with consistent dosing over time. An intermittent response with constant dose titration was seen in 15%, and an initial response that waned to no response was seen in 13%. Significant adverse events were minimal with the exception of two patients with thrombotic events and one who developed a neutralizing antibody. Our results demonstrate that TPO-RA agents are being used in children with ITP of varying duration and severity. The response was similar to clinical trials, but the sustainability of response varied. Future studies need to focus on the ideal timing and rationale for these medications in pediatric patients.

Neunert C ，Despotovic J ，Haley K ，Lambert MP ，Nottage K ，Shimano K ，Bennett C ，Klaassen R ，Stine K ，Thompson A ，Pastore Y ，Brown T ，Forbes PW ，Grace RF ，Pediatric ITP Consortium of North America (ICON) ... -  《-》

Thrombopoietin-receptor agonists for children with immune thrombocytopenia: a systematic review.

Zhang J ，Liang Y ，Ai Y ，Xie J ，Li Y ，Zheng W ... -  《-》

Thrombopoietin Receptor Agonists in the Treatment of Chronic Resistant Primary Immune Thrombocytopenia: Efficacy and Safety Data in Real Clinical Practice.

Ptushkin VV ，Vinogradova OY ，Pankrashkina MM ，Chernikov MV ，Arshanskaya EG ，Tkachenko NE ... -  《TERAPEVTICHESKII ARKHIV》

Real-world use of thrombopoietin receptor agonists for the management of immune thrombocytopenia in adult patients in the United Kingdom: Results from the TRAIT study.

Few studies have reported the real-world use of both romiplostim and eltrombopag in immune thrombocytopenia (ITP). TRAIT was a retrospective observational study aimed to evaluate the platelet responses and adverse effects associated with the use of these thrombopoietin receptor agonists (TPO-RAs) in adult patients with ITP in the United Kingdom. Of 267 patients (median age at diagnosis, 48 years) with ITP (primary ITP [n = 218], secondary ITP [n = 49]) included in the study, 112 (42%) received eltrombopag and 155 (58%) received romiplostim as the first prescribed TPO-RA. A platelet count ≥30 × 109/L was achieved in 89% of patients with the first TPO-RA treatments, while 68% achieved a platelet count ≥100 × 109/L. Treatment-free response (TFR; platelet count ≥30 × 109/L, 3 months after discontinuing treatment) was achieved by 18% of the total patients. Overall, 61 patients (23%) switched TPO-RAs, most of whom achieved platelet counts ≥30 × 109/L with the second TPO-RA (23/25 who switched from eltrombopag to romiplostim [92%]; 28/36 who switched from romiplostim to eltrombopag [78%]). TFR was associated with secondary ITP, early TPO-RA initiation after diagnosis, the presence of comorbidity and no prior splenectomy or treatment with steroids or mycophenolate mofetil. Both TPO-RAs had similar efficacy and safety profiles to those reported in clinical studies.

Cooper N ，Scully M ，Percy C ，Nicolson PLR ，Lowe G ，Bagot CN ，Thachil J ，Grech H ，Nokes T ，Hill QA ，Bradbury C ，Talks K ，Dutt T ，Evans G ，Pavord S ，Wexler S ，Charania A ，Collington SJ ，Ervin A ，Ramscar N ，Provan D ... -  《-》