Comparative efficacy of dose regimens in enzyme replacement therapy of type I Gaucher disease

Gaucher disease is caused by a deficiency of P-glucocerebrosidase activity. The optimum dose and frequency of enzyme replacement therapy for Gaucher p atients have not been determined. We set to compare the therapeutic effects of initiating treatment with macrophage-targeted glucocerebrosidase at a h igh dose followed by progressive dose reductions with that produced by init ial treatment at a low dose in patients with type I Gaucher disease. The st udy included two parts: (i) Twelve patients received every 2 weeks enzyme r eplacement 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) Thi rty-two patients received enzyme replacement therapy at 10 IU/kg every 2 we eks 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 pho sphatase, and organ volume improved or remained unchanged at the end of eac h dose reduction. Platelet count decreased significantly when the dose of e nzyme was reduced from 30 to 15 IU/kg body wt. Initiation of therapy at a l ow 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 nonskele tal manifestations of Gaucher disease can be achieved either by initiating enzyme replacement therapy with a high dose followed by a stepwise dose red uction or by starting treatment at the minimal dose. High dose provides a f aster clinical response and should be considered for patients with more agg ressive disease. The therapeutic threshold for macrophage-targeted glucocer ebrosidase appears to be 10-15 IU/kg body wt every 2 weeks. (C) 2000 Academ ic Press.