Dose-response relationships for enzyme replacement therapy with imiglucerase/alglucerase in patients with Gaucher disease type 1

Purpose: To determine whether enzyme therapy with imiglucerase/ alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients. Methods: Analyses included all patients with Gaucher disease type 1 on enzyme therapy and with intact spleens in the large observational database of the International Collaborative Gaucher Group Gaucher Registry. Propensity scoring was used to match patients between enzyme therapy dose groups categorized as Group A (5 U to <29 U/kg/2 weeks). Group B (29 U to <48 U/kg/2 weeks), Group C (48 U to <75 U/kg/2 weeks). Hemoglobin concentration, platelet count, and hepatic and splenic volumes were assessed after initiation of en-zyme therapy using nonlinear mixed effects models. The maximal effect (E_max) and half-time to E_mix (T₅₀) of enzyme therapy for each parameter were compared across dosing groups. Results: Propensity score matching resulted in three comparable groups of 122 patients each (enzyme therapy in Groups A, B, and C). Dose-response relationships were found with regard to E_max and T₅₀ over 96 months for each disease parameter. Conclusions: Enzyme therapy with imiglucerase/alglucerase displays a dose-dependent improvement in hematological and visceral parameters in Gaucher disease type 1 patients. Group C displayed greater treatment effects than Groups A or B. Propensity score matching and nonlinear mixed effects model analyses provide a prototype for assessment of treatment outcomes based on observational data from international rare disease registries.