Never-Treated, Non Splenectomised Patients With Gaucher Disease (The French GANT Study): The Prospective Follow-Up

Treatment options for Type 1 Gaucher Disease (GD1) include enzyme replacement therapy and oral substrate reduction therapy. The criteria for treatment initiation vary across regions. Recent retrospective studies have highlighted the natural progression of never-treated GD1, suggesting that some patients remain asymptomatic or stable for extended periods. However, there is no data on long-term prospective follow-up. We conducted a prospective study following a cross-sectional analysis of 36 never-treated, non-splenectomised GD1 patients from the French Gaucher Disease Registry (FGDR). The objective was to describe the natural disease progression, tracking clinical, radiological, and biological characteristics over time. Thirty-six non-splenectomised and never-treated patients (19 women and 17 men) diagnosed with Gaucher Disease were prospectively followed for an additional median duration of 6.5 (5-8.3) years. Of the cohort, 17 remained untreated, 10 initiated treatment, and 7 were lost to follow-up. Although never-treated patients tended to be older at the time of first symptoms, diagnosis, and last follow-up compared to those who received treatment, the difference was not significant in this small cohort. At last follow-up, never-treated patients had no worsening of most of their symptoms. No significant changes were observed in platelets, chitotriosidase, and lyso-Gb1. In this prospective cohort, we highlight that patients with mild GD can remain untreated with no disease progression, offering insights into cost-effective management strategies. Identifying such patients is still challenging.