Treatment of Immune Thrombocytopenia: Choice of TPO Mimetics in Clinical Practice

Introduction

Primary immune thrombocytopenia (ITP) is a rare disease characterized by an immune-mediated decrease in platelet count due to increased destruction and impaired production and maturation of megakaryocytes in the bone marrow. The last decade has seen significant changes in the management of ITP, also considering the availability of thrombopoietin receptor agonists (TPO-RAs). These agents increase platelet counts by activating the c-mpl receptor and supporting the survival, proliferation, and differentiation of megakaryocytes.

TPO-RAs, such as romiplostim and eltrombopag, belong to the second line of ITP treatment. Currently, the choice of the specific agent depends mainly on the physician's experience and patient preference, as clear evidence-based recommendations are generally lacking. Predictive factors for response to TPO-RAs are also not well known, apart from early initiation of their application or a noticeable increase in platelet counts at the start of treatment.

Real-world Data

Study Objectives

An observational study published in December 2019 evaluated data from monitoring adult patients who began using TPO-RAs between January 2012 and December 2014. The objective was to analyze how TPO-RAs are managed in real clinical practice (regarding treatment indication, safety, and potential switch to another TPO-RA) and to understand possible patient characteristics that lead to a preference for one agent over another.

Study Population

The study included 121 patients. At the start of TPO-RA treatment, 67.8% had chronic ITP with a median time from diagnosis of 65.6 months, 15.7% had persistent ITP, and 16.5% had newly diagnosed ITP.

Key Findings

Overall, 32.2% of patients switched TPO-RAs, with a trend toward more frequent changes in patients initially treated with eltrombopag. Reasons for switching included insufficient efficacy (especially in those treated with eltrombopag), patient or physician preference, adverse effects, and others.

Data showed that a platelet count ≤ 25 × 10⁹/l at the start of TPO-RA treatment was associated with a 2.8× higher probability of being prescribed romiplostim compared to eltrombopag (p = 0.010). Administering romiplostim as the first-choice TPO-RA without subsequent switching to eltrombopag was associated with a 50% probability of achieving a therapy-free response (TFR) after 2.9 years of treatment (3.3 years for chronic ITP). Romiplostim as the first-line TPO-RA was linked with a 3× higher probability of achieving TFR (p = 0.011), while switching TPO-RAs was associated with an 8.8× risk of not achieving TFR (p = 0.004).

Conclusion

This study provides an additional long-term perspective on the use of TPO-RAs in real clinical practice. More than a quarter of patients managed to achieve a stable response without further therapy after discontinuing TPO-RAs, with this outcome appearing more commonly when romiplostim was used as the first-choice agent within this drug group.

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Source: Lozano M. L., Mingot-Catellano M. E., Perera M. M. et al. Deciphering predictive factors for choice of thrombopoietin receptor agonist, treatment-free responses, and thrombotic events in immune thrombocytopenia. Sci Rep 2019 Nov 13; 9 (1): 16680, doi: 10.1038/s41598-019-53209-y.