BACKGROUND: In 2009, a worldwide supply constraint of imiglucerase led to treatment modifications or interruptions for patients with Gaucher disease (GD) type 1. In France, joint treatment recommendations were issued to protect the most vulnerable patients. This observational study evaluated the impact of imiglucerase treatment modifications on the clinical and biological course of GD.<br /><br />METHODS: Retrospective data on patients' characteristics, treatment, clinical and biological parameters from 01 June 2009 to 31 October 2010 were collected during a single visit.<br /><br />RESULTS: Ninety-nine GD1 patients, aged 7-84 years, were included (median age 47 years); 10 were children. Patients experienced a median of 4 different treatment modifications. Median change from pre-supply constraint dose (92 U/kg/4-weeks) was -69, -51, -29 and -60 U/kg/4-weeks at 3, 6, 9 and 12 months after first modification, respectively, with imiglucerase discontinuation reported for 70%, 47%, 29% and 55% of patients at these timepoints. Replacement with another ERT was reported for 35 patients. Results show a statistically significant decrease in hemoglobin (-0.8 g/L/month) and platelets (-5905.10(3)/mm(3)/month) and an increase in chitotriosidase (+537 nmol/mL/h/month) and angiotensin-converting enzyme (+4 IU/L/month) in the subgroup of 61 patients who discontinued treatment for at least 3 months; this magnitude of change was not seen in the subgroup (32 patients) treated with reduced imiglucerase for at least 3 consecutive months. GD-related events were spontaneously reported by the study investigators for 39% of the whole study population, including asthenia/fatigue (8%), bone infarction and bone pain (4% each), and hepatomegaly (3%). A Kaplan-Meier estimate of the probability for a patient to present a bone, hematological or visceral event during the constraint was 37% for patients who discontinued the treatment and 10% for patients treated with a reduced imiglucerase dose.<br /><br />CONCLUSION: The release of recommendations and individuals' close follow-up allowed satisfactory management of patients during the imiglucerase supply constraint in France. This study suggests that during this period, lowering the dose of imiglucerase had less impact on the outcomes of patients than interrupting treatment. However, general effects (such as fatigue, bone pain) reported in some patients, emphasize the importance of maintaining appropriate individualized dosing.
Stirnemann, J., Rose, C., Serratrice, C., Dalbies, F., Lidove, O., Masseau, A., … Belmatoug, N. (2015). Impact of imiglucerase supply constraint on the therapeutic management and course of disease in French patients with Gaucher disease type 1. Orphanet Journal of Rare Diseases, 10(1). https://doi.org/10.1186/s13023-015-0275-0