Schiffmann, RaphaelBichet, Daniel G.Jovanovic, AnaHughes, Derralynn A.Giugliani, RobertoFeldt-Rasmussen, UllaShankar, Suma P.Barisoni, LauraColvin, RobertJennette, J. CharlesHoldbrook, FredMulberg, AndrewCastelli, Jeffrey P.Skuban, NinaBarth, Jay A.Nicholls, Kathleen2018-06-272018Schiffmann, R., D. G. Bichet, A. Jovanovic, D. A. Hughes, R. Giugliani, U. Feldt-Rasmussen, S. P. Shankar, et al. 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): 68. doi:10.1186/s13023-018-0813-7. http://dx.doi.org/10.1186/s13023-018-0813-7.http://nrs.harvard.edu/urn-3:HUL.InstRepos:37160128Background: 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.en-USAmenable mutationDiarrheaFabry diseaseGastrointestinalGlobotriaosylceramideGSRSLyso-GbMigalastatPharmacological chaperoneJournal Article2018-06-2710.1186/s13023-018-0813-7