Avatrombopag: Beyond efficacy

Abstract INTRODUCTION Thrombopoietin Agonists (TPO-AR) are the treatment of choice in 2nd line in ITP. There are different agonists that act at different levels and with different modes of administration. Avatrombopag is a 2nd generation oral agonist that acts at level of transmembrane domain of TPO receptor. In Spain its prescription has progressively increased, similar to what has been observed in other countries (Tomassello et al1). On the other hand, Cooper2 claimed that avatrombopag dominated romiplostim (more effective and less expensive) and was cost-effective versus eltrombopag, with incremental cost-effectiveness ratio (ICER) of GBP £5982 per QALY in UK. OBJECTIVE Analysis of efficacy and efficiency of Avatrombopag in different treatment lines (from first-line to 3 or more lines) in management of ITP in a 3rd level center. MATERIAL AND METHODS Data collection from patients' electronic medical records: Variables include age, sex, type of ITP (Primary/Secondary), previous treatment lines and TPO agonists prior to Avatrombopag, reason for switch, platelet count pre, at one month, 3,6,9 and 12 months and dose at each of these times of different agonists and analysis of cost variation. Results are expressed in mean (and SD), median (and IQR), and percentage. For costs, the Spanish prizes of different agonists is taken as a reference () RESULTS 22 patients were included: 13 women (59.09%) and 9 men (40.91%). Mean age was 55.91 years (SD 20.9). 68.18% have a primary ITP. 1 patient received Ava in 1st line, 3 in 2nd line and remaining 18: 12 in 3rd line (54.55%), 2 in 4th line and 2 in 6th line (9.09%, respectively). 1 in 5th and another in 7th line. 45.45% came from previous Eltrombopag, 27.27% from Romiplostim and 9.09% from both agonists. Prior to switch, 36.36% of patients received concomitant medication for ITP (preferably Prednisone in doses < 5-10 mg/day). There are statistically significant differences in platelet counts throughout treatment with Avatrombopag (ANOVA, p 0.0018), with sustained increase in count (previous mean from 51000/ml to more than 140000/ml). It should be noted that the patient who received Ava in 1st line achieved complete remission and discontinued treatment. Weekly cost of treatment of 18 patients treated with agonists prior to switch was 12657.67 euros (703.2 euros/patient/week) (Graphs 1 and 2). After 3 months, reduction in costs is already noticeable: total weekly cost of 5886.34 euros, with average weekly cost per patient being 280.30 euros. After 12 months, this trend towards cost reduction is consolidated: total weekly cost of 5,808.41 euros and average cost per patient/weekof 264.02, implying cost reduction of 54.11% and 62.45% per patient, respectively. Difference is statistically significant (Student test, p < 001). With less than 50% of cost of previous treatment, 4 more patients were treated, with a reduction in the need for concomitant treatment (from 8 to 4 patients) without statistical significance (Chi-square, p 0.366). CONCLUSION Switch to Avatrombopag has been a clinical success both for its high efficacy - it improves platelet counts with less variability - and for its efficiency, due to significant reduction in costs (54.1%), allowing more patients to be treated at half the cost (reduction in weekly cost per patient of 62.45%), in line with Cooper's results2. In relation to reduction in concomitant treatment, although there is no statistical difference, this is probably due to small sample size since 50% of patients saw this need reduced. Reduction in total weekly and per-patient cost at 12 months is very statistically significant and highlights the favorable economic impact of switching to this “new” agonist. It would be interesting to evaluate this impact in a larger cohort of patients such as the one included in AVESPA study 1 Tomassello R et al, Real-World Use, Effectiveness and Safety of Romiplostim, Eltrombopag and Avatrombopag in Immune Thrombocytopenia: Data from the Norwegian ITP RegistryBlood (2023) 142 (Supplement 1): 3952. 2, Cooper et al, The Cost-Effectiveness of Avatrombopag Versus Eltrombopag and Romiplostim in the Treatment of Patients with Immune Thrombocytopenia in the UK, K. J. Mark. Access Health Policy 2025, 13, 11. https://doi.org/10.3390/jmahp 13020011 3. Pascual C. et al, Avespa Study: Effectiveness and Safety of Avatrombopag in Immune Thrombocytopenia (ITP). a Real-World Study of the Spanish ITP Group (GEPTI).Blood (2024)144, Supplement 1, 713