Discussion
thrombosis, hepatitis B, TPO-RAs, thrombocytopenia, liver disease, liver cirrhosis, B liver disease, hepatitis C, CLD, thrombosis-related
THROMBOSIS, HEPATITIS B, THROMBOCYTOPENIA, LIVER DISEASE, LIVER CIRRHOSIS, HEPATITIS C, VEIN THROMBOSIS, CLD
This phase 3 study showed that the effect of lusutrombopag (3 mg, for seven days consecutive, and once daily) was more significant than that of placebo in raising PLT and diminishing platelet transfusion requirement in adult patients of China with severe thrombocytopenia and CLD being treated by invasive elective procedures. Further, its safety profile was on the similar lines as the placebo, with no increase in the risk of thrombosis-related AEs. The overall results of the study conducted in China are consistent with the previous studies L-PLUS 1 and 2 [L-PLUS 1 was a randomized, double-blind, placebo-controlled phase 3 clinical trial, which showed that the proportion of patients in lusutrombopag group agrees with the primary endpoint (no pre-procedure requirement of platelet transfusions) is significantly higher than that in placebo group (79.2% [38/48] vs. 12.5% [6/48], Furthermore, the proportion of patients with PLT ≥ 50 × 10In terms of safety, several randomized controlled studies and real-clinical evidence have suggested that lusutrombopag was well tolerated, being the same as that seen in this study [Additionally, patients with liver cirrhosis are often associated with a potentially increased risk of vein thrombosis, and the use of TPO-RAs may further increase the risk of thrombosis [It is worth noting that, unlike in Japan, Europe or America, hepatitis B is the main type of CLD in China, and the number of patients suffering from hepatitis B is about three times that of hepatitis C [The administration regimen of lusutrombopag in this study was another noteworthy difference from L-PLUS 1 and 2 studies. To prevent the potential risk of thrombosis due to an excessive increase in platelets after the administration of lusutrombopag, the dose-stopping rule was implemented for avoiding platelet-overshooting in the L-PLUS 1 and L-PLUS 2 studies. As an inference result of the previous studies, it is possible that there is little difference in the probability of PLT higher than 200 × 10A few limitations emerge in this work. First, while patients with Child–Pugh liver disease of class C that can be hospitalized at least between days 5 and 10 was one of the inclusion criteria, no such patients actually participated in the randomization. A study describing the pharmacokinetic characteristics of lusutrombopag showed a lower median AUC (area under the plasma concentration–time curve) of lusutrombopag in patients with Child–Pugh liver disease of class C was lower vs. the AUC in patients with Child–Pugh class A or B liver disease [In conclusion, for the treatment of patients with CLD having thrombocytopenia, who plan to undergo invasive elective treatment, once-daily intake of lusutrombopag at 3 mg continuously for seven days can effectively raise PLT to meet the criteria of invasive procedures, thus avoiding pre-procedure platelet transfusion without additional safety problems. Crucially, lusutrombopag could be a safe, effective, and reliable method for such patients being treated with an elective invasive approach in China.