The following recommended goals are based upon composite information obtained from the Gaucher Registry. Patient responses may vary and physicians should use their own medical judgment in applying these recommendations in the care of their patients.

Bone Disease
Anemia
Thrombocytopenia
Hepatomegaly
Splenomegaly

Hepatomegaly

Hepatomegaly is defined as a liver mass more than 1.25 times the normal 2.5% of total body weight in kilograms. Liver enlargement is assessed by quantitative imaging, preferably using MRI or CT.

Reduction in hepatomegaly is influenced by baseline liver volume and this is supported by data from the Gaucher Registry. Patients with moderate hepatomegaly (liver volume >1.25 and ≤2.5 times normal) were more likely to achieve liver volume normalization: 50% (splenectomized) to 58% (intact spleen) of patients with moderate hepatomegaly pretreatment achieved a liver volume <1.25 times normal after 24 months of enzyme replacement therapy (ERT) compared with 6% to 9% of patients with severe hepatomegaly (>2.5 times normal volume) pretreatment. The reduction in hepatomegaly was greatest during the first 2 years of ERT, and liver volumes in those with severely enlarged livers continued to decrease at a slower rate during years 3 to 5.

Therefore, therapeutic goals for patients with hepatomegaly are to reduce and then maintain the liver volume to 1.0 to 1.5 times normal. Liver volume should decrease by 20% to 30% within years 1 to 2 and by 30% to 40% by years 3 to 5.

Volume normalization is generally not possible when hepatomegaly is severe, presumably because of the presence of fibrosis. Data on the impact of ERT for prevention of hepatic infarction, fibrotic scarring, progression to cirrhosis, portal hypertension, and hepatopulmonary syndrome are currently limited.

If therapeutic goals for hepatomegaly are not met, screening for intercurrent conditions (eg, viral hepatitis, chronic hepatitis, autoimmune liver disease, iron overload) should be performed, especially in patients with highly abnormal liver function test results and/or advanced liver disease. Some patients with established cirrhosis and hepatic failure will require allogeneic hepatic transplantation.

For more information about hepatomegaly, please contact Genzyme Medical Affairs at 1-800-745-4447.

Important Safety Information

Adverse reactions related to Cerezyme® (imiglucerase for injection) administration have been reported in less than 15% of patients. Each of the following events occurred in less than 2% of the total patient population. Reported adverse events include nausea, vomiting, abdominal pain, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Adverse events associated with the route of administration include discomfort, pruritus, burning, swelling or sterile abscess at the site of venipuncture. Symptoms suggestive of hypersensitivity include anaphylactoid reaction, pruritus, flushing, urticaria, angioedema, chest discomfort, dyspnea, coughing, cyanosis and hypotension. Approximately 15% of patients have developed IgG antibodies; periodic monitoring is suggested. Side effects should be reported promptly to Genzyme Medical Information at 800-745-4447, option 2. To learn more, please see full product information (PDF), or contact Genzyme at 1-800-745-4447.

Weinreb NJ, Charrow J, Andersson HC, et al. Effectiveness of enzyme replacement therapy in 1,028 patients with type 1 Gaucher disease after 2-5 years of treatment: a report from the Gaucher Registry. Am J Med. 2002; 113:112-119 .

Rosenthal DI, Doppelt SH, Mankin HJ, et al. Enzyme replacement therapy for Gaucher disease: skeletal responses to macrophage-targeted glucocerebrosidase. Pediatrics. 1995;96:629-637.

Charrow J, Andersson HC, Kaplan P, et al. The Gaucher registry: demographics and disease characteristics of 1698 patients with Gaucher disease. Arch Intern Med. 2000; 160:2835-2843.

Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol. 2004;41(4 suppl 5):4-14.