Avatrombopag ethnic sensitivity analysis in chronic liver disease and thrombocytopenia patients: individual-level pooled analysis

Abstract

Introduction: Few data have been published on the ethnic sensitivity of effectiveness, pharmacokinetics (PK), and pharmacodynamics (PD) of avatrombopag for the management of thrombocytopenia in patients with chronic liver disease (CLD). Methods: An ethnic sensitivity analysis was performed based on the results from two phase III studies (ADAPT-1 and ADAPT-2), with a primary endpoint of the proportion of patients without the requirement of platelet transfusion or rescue treatment for bleeding after randomization to 7 days following a scheduled procedure, and three phase I studies in healthy subjects. Cochran–Mantel–Haenszel and Fisher’s exact tests were used to compare the differences in effectiveness in different ethnicities and overall population. Results: In total, 435 patients (placebo, n = 158; avatrombopag, n = 277) were stratified into various ethnic groups: 121 East Asians, including the subgroup of 27 Chinese, and 259 Caucasians. The proportion of patients who did not receive a platelet transfusion and those with a platelet count ⩾50 × 10 9 /L in the avatrombopag 40 and 60 mg groups were higher than that of placebo for all ethnicities and in the overall population. Statistical significance was obtained in the overall population and for all ethnicities other than Chinese patients, a group with a very small sample size. No significant difference was observed in the proportion of responders in each ethnic group compared to overall population ( p > 0.05). The incidence of adverse events in East Asians was similar to that in both Caucasians and the overall population. Conclusion: Avatrombopag was effective and safe in the management of thrombocytopenia in Chinese patients with CLD. Ethnicity does not appear to influence the efficacy, safety, PK, or PD of avatrombopag.