Substrate Reduction Therapy With Miglustat In Type 1 Gaucher Disease In Spain. Nine Years Outcomes Update On ZAGAL Study

Substrate reduction therapy (SRT) has showed as an useful therapy in type 1 GD patients with mild or moderate disease. The main limitation to use miglustat has been the gastrointestinal adverse events. Since 2004 we have conducted the ZAGAL (Zavesca en Gaucher Leve) study for monitoring the real-life use of miglustat in Spanish adult patients with mild-to moderate disease. The study included GD1 patient’s naïve to therapy as well as patients who have previously been treated with ERT. For follow-up, the therapeutic goals for GD therapy by Pastores GM et al were applied. To date a total of 351 GD1 patients have been diagnosed in Spain (FEETEG unpublished. 2013); from 2004 until 2013, 53 of them have been exposed of miglustat (15.1%). In 16 patients (30.2%) miglustat was the first line of therapy and the remaining 38 switched from ERT. Currently 37 patients (mean age 43.6 y, range 22-83) 50.9% females, are on miglustat therapy (20 at least for 5 years and 13 during more than 8 years). Related to efficacy, the therapy permit to achieve a stable hemoglobin concentration level and spleen reduced volume, but we recorded a decrease of absolute platelet count in 15 patients (28.3%) (mean: 35x109/L, range: 10-86x109/L). Related to biomarkers changes an increase in CT activity was observed in 56.6% of patients (mean: 2,448 nmol/mL.h, range 135-13,687) and 43.4 % for CCL18/PARC (mean: 250 ng/mL, range: 19-1016). Seventeen patients (32.1%) had transitory gastrointestinal disturbances. Sixteen patients (30.2%) discontinued therapy: one of them for pregnancy, two by bone crisis, two by weight loss, one for bad compliance and ten by gastrointestinal discomfort or intolerance (18.8%). 60% of patients has a fine tremor in first months on therapy. 4 died by non-related causes (2 cancer, 1 hearth attack, 1 liver failure), Conclusion The long term follow-up of GD patients treated with Miglustat shows that more than 69% had achieved and maintains the therapeutic goals. A high individual variability had been observed related to miglustat gastrointestinal intolerance apparently no related with GBA genotype, gender and age, but possibly associated with disacaridases inhibition and food habits. Disclosures: No relevant conflicts of interest to declare.