Options for Tapering TPO-RA in ITP Patients: Practical Experience and Expert Consensus
A recently published British study aims to provide recommendations on tapering TPO-RA in patients with immune thrombocytopenia (ITP) based on existing evidence, survey results of clinical practice among hematologists, and expert consensus.
TPO-RA in the Treatment of ITP
Immune thrombocytopenia is an autoimmune disease characterized by decreased production of blood platelets and their increased destruction. Both blood platelets and their precursors, megakaryocytes, are targets of autoantibodies. In the 21st century, thrombopoietin receptor agonists (TPO-RA) that induce the proliferation and differentiation of megakaryocytes and increase platelet production have gained a crucial role in possible treatments. TPO-RAs can improve platelet counts and reduce the risk of severe bleeding in 80-90% of ITP patients, significantly enhancing their quality of life. Long-term response rates in studies range between 65 and 88%, and the tolerance of these medications is very good.
Options for Reducing or Stopping Therapy
The primary goal of TPO-RA treatment is not to normalize platelet counts but to increase them to reduce the risk of bleeding, which is well-observed when platelet counts rise above 50 × 109/L. Many patients require continuous long-term administration of TPO-RA to maintain adequate platelet levels. However, for some patients, sustained responses can be achieved after dose reduction or even discontinuation of TPO-RA. Approaches to tapering TPO-RA vary, and there is no clear recommendation available.
Survey Results and Expert Consensus
A survey among British hematologists revealed that an estimated 30-34% of their patients were able to undergo dose reduction or discontinuation, and 29-35% of these patients did not require restarting treatment after an average therapy-free period of 86-106 days. No clear indicators were identified to predict sustained patient responses to treatment or responses to TPO-RA dose reduction or discontinuation.
Experts concluded that for approximately 30% of patients, it is appropriate to consider tapering or stopping TPO-RA, which can occur after 6-12 months of treatment with an adequate response—achieving a platelet count > 50 × 109/L in ≥ 75% of measurements over the previous 6 months. Treatment resumption may be considered if platelet counts drop or if the patient's disease symptoms reappear. Individual factors and variations must also be taken into account when deciding on dose reduction or discontinuation of TPO-RA.
Conclusion
The survey results and expert consensus agree that dose reduction or discontinuation of TPO-RA therapy is possible for some ITP patients. Future studies should focus on better predicting which patients are more likely to achieve a sustained response even with dose reduction or discontinuation of this modern and effective therapy.
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Source: Cooper N., Hill Q. A., Grainger J. et al. Tapering and discontinuation of thrombopoietin receptor agonist therapy in patients with immune thrombocytopenia: results from a modified Delphi panel. Acta Haematol 2021 Mar 31; 144 (4): 418–426, doi: 10.1159/000510676.
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