Lusutrombopag, an oral thrombopoietin receptor agonist, was found to reduce the need for platelet transfusion in patients with chronic liver disease with a planned invasive procedure, according to results in an abstract of a phase III trial that will be presented as a latebreaker at the annual meeting of the American Association for the Study of Liver Disease in San Francisco.
The novel therapy, which upregulates platelet production, was “efficacious and well tolerated,” producing a reduced risk of overall adverse events, including bleeding events, according to Dr. Namiki Izumi, Musashino Red Cross Hospital, Tokyo.
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In this ongoing global phase III trial, called L-PLUS 2, 96 patients with chronic liver disease, a platelet count less than 50,000/microL, and a planned invasive procedure were randomized to receive a once-daily 3-mg tablet of lusutrombopag or a matching placebo for 7 days. The primary endpoint was the need for a preoperative platelet transfusion.
“The proportion of patients who required no preoperative platelet transfusion was significantly greater with lusutrombopag [29.2% vs. 12.5%; P less than .0001],” Dr. Izumi reported. The proportion of responders, defined by a platelet count greater than or equal to 50,000/microL and a greater than or equal to 20,000/microL-increase from baseline, was also significantly greater in the lusutrombopag arm (77.1% vs. 6.3%; P less than .0001).
In addition, the median time with a platelet count greater than or equal to 50,000/microL was 22.1 days in those who received lusutrombopag but no platelet transfusion versus 3.3 days in the placebo patients who did receive transfusion (P less than 0.0001).
Many adverse events occurred less frequently in the arm randomized to lusutrombopag. This included bleeding events (14.6% vs. 27.1%) and postoperative fever (39.6% vs. 56.3%). The rates of procedural hypertension (41.7% vs. 37.5%) and procedural pain (45.8% vs. 41.7%) were slightly greater in the group randomized to lusutrombopag, but elevations in liver enzymes, such as aspartate aminotransferase (22.9% vs. 31.3%) were somewhat lower.
“Protocol-required imaging revealed one thromboembolic event of the portal venous system in each study arm, neither of which was related to platelets,” according to Dr. Izumi, who reported that no patient discontinued therapy as a result of an adverse event.
Because of the frequency with which thrombocytopenia is observed in patients with chronic liver disease, platelet transfusion is considered a standard procedure when an invasive intervention is planned, according to Dr. Izumi. The data from this trial suggest that preoperative treatment with lusutrombopag may be an alternative.
Dr. Izumi reported financial relationships with Bayer, Daiichi Sankyo, Gilead, Merck, and Shionogi.