PF709 TAPERING AND DISCONTINUATION OF THROMBOPOIETIN RECEPTOR AGONISTS IN ITP: EXPERT CONSENSUS OPINIONS
Authors: N. Cooper, R. Bird, T. Hato, D. Kuter, M. Lozano, M. Michel, U. Platzbecker, D. Provan, P. Scheinberg, Y. Tomiyama, R. Wong, J.B. Bussel
Journal: HemaSphere (2019)

Background: Immune thrombocytopenia (ITP) is an acquired autoimmune‐mediated disorder characterized by a platelet count &lt;100,000/μL and variable bleeding and fatigue. First‐line treatment is usually corticosteroids, which provide high response rates but are only recommended for short‐term use, due to toxicities associated with long‐term use. Thrombopoietin receptor agonists (TPO‐RAs), romiplostim and eltrombopag, are second‐line treatments that stimulate platelet production. Initially, it was thought that once a TPO‐RA was started, treatment would continue indefinitely. However, it became clear that certain patients can discontinue TPO‐RAs and maintain adequate platelet counts after stopping treatment. However, there is no clarity on how many and which patients might achieve sustained responses off treatment and which strategies are optimal to achieve these responses. Aims: To develop an expert physician‐led strategy for discontinuing TPO‐RA treatment in ITP patients. Methods: Twelve experts from the US, Brazil, Western Europe, Asia, and Australia responded to a specially designed questionnaire focusing on: selection of patients for tapering and discontinuation of TPO‐RA agents, optimal strategy to do so, monitoring approaches during and after discontinuation, and when and how to reinstate treatment if there was a relapse. Results: The respondents agreed that patients with persistent or chronic ITP receiving any dose of TPO‐RA could be considered for dose reduction in cases of stable response to treatment. Other factors should be considered, including a prior bleeding episode due to platelet count drop, hard‐to‐manage ITP or platelet count stable only on TPO‐RA treatment, patient's lifestyle, frequency and/or severity of infections that could alter counts, and time since diagnosis. Table 1 summarizes points of general panel agreement versus decisions dependent on physician preference. There was agreement on tapering rather than abrupt discontinuation; however, both faster and slower dose reductions were deemed appropriate depending on initial response to dose reduction. Half the experts would monitor platelet counts 14 days after dose reduction. The respondents were split between stable platelet counts of 50,000 or 100,000/μL, both to start tapering and to allow a second dose reduction, either immediately, or more often after a wait of 4–8 weeks. However, if the platelet count dropped to between 20,000 and 50,000/μL during tapering, treatment should be reinforced by use of the same TPO‐RA and potential addition of immunosuppression. In such a case, as platelet counts stabilize, a new tapering attempt is recommended after 2–3 months. During and after TPO‐RA discontinuation, platelet counts should be monitored regularly, and the intervals could increase in line with the duration of patient response. Initial monitoring frequency would be at 1–4‐week intervals and gradually increase to 3‐month intervals by the second half of the first year off treatment if an adequate count was maintained. Summary/Conclusion: All physicians supported the use of a tapering strategy for patients with a sustained and stable response after a minimum of several months of treatment with a TPO‐RA. Certain patients with very high platelet counts on a TPO‐RA are obvious candidates to discontinue treatment, but also those with stable counts of &gt;50,000/μL could be considered for tapering. image