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Tapering and discontinuation of thrombopoietin receptor agonists in immune thrombocytopenia: Real-world recommendations

Published on May 1, 2020in Blood Reviews6.125
· DOI :10.1016/J.BLRE.2019.100647
F. Zaja (DSM), Monica Carpenedo9
Estimated H-index: 9
+ 8 AuthorsPotito Rosario Scalzulli17
Estimated H-index: 17
(Casa Sollievo della Sofferenza)
Abstract
Abstract Thrombopoietin receptor agonists (TPO-RAs) are currently indicated for continuous treatment of chronic primary immune thrombocytopenia (ITP). However, there is growing evidence that TPO-RAs can also trigger sustained response in 10–30% of cases after treatment tapering and discontinuation. Therefore, at least for selected responding patients, it might be rational to plan TPO-RA interruption to exploit off-treatment response. Intriguingly, complete or partial responses with TPO-RAs are frequently observed when treatments are initiated early, suggesting that unknown immune-related mechanisms may be involved in this phenomenon. The sustained responses observed after interruption of TPO-RAs may be interpreted as a recovery of immunological tolerance; thus, the re-establishment of immunological equilibrium might be primarily responsible for the observed off-treatment effect. Importantly, these findings may indicate that anticipated TPO-RA usage can lead to improved responses, and that optimized tapering and interruption in selected patients can furthermore improve prognoses. On the base of this rationale, a series of real-life considerations have been generated by a panel of Experts to elucidate possible novel criteria and modalities to identify subgroups of patients who can benefit from tapering and/or discontinuation of TPO-RAs. Towards this aim, the results of a survey of ITP experts are herein reported, reflecting a snapshot of current real-life experience on early discontinuation of TPO-RA-based therapy. The present manuscript also highlights the importance of future translational studies on novel prognostic and predictive biomarkers that can stratify patients and facilitate the clinical choice for second-line treatment of ITP.
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#1Jan-Paul Bohn (Innsbruck Medical University)H-Index: 3
#2Michael Steurer (Innsbruck Medical University)H-Index: 20
Immune thrombocytopenia (ITP) is an acquired autoimmune phenomenon resulting in low platelet count and increased bleeding risk. Goals of upfront management include prompt control of severe bleeding—which is rare—as well as induction and maintenance of a hemostatic platelet count. Thus, optimal management of ITP patients is often challenging and requires a highly individualized approach. Many patients may not suffer significant bleeding despite severe thrombocytopenia and the risk of toxicity ass...
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In phase 2/3 trials, eltrombopag treatment of 6 months or less in patients with chronic/persistent immune thrombocytopenia (ITP) increased platelet counts and reduced bleeding. The open-label EXTEND study evaluated long-term safety and efficacy of eltrombopag in adults with ITP who had completed a previous eltrombopag study. For the 302 patients enrolled, median duration of eltrombopag treatment was 2.37 years (2 days-8.76 years). Median platelet counts increased to 50 × 10 9 /L or more by week ...
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