A paper, titled “Lusutrombopag for thrombocytopenia in Chinese patients with chronic liver disease undergoing invasive procedures” was published recently on Hepatology International （IF=9.029）. It is completed by Prof. Jian Zhou and his team from the Department of Liver Surgery and Transplantation, Liver Cancer Institute of Zhongshan Hospital, Fudan University cooperating with other authors from nine Hepatology Research Centers.
This study focused on Chinese patients, which providing the latest evidence for the efficacy and safety of Lusutrombopag in Chinese patients with chronic liver disease thrombocytopenia. This study was a multicenter, randomized, double-blind, placebo-controlled, phase III study, to estimate the efficacy and safety of lusutrombopag for the treatment of severe thrombocytopenia (PLT < 50 × 109/L) in chronic liver disease patients who plan to undergo elective invasive procedures in the Chinese population.
In this study，66 patients with CLD and severe thrombocytopenia were randomized 2:1 to lusutrombopag or placebo arm treatment regimens for seven days one tablet a day (3 mg of lusutrombopag or placebo). And PLT was evaluated on Day 8 (the day after 7-day treatment) for primary endpoint analysis. The planned procedure that was invasive was performed between days 9 and 15. If the PLT was < 50× 109/L, preprocedural platelet transfusion was allowed.
The results of this study indicated that: Lusutrombopag was effective in raising PLT, diminishing platelet transfusion requirement. The proportion of responders (patients with PLT ≥ 50 × 109/L documenting an increase of ≥ 20 × 109/L from baseline and not received rescue therapy for bleeding) on Day 8 was evidently higher in the lusutrombopag group versus placebo (43.2% vs. 4.5%, p = 0.0011). And 72.7% of patients in the lusutrombopag group with PLT ≥ 50 × 109/L on or after Day 8 and within 2 days before procedure，which was the alternative criteria for not requiring platelet transfusion, while 18.2% in the placebo group. The median maximum PLT in lusutrombopag group increased to 80.5× 109/L, and the median time to reach maximum was 14.5 days. And in the placebo group the median maximum PLT and the median time to reach the maximum PLT were 60.0 × 109/L and 27.0 days, respectively. Two patients in the placebo group received platelet transfusion due to PLT < 50× 109/L before procedure, while no patient in the lusutrombopag group.
In safety, the overall incidence of TEAEs was similar in the lusutrombopag and placebo groups（84.1% vs. 90.9%）. And most of the TEAEs were mild or moderate in severity. No patients discontinued or died the study drug because of AEs in the lusutrombopag group. Compared with the placebo, the lusutrombopag group had a lower incidence of bleeding events (6.8% vs. 13.6%), and only one patient had thrombotic-related AE, which was brachiocephalic vein thrombosis, and was considered mild and not related to the study drug. Overall, lusutrombopag is a safe choice for such patients with CLD and thrombocytopenia in China, and the safety profile of lusutrombopag was similar to placebo.
Edding Group concluded an agreement with Shionogi & Co., Ltd.in June 2019 to license-in Lusutrombopag, a thrombopoietin receptor agonist (brand name in Japan: Mulpleta®，brand name in China：稳可达® ). The Phase III Study in Mainland China has achieved a positive result and the applications for drug approval of lusutrombopag have been officially accepted by NMPA in 2021.
About Chronic Liver Disease (CLD)
Chronic liver disease, especially viral hepatitis, is an important public health problem in China. According to the data released by the Chinese Center for Disease Control and Prevention(CDC), the number of cases of viral hepatitis in Class B notifiable infectious diseases in 2020 ranked first (1,138,781), and the incidence ranked first, about 81/ 100,000[1].
CLD mainly refers to the general term for liver diseases with liver cell necrosis and slowed liver regeneration as pathological manifestations. Thrombocytopenia is a common complication in patients with CLD. According to reports, up to about 70% of patients have varying degrees of thrombocytopenia, and about 14% are complicated with severe thrombocytopenia[2].
About Thrombocytopenia （TCP）
The degree of thrombocytopenia is related to the severity of liver disease. The more severe the liver disease, the more severe the thrombocytopenia. Thrombocytopenia increases the risk of clinically significant bleeding, such as cerebral or other internal bleeding, as well as petechiae, purpura, and mucosal hemorrhage. Nowadays, there are about 460,000 people in China suffer from chronic liver disease and require elective surgery[3].
In addition, thrombocytopenia not only refers to a condition in which the number of circulating platelets in the blood is lower than the normal number, but also includes diseases in which platelets cannot function normally, mainly including idiopathic thrombocytopenic purpura (ITP), adult patients with CLD, treatment of chemotherapy-induced thrombocytopenia (CIT), thrombotic thrombocytopenic purpura, acquired thrombocytopenia, etc.
About Mulpleta®
Mulpleta® (Lusutrombopag), which has already been approved for routine use in the US, EU, and Japan, is an orally active, small molecule agonist of the human thrombopoietin receptor that triggers the production of endogenous platelets. Mulpleta® is the latest generation of oral small-molecule TPO receptor agonists. Compared with the first generation, it is safer, convenient to use, and non-immunogenic and stable efficacy, providing patients with better medical options. By acting on the transmembrane domain of the human TPO receptors, Lusutrombopag activates the signal transduction pathway in the same manner as endogenous TPO to promote the production of platelets.
參考文獻：
1. 2020年全國法定傳染病疫情概況http://www.nhc.gov.cn/jkj/s3578/202103/f1a448b7df7d4760976fea6d55834966.shtml
2. Afdhal N, McHutchison J, Brown R, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008;48(6):1000–7.
3. 文獻檢索，弗若斯特沙利文分析