TY  - JOUR
AU  - Schiffmann, R
AU  - Bichet, DG
AU  - Jovanovic, A
AU  - Hughes, DA
AU  - Giugliani, R
AU  - Feldt-Rasmussen, U
AU  - Shankar, SP
AU  - Barisoni, L
AU  - Colvin, RB
AU  - Jennette, JC
AU  - Holdbrook, F
AU  - Mulberg, A
AU  - Castelli, JP
AU  - Skuban, N
AU  - Barth, JA
AU  - Nicholls, K
Y2  - 2020/12/17
Y1  - 2018/04/27
SN  - 1750-1172
UR  - http://hdl.handle.net/11343/255030
AB  - 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.
LA  - English
PB  - BMC
T1  - Migalastat improves diarrhea in patients with Fabry disease: clinical-biomarker correlations from the phase 3 FACETS trial
DO  - 10.1186/s13023-018-0813-7
IS  - Orphanet Journal of Rare Diseases
VL  - 13
IS  - 1
L1  - /bitstream/handle/11343/255030/PMC5923014.pdf?sequence=1&isAllowed=y
ER  -