PF700 REAL‐WORLD DATA DEMONSTRATE SAFETY AND EFFECTIVENESS OF LUSUTROMBOPAG IN CHRONIC LIVER DISEASE PATIENTS WITH THROMBOCYTOPENIA UNDERGOING PLANNED INVASIVE PROCEDURES: INTERIM ANALYSIS

Abstract

Background:Lusutrombopag is a thrombopoietin receptor agonist developed by Shionogi & Co., Ltd. It is approved in Japan and US for improvement of thrombocytopenia, and in EU for patients with severe thrombocytopenia, associated with chronic liver disease scheduled to undergo invasive procedures. Postmarketing surveillance (October 2016‐May 2021) of safety and effectiveness data is ongoing in Japanese clinics.Aims:Data from 338 patients as of September 2018, including 21 re–treated patients, were analyzed for this interim report.Methods:Postmarketing surveillance plans to enroll 1,000 patients and follow them for 2 months after initial lusutrombopag dose. Patients receiving ≥1 re‐treatment within 6 months of initial treatment are observed for 2 months from start of each re‐treatment. This study captures data on adverse events occurring during and after treatment. Primary effectiveness outcome is proportion of patients who do not require pre‐operative platelet transfusion.Results:A total of 334 patients were evaluable for safety (4 excluded: registration violations [n = 2]; overlapping patients [n = 2]) and 318 for effectiveness (16 excluded: off‐label use [n = 1]; off‐indicated dosage/administration [n = 1]; use in unapproved population [Child‐Pugh C; n = 14]). Most patients had liver cirrhosis (315/334, 94%). Mean baseline platelet count ± SD was 46 ± 14x109/L (range 15–110; n = 315). There were 380 procedures in 334 patients, including 110/380 (28.9%) radiofrequency ablation, 59/380 (15.5%) transarterial chemoembolization, and 49/380 (12.9%) endoscopic injection sclerotherapy. Fourteen adverse drug reactions, including portal vein thrombosis (n = 4), increased alanine aminotransferase (n = 2), and increased aspartate aminotransferase (n = 2), were reported in 11/334 patients (3.3%). Forty‐one serious adverse events occurred in 29/334 patients (8.7%), including hepatic failure (n = 3; 0.9%), hepatic encephalopathy (n = 2; 0.6%), ascites (n = 2; 0.6%), and thrombosis (n = 1 splenic vein, 0.3%; n = 6 portal vein thrombosis, 1.8%); 7 events were considered treatment‐related. Mean time to procedure after starting lusutrombopag was 12.4 days. Two hundred eighty‐two (93%) of 303 patients without platelet transfusion refractoriness underwent procedure without platelet transfusion. After lusutrombopag, mean maximum platelet count was 89 ± 35x109/L (range 25–352; n = 288); mean maximum change from baseline platelet count was 42 ± 31x109/L (range −6–276; n = 288). In 21 re‐treated patients, no adverse drug reactions were reported during the observational period; platelet transfusion avoidance rate was 100%.Summary/Conclusion:Use of lusutrombopag in real‐world clinical practice demonstrates the product is safe and effective for patients with thrombocytopenia associated with chronic liver disease undergoing planned invasive procedures (consistent with previously reported clinical trial data).