Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial.

Journal Article (Clinical Trial, Phase III;Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Schiffmann, R; Bichet, DG; Jovanovic, A; Hughes, DA; Giugliani, R; Feldt-Rasmussen, U; Shankar, SP; Barisoni, L; Colvin, RB; Jennette, JC; Holdbrook, F; Mulberg, A; Castelli, JP; Skuban, N; Barth, JA; Nicholls, K

Published Date

  • April 27, 2018

Published In

Volume / Issue

  • 13 / 1

Start / End Page

  • 68 -

PubMed ID

  • 29703262

Pubmed Central ID

  • PMC5923014

Electronic International Standard Serial Number (EISSN)

  • 1750-1172

Digital Object Identifier (DOI)

  • 10.1186/s13023-018-0813-7


  • eng

Conference Location

  • England