Because Type 1 Gaucher disease is variable, a patient-centered, goal-oriented approach is critical for achieving optimal outcomes. Yet, the procedures for establishing an individualized disease management plan can be similar for all Gaucher disease patients. The International Collaborative Gaucher Group (ICGG) has published a series of recommended therapeutic goals for Gaucher disease.1 The findings are summarized below.
Goal: < 1.5 x normal
(normal = 2.5% body weight)
||Lessen or eliminate bone pain
Prevent bone crises
|Years 1 to 2
||Improve and normalize BMD
|Adult Females and children
||> 11.0 g/dL
|Male > 12 years
||> 12.0 g/dL
||Sufficient platelets to reduce bleeding
||Normalization of platelet counts
(>60,000 - < 120,000/mm3)
|Low-normal platelet counts
|Continued increases but no normalization
The first step in setting therapeutic goals is an initial comprehensive assessment of all potential disease manifestations: anemia, thrombocytopenia, hepatomegaly, splenomegaly, skeletal pathology, growth retardation in pediatric patients, pulmonary involvement, functional health and well-being, and a thorough physical examination. The information obtained should then be used to establish therapeutic goals for all disease compartments. The recommended primary assessments are:
|Overall clinical assessment
||Complete patient and family history, preferably including pedigree
Comprehensive physical examination (annual)
Quality of Life (annual); patient-reported using SF-36
Biochemical markers (chitotriosidase, ACE, or TRAP)
|Additional blood tests (based on age and clinical status)
||WBC, PT, and PTT
Iron, iron binding capacity, ferritin, vitamin B12
AST and/or ALT; alkaline phosphatase, calcium, phosphorous, albumin, total protein, total and direct bilirubin
||MRI (coronal; T1 and T2 weighted) of the entire femora
DXA lumbar spine and femoral neck
X-ray (AP view of the entire femora) and lateral view of the spine
||Volume and structure of spleen and liver by MRI or CT (or ultrasound)
Contiguous transaxial 10mm thick sections for sum of region of interest
||ECG, chest X-ray and Doppler echo for right ventricular systolic pressure
||Beta-glucosidase and mutation analysis
Other parameters that should be monitored:
- Physical examination results should improve
- Stabilize or decrease serial measurements of the biomarkers chitotriosidase, TRAP, or ACE
- Quality of Life (QoL)
- Improve or restore physical function for normal daily activities
- Improve scores on validated QoL instrument within 2 to 3 years or less
According to data from the Gaucher Registry, most patients are able to achieve these therapeutic goals with the proper dosing. The highest success rates have been seen in bone crises, liver volume, and hemoglobin.2
One-hundred and ninety-five Type 1 Gaucher disease patients enrolled in the Gaucher Registry were evaluated for achievement of published therapeutic goals. After 48 months of treatment with Cerezyme, the proportion of
patients who met all six therapeutic goals increased from 2.1% at first infusion to 41.5% at 4 years; ≥5 goals
from 12.8% to 76.9%; ≥4 goals from 37.4% to 92.8%; ≥3 goals from 70.8% to 99.0%; and ≥2 goals from
95.4% to 99.5%. All patients met at least one goal at first infusion and after 4 years of treatment. The proportion
of patients meeting specific therapeutic goals increased for all parameters between first infusion
and 4 years of therapy: platelet count (24.6%–79.5%), spleen volume (25.6%–78.5%), liver volume (45.6%–
90.8%), bone pain (62.6–70.3%), hemoglobin (68.2–91.8%), and bone crises (91.8–99.0%). On average,
patients who received higher doses of imiglucerase achieved a greater number of therapeutic goals.
It is recommended that patients who are unable to maintain their therapeutic goals on a lower dose should return to the therapeutic dosing that enabled them to achieve their goals. Routine or comprehensive monitoring is recommended.
Indication & Usage
Cerezyme® (imiglucerase for injection) is indicated for long-term enzyme replacement therapy for pediatric and adult patients with a confirmed diagnosis of Type 1 Gaucher disease that results in one or more of the following conditions:
- bone disease
- hepatomegaly or splenomegaly
Important Safety Information
Approximately 15% of patients have developed IgG antibodies to Cerezyme during the first year of therapy. Approximately 46% of patients with detectable IgG antibodies experienced symptoms of hypersensitivity, and these patients have a higher risk of hypersensitivity. It is suggested that patients be monitored periodically for IgG antibody formation during the first year of treatment.
Hypersensitivity has also been observed in patients without detectable IgG antibodies. Symptoms suggestive of hypersensitivity have been noted in approximately 6.6% of all patients, and anaphylactoid reactions in less than 1%. Treatment with Cerezyme should be approached with caution in patients who have exhibited hypersensitivity symptoms such as pruritus, flushing, urticarial, angioedema, chest discomfort, dyspnea, coughing, cyanosis, and hypotension. Pre-treatment with antihistamines and/or corticosteroids and a reduced rate of infusion may allow continued treatment in most patients.
In less than 1% of patients, pulmonary hypertension and pneumonia have been observed during treatment with Cerezyme. These are known complications of Gaucher disease regardless of treatment. Patients with respiratory symptoms in the absence of fever should be evaluated for the presence of pulmonary hypertension.
Approximately 13.8% of patients have experienced adverse events related to treatment with Cerezyme. Some of these are injection site reactions such as discomfort, pruritus, burning, swelling or sterile abscess at the site at the site of venipuncture. Additional adverse reactions that have been reported include nausea, abdominal pain, vomiting, diarrhea, rash, fatigue, headache, fever, dizziness, chills, backache, and tachycardia. Transient peripheral edema has also been reported for this therapeutic class of drug.
To report suspected adverse reactions, contact Genzyme at 800-745-4447, option 2 or FDA at 800-FDA-1088 or http://www.fda.gov/Safety/MedWatch
Please see Full Prescribing Information (PDF).
Pastores GM, Weinreb NJ, Aerts H, et al. Therapeutic goals in the treatment of Gaucher disease. Semin Hematol 2004:41(suppl 5);4-14.
Weinreb N, Taylor J, et al. A benchmark analysis of the achievement of therapeutic goals for type 1 Gaucher disease patients treated with imiglucerase. Am J Hematol. 2008;83(12):890–895.