Background: Gaucher disease type 1 (GD1) is a rare lysosomal storage disorder caused by glucocerebrosidase deficiency, leading to systemic complications such as hepatosplenomegaly, anemia, thrombocytopenia, and skeletal abnormalities. Enzyme replacement therapy (ERT) has long been the standard treatment; however, its biweekly intravenous infusions pose logistical challenges, especially in resource-limited regions like China. Eliglustat, an oral substrate reduction therapy (SRT), offers a more convenient and cost-effective alternative. While global trials have demonstrated Eliglustat's efficacy and safety, real-world evidence specific to Chinese GD1 patients remains scarce. This study provides the first multicenter, real-world evaluation of Eliglustat in this population, focusing on its effectiveness, safety, and potential as a first-line therapy in resource-limited settings.

Methods: This retrospective, multicenter study included adult GD1 patients from 15 hospitals across China who received Eliglustat for ≥6 months between November 2023 and July 2024. Eliglustat was administered at a fixed dose of 84 mg twice daily. Key clinical outcomes included plasma glucosylsphingosine (Lyso-GL1), hemoglobin (HGB), platelet count (PLT), liver volume, and spleen volume, assessed at baseline and follow-up. Safety was evaluated based on adverse events (AEs) graded per CTCAE v5.0.

Results: A total of 19 patients (male-to-female ratio: 9:10; median age: 36 years [range: 18–55]) were included, with a median follow-up duration of 7 months (range: 6–9). Lyso-GL1 levels decreased significantly from 468 ng/mL to 210 ng/mL (P < 0.0001). PLT increased significantly from 109 ×109/L to 132 ×109/L (P = 0.019), with 58.3% (7/12) of thrombocytopenic patients improving. Liver and spleen volumes decreased significantly (liver: 2128 mL to 1501 mL, P = 0.031; spleen: 961 mL to 786 mL, P = 0.032). HGB levels increased from 125 g/L to 134 g/L (P = 0.275), with 83.3% (5/6) of anemic patients showing improvement and 33.3% (2/6) achieving normalization. Subgroup analysis revealed greater Lyso-GL1 reductions in treatment-naïve patients compared to those transitioning from ERT (55.1% vs. 43.1%, P = 0.049). Grade I/II AEs were reported in 31.6% of patients, with no grade III or higher AEs, treatment discontinuations, or deaths.

Conclusion: Eliglustat showed significant real-world effectiveness and a favorable safety profile in Chinese GD1 patients, suggesting its potential as a first-line treatment in resource-limited settings where ERT access is challenging. While limited by small sample size and short follow-up, these findings align with global data and provide critical insights into GD1 management in China. Future long-term, prospective studies are warranted to validate these results and further explore Eliglustat's role in addressing unmet needs in this population.

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2025
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