Résumé
Objective To compare the efficacy and safety of extended interval (Q3–4W) enzyme replacement therapy (ERT) versus standard biweekly (Q2W) ERT in clinically stable type 1 Gaucher disease (GD) patients. Methods We emulated a target trial with a sequential trial design, using data from the French Gaucher Disease Registry. Eligible patients were treated for ≥2 years biweekly without clinical events. Every 3 months, switchers to Q3–4W were matched to Q2W patients by age, sex, referral center follow‐up, disease history (bone events, anemia, thrombocytopenia, splenectomy, and hepatosplenomegaly), and dose of ERT. The primary outcome was a composite of GD‐related events (bone events, anemia, and thrombocytopenia). A 10% non‐inferiority margin was prespecified. Secondary outcomes were biomarker changes and economic analyses. Results Among 280 eligible GD patients, 63 switched to Q3–4W and were matched to a total of 215 Q2W patients, followed for an average of 6.3 years. No significant difference in the risk of clinical events was observed between groups (hazard ratio: 0.98 [95% confidence intervals (CI): 0.54–1.51]). During follow‐up, absolute risk difference remained below the 10% non‐inferiority threshold at all timepoints. Biomarkers remained stable or slightly decreased in the Q3–4W group. The dosing interval extension led to an average reduction of 55 infusions per patient, corresponding to approximately €450,000 saved per patient over 6 years. Conclusion In stable GD1 patients, extending ERT administration to every 3–4 weeks was non‐inferior to the standard biweekly regimen, supporting personalized spacing strategies that may improve quality of life and reduce healthcare costs.