Switching From Imiglucerase to Miglustat for the Treatment of French Patients With Gaucher Disease Type 1: A Case Series

Christine Serratrice; Laure Swiader; Jacques Serratrice


J Med Case Reports. 2015;9(146) 

In This Article

Abstract and Introduction


Introduction: Gaucher disease is caused by a deficiency of the enzyme β-glucocerebrosidase. Treatment with enzyme replacement therapy has been available for the past two decades but, although effective, enzyme replacement therapy can be delivered only by intravenous infusion every other week. The oral substrate reduction therapy miglustat (Zavesca®) has been available in Europe since 2002 for the treatment of patients with mild or moderate Gaucher disease type 1 for whom enzyme replacement therapy is unsuitable or not a therapeutic option. There are few published real-world data on the use of miglustat as a maintenance therapy in Gaucher disease type 1 patients switched from previous enzyme replacement therapy. We report a case series of three patients who were switched from long-term enzyme replacement therapy to miglustat for various reasons.

Case presentation: All three patients were Caucasian and had confirmed Gaucher disease type 1. An 80-year-old man requested a switch to oral miglustat therapy in preference to ongoing intravenous enzyme replacement therapy, a 57-year-old woman was commenced on miglustat due to a shortage of imiglucerase, and a 56-year-old woman was switched from previous enzyme replacement therapy due to allergic reactions to intravenous infusions. Hematological disease parameters were stable in each patient on previous enzyme replacement therapy. Two patients continue to be treated with miglustat, having shown good tolerability and stable core disease parameters for approximately 4 years. One patient, who was also stable during 7 years of therapy, eventually discontinued miglustat as a precaution because he developed peripheral neuropathy of as yet unknown origin.

Conclusions: Overall, our experience indicates that miglustat can be used as maintenance therapy for Gaucher disease type 1 after initial enzyme replacement therapy, but the selection of patients to whom this approach should be applied should be made after careful consideration of all disease parameters.


Gaucher disease (GD) is an inherited lysosomal disorder caused by impaired activity of the enzyme, β-glucocerebrosidase, and accumulation of glucosylceramide in pathologic macrophages in various tissues including the liver, spleen and bone marrow.[1] GD type 1 (GD1) is the most common clinical variant, and is characterized by anemia, thrombocytopenia, hepatosplenomegaly and various skeletal manifestations.[1,2]

Enzyme replacement therapy (ERT) with imiglucerase (Cerezyme®; Genzyme Corp.) represented the only therapy for GD1 for more than a decade. ERT is well established as being effective in reducing the hematological, visceral and bone symptoms of GD1.[3,4] However, it comes with a substantial therapeutic burden due to the need for regular intravenous infusions.

Oral substrate reduction therapy (SRT) with miglustat (Zavesca®; Actelion Pharmaceuticals) was approved in the European Union, USA and various other countries for the treatment of adults with mild or moderate GD1 for whom ERT is unsuitable/not a therapeutic option based on data from several clinical trials.[5–7] Miglustat has become an alternative treatment strategy to ERT, with potential therapeutic effects on bone manifestations.[8]

The switching of patients with GD1 from ERT to miglustat treatment was subject to intense focus during the global shortage of imiglucerase from 2009 to 2010,[9] but there were few published data on maintenance therapy with miglustat in patients with GD1 switched from previous ERT to draw upon at that time.[10] Since then, findings from a clinical non-inferiority trial assessing the effectiveness, safety and tolerability of miglustat as maintenance therapy in 42 patients with GD1 stabilized on previous ERT indicated satisfactory maintenance of core disease parameters.[11] Data from a cohort study with 115 patients treated with miglustat, 70% of whom previously received ERT, indicated a general stability of hematological parameters in patients who previously received ERT.[12]

Overall, available reported data from patients switched from previous ERT suggest that responses to SRT can vary. However, there are few reports detailing issues related to clinical decision making in terms of (1) the reasons for switching to oral SRT, (2) patient factors that affect responses to SRT, and (3) discontinuation of SRT in cases of adverse events (whether drug related or not). The following report describes clinical experience with three different cases, where patients switched from imiglucerase to miglustat for a variety of reasons.