Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial
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BACKGROUND: Fabry disease is frequently characterized by gastrointestinal symptoms, including diarrhea. Migalastat is an orally-administered small molecule approved to treat the symptoms of Fabry disease in patients with amenable mutations.
METHODS: We evaluated minimal clinically important differences (MCID) in diarrhea based on the corresponding domain of the patient-reported Gastrointestinal Symptom Rating Scale (GSRS) in patients with Fabry disease and amenable mutations (N = 50) treated with migalastat 150 mg every other day or placebo during the phase 3 FACETS trial (NCT00925301).
RESULTS: After 6 months, significantly more patients receiving migalastat versus placebo experienced improvement in diarrhea based on a MCID of 0.33 (43% vs 11%; p = .02), including the subset with baseline diarrhea (71% vs 20%; p = .02). A decline in kidney peritubular capillary globotriaosylceramide inclusions correlated with diarrhea improvement; patients with a reduction > 0.1 were 5.6 times more likely to have an improvement in diarrhea than those without (p = .031).
CONCLUSIONS: Migalastat was associated with a clinically meaningful improvement in diarrhea in patients with Fabry disease and amenable mutations. Reductions in kidney globotriaosylceramide may be a useful surrogate endpoint to predict clinical benefit with migalastat in patients with Fabry disease.
TRIAL REGISTRATION: NCT00925301 ; June 19, 2009.
Original language | English |
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Article number | 68 |
Journal | Orphanet Journal of Rare Diseases |
Volume | 13 |
Number of pages | 7 |
ISSN | 1750-1172 |
DOIs | |
Publication status | Published - 2018 |
- 1-Deoxynojirimycin/analogs & derivatives, Adolescent, Adult, Aged, Biomarkers/metabolism, Diarrhea/drug therapy, Fabry Disease/drug therapy, Female, Humans, Kidney/metabolism, Male, Middle Aged, Mutation/genetics, Trihexosylceramides, Young Adult
Research areas
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