Comparative Efficacy of Dose Regimens in Enzyme Replacement Therapy of Type I Gaucher Disease

Abstract ABSTRACT Gaucher disease is caused by a deficiency of β-glucocerebrosidase activity. The optimum dose and frequency of enzyme replacement therapy for Gaucher patients have not been determined. We set to compare the therapeutic effects of initiating treatment with macrophage-targeted glucocerebrosidase at a high dose followed by progressive dose reductions with that produced by initial treatment at a low dose in patients with type I Gaucher disease. The study included two parts: (i) Twelve patients received every 2 weeks enzyme replacement therapy at 60 IU/kg body wt for 24 months followed by sequential dose reduction every 6 months to 30 and then to 15 IU/kg body wt. (ii) Thirty-two patients received enzyme replacement therapy at 10 IU/kg every 2 weeks for 12 months. Hematologic parameters and liver and spleen volume were monitored in all patients. All patients had intact spleens. In patients who were started on high-dose enzyme replacement therapy, hemoglobin, acid phosphatase, and organ volume improved or remained unchanged at the end of each dose reduction. Platelet count decreased significantly when the dose of enzyme was reduced from 30 to 15 IU/kg body wt. Initiation of therapy at a low dose led to a significant improvement in all measured parameters at the end of 1 year. We conclude that the minimal effective dose for the nonskeletal manifestations of Gaucher disease can be achieved either by initiating enzyme replacement therapy with a high dose followed by a stepwise dose reduction or by starting treatment at the minimal dose. High dose provides a faster clinical response and should be considered for patients with more aggressive disease. The therapeutic threshold for macrophage-targeted glucocerebrosidase appears to be 10–15 IU/kg body wt every 2 weeks.