Risk of thrombosis in adults with primary immune thrombocytopenia treated with eltrombopag versus romiplostim: a target trial emulation in the French Adult Immune Thrombocytopenia (FAITH) Cohort.

BACKGROUND: Thrombopoietin receptor agonists (TPO-RAs) have been identified as a risk factor for thrombosis in immune thrombocytopenia (ITP). The possibility of a risk difference between eltrombopag and romiplostim (the only TPO-RAs available in France) is not known, and may exist due to pharmacological differences. OBJECTIVES: We aimed to compare the risk of thrombosis between eltrombopag and romiplostim among adult patients treated for primary ITP. METHODS: We performed a target trial emulation in the French national healthcare database. Patients exposed to a first line of TPO-RA were followed until the first hospitalization for thrombosis, TPO-RA discontinuation, death or end of follow-up after 1 year. We used Inverse Probability of Treatment Weighting, and conducted Cox proportional hazard models with time-varying adjustment. RESULTS: Between 2011 and 2022, 2,761 and 949 patients were included in the eltrombopag and romiplostim groups, respectively. Patients in the romiplostim group were older and had more risk factors for thrombosis. The 1-year, weighted cumulative incidence of thrombosis was 5.1% (95% CI: 3.6-6.6) for eltrombopag and 1.9% (95% CI: 1.0-2.7) for romiplostim. The adjusted Hazard Ratio for eltrombopag versus romiplostim was 1.93 (95% CI: 1.11-3.34) at 1 year. No significant difference was observed in the first 6 months, but emerged thereafter due to a few events. Results were similar for venous and arterial thrombosis considered separately. The risk difference was the widest in patients aged 75+ years. CONCLUSION: Eltrombopag was associated with a greater risk of thrombosis than romiplostim after 6 months of exposure and particularly in elderly patients.