Efficacy of Lusutrombopag for Thrombocytopenia in Patients with Chronic Liver Disease Scheduled to Undergo Invasive Procedures

Abstract

Objective Lusutrombopag is a thrombopoietin receptor agonist that improves thrombocytopenia in patients with chronic liver disease scheduled to undergo invasive procedures. However, information on the efficacy of repeated lusutrombopag treatment and factors associated with the treatment is scarce. We analyzed the efficacy of repeated lusutrombopag treatment and the factors associated with a response to lusutrombopag. Methods Thirty-nine patients with chronic liver disease who received lusutrombopag treatment before undergoing invasive procedures were enrolled in this retrospective study. Of the 39 patients, 10 received lusutrombopag treatment multiple times for a total of 53 regimens of lusutrombopag treatment. Changes in platelet counts, the effects of repeated lusutrombopag treatment, and factors associated with response to lusutrombopag were analyzed. Results The median platelet count increased significantly from 4.5×10 4 /μL before lusutrombopag treatment to 7.2×10 4 /μL before the invasive procedure (P<0.01), and patients undergoing 49 of the 53 (92%) treatment regimens succeeded in undergoing invasive procedures without needing platelet transfusions. In patients who received lusutrombopag treatment repeatedly, the median platelet count significantly increased following the second administration of lusutrombopag, and the effects of lusutrombopag were similar between the first and second administration. A multivariate analysis identified the absence of diabetes mellitus (odds ratio, 5.56 for presence; p=0.04) as a significant and independent predictor of a response to lusutrombopag. Conclusion Lusutrombopag treatment significantly increased platelet counts in patients with chronic liver disease, making it possible to receive invasive procedures. The treatment produced identical effects when it was repeated. The efficacy of lusutrombopag might be decreased in patients with diabetes mellitus.

Real-world use of avatrombopag in patients with chronic liver disease and thrombocytopenia undergoing a procedure

“…The TEAEs identified in this study were similar for all doses of avatrombopag taken and do not suggest any new or unexpected safety concerns compared to the 2 large, multicenter, phase 3 ADAPT studies. The safety and effectiveness profiles did not differ in the 2 patients who received 2 subsequent courses of treatment with avatrombopag for separate procedures, in line with data published for lusutrombopag, [28] and indicating that TPO-RAs are suitable for repeated use in this population.…”

“…www.md-journal.com period. Although direct comparisons cannot be made due to the heterogeneity of patient populations and study designs, the proportion of patients not requiring a platelet transfusion was higher than that in the phase 3 ADAPT studies, [21] higher than that reported for eltrombopag (72%), [23] and equivalent (97.5%) [24] or higher (65%-94%) [25][26][27][28] than that reported for lusutrombopag.…”

“…Forty-nine out of 50 enrolled patients did not require a platelet transfusion after the baseline visit and up to 7 days following procedure day (98%; 95% CI: 89.4%–99.9%), and no patients required a rescue procedure for bleeding during the study period. Although direct comparisons cannot be made due to the heterogeneity of patient populations and study designs, the proportion of patients not requiring a platelet transfusion was higher than that in the phase 3 ADAPT studies, [21] higher than that reported for eltrombopag (72%), [23] and equivalent (97.5%) [24] or higher (65%–94%) [25–28] than that reported for lusutrombopag.…”

“…The safety profile observed in this study is comparable to the pooled phase 3 ADAPT data and similar to the reported safety of lusutrombopag. [25,26,28] One of the 2 mild bleeding events was likely procedure-related and none were considered related to avatrombopag by the investigator. Importantly, no thromboembolic events were reported in any patient and no new safety signals were identified in this broader group of patients with CLD, such as patients with a platelet count ≥ 50 × 10 9 /L and patients receiving concomitant medications that were prohibited in the ADAPT studies.…”

A single course of lusutrombopag for multiple invasive procedures in cirrhosis-associated thrombocytopenia: A case series

“…[11] In addition, comorbidities seem to influence the response rate to lusutrombopag therapy. Nishida et al [12] identified the presence of diabetes as a negative predictor of response to lusutrombopag, while Takeuchi et al [13] noticed that renal function parameters (blood urea nitrogen, creatinine, glomerular filtration rate) were significantly and negatively associated with platelet count. Finally, the post hoc analysis of L-PLUS 1 and L-PLUS 2 trials by Tanaka et al [14] revealed that baseline leukocyte count below the normal range is associated with smaller platelet count increases after lusutrombopag treatment than patients with leukocyte count within the normal range.…”