Tapering and Discontinuation of Thrombopoietin Receptor Agonist Therapy in Patients with Immune Thrombocytopenia: Results from a Modified Delphi Panel.

Recent evidence suggests that in patients with immune thrombocytopenia (ITP) with a stable response on thrombopoietin receptor agonists, treatment may be tapered and/or discontinued. The objective of this study was to provide a guide for tapering and discontinuation of TPO-RA therapy in patients with ITP, based on hematologist survey results, existing evidence, and expert consensus. UK hematologists completed a survey to characterize self-reported practice patterns related to TPO-RA tapering and discontinuation in patients with ITP. Using a modified Delphi panel approach, ITP experts developed consensus statements regarding the use of TPO-RA tapering and discontinuation. Survey respondents estimated that 30-34% of their patients were suitable for tapering or discontinuation and that 29-35% of these patients required treatment re-initiation after an average treatment-free interval of 86-106 days. No clear predictors of patient suitability or response to tapering or discontinuation were identified. The ITP expert consensus was that approximately 30% of patients are eligible for tapering and discontinuation, which may be considered after 6-12 months for patients demonstrating an adequate treatment response (platelet count >50,000/µL at ≥75% of assessments in the preceding 6 months). Treatment re-initiation may be considered if the platelet count decreases or if the patient becomes symptomatic. Individual differences need to be taken into account when considering TPO-RA tapering or discontinuation. Tapering and discontinuation of TPO-RA therapy may be considered for certain patients with ITP. Further study is needed to better predict patients likely to achieve sustained off-treatment responses after tapering and discontinuation.

Cooper N ，Hill QA ，Grainger J ，Westwood JP ，Bradbury C ，Provan D ，Thachil J ，Ramscar N ，Roy A ... -  《-》

European Delphi panel to build consensus on tapering and discontinuing thrombopoietin receptor agonists in immune thrombocytopenia.

Barlassina A ，González-López TJ ，Cooper N ，Zaja F ... -  《-》

Tapering and Sustained Remission of Thrombopoietin Receptor Agonists (TPO-RAs): Is it Time for Paediatric ITP?

Thrombopoietin receptor agonists (TPO-Ras; romiplostim/eltrombopag/avatrombopag) have demonstrated high efficacy rates (59-88%) and a good safety profile in clinical trials with adult patients with immune thrombocytopenia (ITP). Similar efficacy and safety results have been observed with romiplostim and eltrombopag in paediatric cohorts. Continuous treatment with TPO-RAs has shown durable responses with long-term use, up to 3 years. The effect of TPO-RAs was generally considered transient, as platelet counts tended to drop to baseline values after a short period of time (about 2 weeks), unless treatment was maintained. Several groups have reported successful discontinuation of TPO-RAs without the need for concomitant treatments. This is referred to as sustained remission off treatment (SROT). Both short- and medium-term treatment with TPO-RAs may reduce costs to our healthcare systems and, more importantly, may reduce the potential side effects that may be associated with continuous TPO-RA treatment. The issue of tapering and discontinuation of TPO-RAs in paediatric patients with ITP has received little attention to date. Given that paediatric ITP has much higher rates of spontaneous remission than ITP in adults, we consider that the possibility of SROT of TPO-RAs in paediatric patients with ITP is a neglected but very relevant issue in this subtype of the disease.

Marcos-Peña S ，Fernández-Pernia B ，Provan D ，González-López TJ ... -  《-》

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) ... -  《-》

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 ... -  《-》