Evaluation of the Efficacy of Lusutrombopag for Chronic Liver Disease Based on Pre-Treatment Platelet Counts: A Retrospective Multicenter Study

Abstract

Background: Oral thrombopoietin receptor agonists are used to treat thrombocytopenia in patients with chronic liver disease who are scheduled for invasive procedures. The efficacy of lusutrombopag based on the pretreatment platelet count was investigated.

Methods: Patients treated at nine hospitals from December 2015 to December 2023 were included. Efficacy was assessed by comparing the proportion of patients achieving a platelet count ≥ 50 000/μL and the change in platelet count.

Results: Seventy patients were eligible for evaluation. Patients with a pretreatment platelet count < 40 000/μL had a significantly lower rate of achieving a platelet count of ≥ 50 000/μL than those with a pretreatment count of 40 000-50 000/μL (62.5% vs. 84.2%, p = 0.038); however, there was no significant difference in the change in platelet count (25 700 vs. 24 400/μL, p = 0.972). Patients with viral-related cirrhosis showed a significantly greater change in platelet count than the others (29 100 vs. 19 200/μL, p = 0.012). For patients receiving multiple lusutrombopag treatments, the change in platelet count was significantly lower in the second treatment than in the first treatment (26 900 vs. 20 800/μL, p = 0.041). The main adverse event observed was thrombosis (2.9%).

Discussion: Lusutrombopag increases platelet count regardless of pretreatment levels, but efficacy, defined as achieving a platelet count of ≥ 50 000/μL, may be insufficient in patients with a pretreatment platelet count < 40 000/μL. Additionally, patients with non-viral liver disease responded less well to treatment compared to those with viral liver disease. Therefore, treatment strategies should be tailored based on pretreatment platelet counts and the etiology of liver disease.

Keywords: chronic liver disease; lusutrombopag; thrombocytopenia.

FIGURE 1

Patient screening and group classification based on baseline platelet counts (PLT). This flowchart illustrates the screening process for patients considered for inclusion in this study. Initially, 110 patients were included in the study. Exclusions were made for cases with significant data loss and baseline platelet count (PLT) ≥ 50 000/μL, totaling 40 patients. The remaining patients were categorized based on their baseline PLT: 38 patients with a higher baseline PLT (40 000 to < 50 000/μL) and 32 patients with a lower baseline PLT (< 40 000/μL).

FIGURE 2

Efficacy of lusutrombopag in patients with different baseline platelet levels (PLT). (A) Proportion of patients who did not require platelet transfusion on the day of invasive procedures. (B) Proportion of patients achieving platelet counts ≥ 50 000/μL on the day of the invasive procedure. (C) Magnitude of change in platelet count from baseline on the day of the invasive procedure. (D) Platelet counts at various time points (days 1, 5, 8–13, and 15–27). Data are the mean ± SD.

FIGURE 3

Comparative analysis of lusutrombopag efficacy in patients classified by liver disease etiology. (A) Proportion of patients who did not require platelet transfusion on the day of invasive procedures in the viral and non‐viral patient groups. (B) Proportion of patients achieving platelet counts ≥ 50 000/μL on the day of the invasive procedure in the viral and non‐viral patient groups. (C) Magnitude of change in platelet count from baseline on the day of the invasive procedure in the viral and non‐viral patient groups. (D) Platelet counts at various time points (days 1, 5, 8–13, and 15–27) in the viral and non‐viral patient groups. Data are the mean ± SD.

FIGURE 4

Analysis of the efficacy of multiple doses of lusutrombopag in patients with viral and non‐viral liver diseases. (A) Overall change in platelet count from baseline on the day of the invasive procedure at the first and second doses. (B) Platelet counts at various time points (days 1, 5, 8–13, and 15–27) after the first and second doses. (C) Subgroup analysis of changes in platelet count from baseline on the day of the invasive procedure with the first and second doses in patients with viral liver disease. (D) Platelet counts at various time points (days 1, 5, 8–13, and 15–27) after the first and second doses in patients with viral liver disease. (E) Subgroup analysis of changes in platelet count from baseline on the day of the invasive procedure with the first and second doses in patients with non‐viral liver disease. (F) Platelet counts at various time points (days 1, 5, 8–13, and 15–27) after the first and second doses in patients with non‐viral liver disease. Data are the mean ± SD.