Nonprecipitous changes upon withdrawal from imiglucerase for Gaucher disease because of a shortage in supply.
Because of an unpredicted and unavoidable shortage in global supplies of imiglucerase for Gaucher disease, we collected clinical and laboratory data from patients who were evaluated ≤ 6months before drug withdrawal and then retested before/during reinstatement of therapy. Hemoglobin, platelet counts, and liver and spleen index volumes by ultrasound as well as chitotriosidase were evaluated as percent change over time and relative to dose-years of exposure to enzyme therapy. Deterioration was seen in all four clinical parameters and in chitotriosidase activity in most patients and even among patients who stopped for only 3 months. No patient consistently showed nondeterioration in all five parameters. Platelet counts were most sensitive to therapy withdrawal. There was no overt correlation between percent change in these parameters and dose-years of therapy. Although we no longer think that drug vacations should be considered as a form of maintenance for patients requiring enzyme therapy for Gaucher disease, but if necessary-for compelling personal reasons-one may be reassured that a short-term drug interruption is not likely to lead to irreversible complications or return to baseline values of critical clinical parameters.
Zimran
Ari
A
Gaucher Clinic and Genetics Unit, Shaare Zedek Medical Center, Jerusalem, Israel.
Altarescu
Gheona
G
Elstein
Deborah
D
D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D005260:Female; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D005962:Glucosylceramidase / Q000600:supply & distribution* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D012720:Severity of Illness Index; D016896:Treatment Outcome
D005962:Glucosylceramidase; C090568:imiglucerase