Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial
AuthorSchiffmann, R; Bichet, DG; Jovanovic, A; Hughes, DA; Giugliani, R; Feldt-Rasmussen, U; Shankar, SP; Barisoni, L; Colvin, RB; Jennette, JC; ...
Source TitleOrphanet Journal of Rare Diseases
University of Melbourne Author/sNicholls, Kathleen
AffiliationMedicine and Radiology
Document TypeJournal Article
CitationsSchiffmann, R., Bichet, D. G., Jovanovic, A., Hughes, D. A., Giugliani, R., Feldt-Rasmussen, U., Shankar, S. P., Barisoni, L., Colvin, R. B., Jennette, J. C., Holdbrook, F., Mulberg, A., Castelli, J. P., Skuban, N., Barth, J. A. & Nicholls, K. (2018). Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial. ORPHANET JOURNAL OF RARE DISEASES, 13 (1), https://doi.org/10.1186/s13023-018-0813-7.
Access StatusOpen Access
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.
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