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- Title
Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial.
- Authors
Schiffmann, Raphael; Bichet, Daniel G.; Jovanovic, Ana; Hughes, Derralynn A.; Giugliani, Roberto; Feldt-Rasmussen, Ulla; Shankar, Suma P.; Barisoni, Laura; Colvin, Robert B.; Jennette, J. Charles; Holdbrook, Fred; Mulberg, Andrew; Castelli, Jeffrey P.; Skuban, Nina; Barth, Jay A.; Nicholls, Kathleen
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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).<bold>Results: </bold>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).<bold>Conclusions: </bold>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.<bold>Trial Registration: </bold>NCT00925301 ; June 19, 2009.
- Subjects
DISEASE progression; BIOLOGICAL tags; ANGIOKERATOMA corporis diffusum; GASTROINTESTINAL diseases; CLINICAL trials
- Publication
Orphanet Journal of Rare Diseases, 2018, Vol 13, Issue 1, pN.PAG
- ISSN
1750-1172
- Publication type
journal article
- DOI
10.1186/s13023-018-0813-7