Increased intervals in enzyme replacement therapy for stable type 1 Gaucher disease: A non-inferiority sequential...

Area of Science:

• Rare diseases
• Genetics
• Metabolic disorders

Background:

• Gaucher disease (GD) is a rare genetic disorder requiring enzyme replacement therapy (ERT).
• Standard ERT is administered biweekly (Q2W).
• Extended interval ERT (Q3-4W) may offer benefits for stable patients.

Purpose of the Study:

• To compare the efficacy and safety of extended interval (Q3-4W) ERT versus standard biweekly (Q2W) ERT.
• To evaluate the non-inferiority of Q3-4W ERT in clinically stable type 1 Gaucher disease (GD) patients.

Main Methods:

• A target trial emulation with a sequential design using French GD Registry data.
• Matching of 63 switchers to Q3-4W ERT with 215 Q2W ERT patients based on clinical and demographic factors.
• Primary outcome: composite of GD-related clinical events; non-inferiority margin of 10%.

Main Results:

• No significant difference in clinical event risk between Q3-4W and Q2W ERT groups (HR: 0.98 [95% CI: 0.54-1.51]).
• Absolute risk difference remained below the 10% non-inferiority threshold throughout follow-up.
• Biomarkers remained stable or slightly decreased in the Q3-4W group, with significant cost savings (€450,000 per patient over 6 years).

Conclusions:

• Extended interval (Q3-4W) ERT is non-inferior to standard biweekly (Q2W) ERT in stable GD1 patients.
• Personalized ERT spacing strategies can enhance patient quality of life.
• Q3-4W ERT reduces healthcare costs associated with Gaucher disease management.