Relationship between baseline clinical characteristics and efficacy of lusutrombopag in thrombocytopenic patients with chronic liver disease: post hoc analysis of two placebo-controlled phase 3 trials

Objective Lusutrombopag is a thrombopoietin receptor agonist approved to treat thrombocytopenia in patients with chronic liver disease (CLD). This post hoc analysis of the Japanese L-PLUS 1 and global L-PLUS 2 trials aimed to clarify factors related to platelet count increase after lusutrombopag treatment. Methods In L-PLUS 1, Pearson's correlation coefficients were used to evaluate correlations between platelet count and spleen index, thrombopoietin concentration, white blood cell (WBC) counts, and red blood cell counts (intent-to-treat [ITT] population). Associations between platelet count increase after lusutrombopag treatment and each parameter were assessed by regression analysis and mixed-effect model for repeated measures (MMRM). Associations between time-dependent changes in platelet count increase and each parameter were also examined in the L-PLUS 2 lusutrombopag ITT population by MMRM. Results In L-PLUS 1, the baseline platelet count was correlated with pretreatment spleen index (r = -0.23, 95% confidence interval [CI] -0.41 to -0.03) and WBC count (r = 0.26, 95% CI 0.06 to 0.43). No selected parameters were associated with the maximum platelet count increase from baseline. Patients with WBC counts below the normal range showed smaller platelet count increases after lusutrombopag treatment than patients with WBC counts within the normal range (p = .0028). In L-PLUS 2 (p = .0533), findings were similar and confirmed by larger pooled data of L-PLUS 1/L-PLUS 2 (p = .0021). Conclusions This post hoc analysis revealed a possible association between baseline WBC count and platelet count increase after lusutrombopag treatment. WBC count could be a relevant factor for lusutrombopag efficacy.