Enzyme therapy in Gaucher disease type 1: dosage efficacy and adverse effects in 33 patients treated for 6 to 24 months

Abstract

Gaucher disease is the most frequent lysosomal storage disease and the most prevalent genetic disease among the Ashkenazi Jews (q approximately 0.047). The disease results from inherited defects of acid beta-glucosidase and the accumulation of the substrate, glucosylceramide, in cells of monocyte/macrophage origin. The therapeutic response to macrophage-targeted (alpha-mannosyl-terminated) alglucerase (Ceredase, at 60 to 15 IU/kg every 2 weeks) was analyzed in 33 patients (age range, 2 to 63 years; 15 splenectomized) with extensive Gaucher disease over periods of 6 to 24 months. The efficacy of several different doses and dosage reductions was evaluated. In patients with anemia (n = 30) and/or thrombocytopenia (n = 19), hemoglobin levels and platelet counts increased by 0% to 178% and 15% to 155%, respectively, within 3 to 12 months. In patients with splenomegaly (n = 17) and/or hepatomegaly (n = 28), liver and spleen volumes decreased in 6 months from 7% to 64% and 8% to 84% by 12 months, respectively. Hematologic and visceral improvements were noted at any doses between 60 and 15 IU/kg every 2 weeks. Furthermore, these positive initial therapeutic responses were persistent throughout therapy, with doses reduced by 50%. Pulmonary Gaucher disease did not improve clinically in 3 patients. Unrelated cirrhotic (n = 2), cholestatic (n = 1), or renal disease (n = 1) did not influence the rate of patient improvement. Two of five patients who developed serum antibodies against alglucerase during the first 6 to 12 months of therapy had mild antibody reactions. This study shows similar regression of clinical Gaucher disease manifestations with enzyme therapy, using doses between 30 and 60 IU/kg every 2 weeks. Therapeutic efficacy was not diminished after 50% to 75% dose reductions or in the presence of anti-enzyme antibodies.

Long‐term clinical outcomes in type 1 Gaucher disease following 10 years of imiglucerase treatment

“…1993; Weinreb et al 2002) describe the effects of alglucerase/ imiglucerase treatment after 6 months to 5 years. Pastores et al (1993) and Weinreb et al (2002) reported improvements in all hematological and visceral organ parameters within the first 6 months to 2 years of therapy. Specifically, Weinreb et al (2002) reported that patients with anemia achieved normal hemoglobin levels within 2 years of starting imiglucerase, and hemoglobin levels were sustained or increased during the initial 5 years of therapy.…”

Enzyme replacement therapy for mild patients with Gaucher disease

“…Enzyme replacement therapy (ERT) for patients with Gaucher disease was first introduced in 1991 [28] as a placenta-derived product [29] and then in recombinant form [30,31]; each has proven to be effective in management of the key disease parameters including reduction in organomegaly, improvement in hematological and biochemical parameters, decrease in bone-related pain, and compensatory growth in children. However, ERT probably cannot reverse nor halt the course of preexisting destructive skeletal complications [32].…”

Pulmonary involvement in Type 1 Gaucher disease: functional and exercise findings in patients with and without clinical interstitial lung disease

“…ERT with alglucerase (Ceredase) or imiglucerase (Cerezyme) has been shown to result in hematopoietic reconstitution and reduction of hepatosplenomegaly (27). However, its effect on lung involvement remains to be established.…”