Miglustat: new drug. In type 1 Gaucher's disease : a slight benefit after imiglucerase therapy.

(1) For patients with type 1 Gaucher's disease the standard treatment is imiglucerase enzyme replacement therapy, provided in fortnightly intravenous infusions. (2) Miglustat inhibits the synthesis of glucosyl-ceramide, the cerebroside that accumulates in Gaucher's disease. Miglustat is now licensed for oral therapy in patients with mild to moderate type 1 Gaucher's disease and who cannot take imiglucerase, regardless of the reason. (3) The evaluation data we managed to gather (see literature search) includes data from three trials involving a total of 82 patients. One of these trials compared miglustat with ongoing imiglucerase therapy. Miglustat slightly reduced the size of the liver and spleen, and slightly increased the haemoglobin level and platelet count after 18 months. The impact of these effects is unknown, especially on bone disorders. In patients with previous response to imiglucerase, miglustat has not been found to maintain clinical effects in the longer term. (4) Miglustat has many adverse effects, some of which occur very frequently, such as diarrhea (86%), weight loss (64%), peripheral neuropathies (19%), tremor (29%), and cognitive disorders. Animal studies suggest a risk of reproductive toxicity. (5) In practice, miglustat therapy offers minimal benefits for the few patients who cannot use imiglucerase. The potential advantages of miglustat therapy relative to purely symptomatic treatment must be carefully weighed in individual patients.