Review of the safety and efficacy of imiglucerase treatment of Gaucher disease

Abstract

Abstract:Most patients who suffer from symptomatic Gaucher disease will benefit from enzyme replacement therapy (ERT) with imiglucerase. The safety profile is excellent, only a small percentage of those exposed developing antibodies; similarly, very few patients require pre-medication for allergic reactions. Within 3 to 5 years of imiglucerase therapy, best documented at doses of 30 to 60 units/kg/infusion, hepatosplenomegaly can be expected to be reduced so that the liver volume will be maintained at 1 to 1.5 times normal (30% to 40% reduction from advent of ERT) and spleen volume to 2 to 8 times normal (50% to 60% reduction from advent of ERT). For anemic and thrombocytopenic patients, with 2 to 5 years of imiglucerase, hemoglobin levels are expected to be 11 g/dL for women and children and 12 g/dL for men; and platelet counts in patients with an intact spleen, depending on the baseline value, should approximately be doubled. Bone crises and bone pain but not irreversible skeletal damage will improve in most patients. Nonetheless, some features and some symptomatic patients apparently do not respond equally well and/or perhaps inadequately. The benefit for patients with the neuronopathic forms is primarily in improved visceral and hematological signs and symptoms. There are still several unresolved issues, the high per-unit cost being an important one, which have spurred the development of biosimilar enzymes as well as chaperone therapies currently in clinical trials.

A Feasibility Open-Labeled Clinical Trial Using a Second-Generation Artificial-Intelligence-Based Therapeutic Regimen in Patients with Gaucher Disease Treated with Enzyme Replacement Therapy

“…More extended observation periods are expected to achieve an effect. In addition, it has been recently suggested that GD-specific patient-reported outcome measures (PROM) may be more relevant to showing small, meaningful changes, and these should be used in the subsequent study [ 7 , 8 ].…”

“…Since 1991, intravenous enzyme replacement therapy (ERT) has become the standard of care, improving almost all GD-related features, improving anemia and thrombocytopenia, reducing organomegaly (liver and spleen), and alleviating skeletal findings [ 5 , 6 , 7 ]. Therapy goals include hematological, visceral, and bone manifestations and improvement in quality of life, fatigue, and social participation [ 8 ].…”

Quantitative analysis of recombinant glucocerebrosidase brain delivery via lipid nanoparticles

“…ERT has emerged as the standard of care for type I GD [8,9]. Over two decades since the introduction of this therapy [10], it has become clear that many of the symptoms and signs of visceral GD respond adequately to ERT [11]. Despite its great success, ERT also has disadvantages, including costly manufacture, inconvenience of the intravenous infusions and the inability of the intravenously administered enzyme to cross the blood-brain barrier (BBB).…”