2020年 · 第100卷第42期

Eliglustat is a first-line oral substrate-reducing therapy for adult patients with type I Gaucher's disease and has been approved in the United States, Europe and Japan. Patients with Gaucher's disease require lifelong treatment, so the safety and effectiveness of long-term treatment with drugs are of paramount importance. This study explores the results of a phase 2 trial and an extension trial (NCT00358150) in adult patients with type I Gaucher disease and is the longest experience with eliglustat therapy to date. Patients with splenomegaly and Gaucher's disease type I with thrombocytopenia and/or anemia from June 2006 to October 2007 were collected, none of whom had received relevant treatment prior to enrollment in the clinical trial. Treatment with 50 or 100 mg eliglustat tartrate twice daily for 8 years. Nineteen of 26 patients with Gaucher's disease completed the trial. After 8 years of eliglustat treatment, the mean spleen and liver volumes of patients decreased by 69% and 34%, respectively. Mean hemoglobin concentrations and platelet counts increased by 2.2 g/dl and 113%, respectively. Severe splenomegaly (n=6), moderate to severe anemia (n =6) or severe thrombocytopenia (n=8) The final mean values of patients were close to those of patients with milder disease, and both reached the threshold of long-term treatment goals. Patients had a 91% decrease in chitosan, an 87% decrease in CCL18, a 92% decrease in glucosphingosine, and an 80% decrease in plasma gluconoylceramide compared with the median biomarker compared to pre-treatment baseline values. lumbar spinetThe mean score increased by 0.96, returning from osteopenia to the normal range. These patients had mostly lower-than-normal quality of life scores at baseline, and the mean quality of life scores after treatment were within the range of healthy adults. Eliglustat was well tolerated, 98% of the adverse events were mild or moderate, and 94% were considered unrelated to treatment. The study concluded that clinically meaningful improvements in blood, visceral, bone and biomarkers were achieved in patients with type I Gaucher disease after 1 year of eliglustat treatment. During 8 years of eliglustat treatment, the clinical indications of improvement in patients with type I Gaucher's disease continued to improve or remained, with the greatest improvement in severe patients.