Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 68 |
| Journal | Orphanet Journal of Rare Diseases |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 27 2018 |
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Keywords
- Amenable mutation
- Diarrhea
- Fabry disease
- Gastrointestinal
- Globotriaosylceramide
- GSRS
- Lyso-Gb
- Migalastat
- Pharmacological chaperone
ASJC Scopus subject areas
- Genetics(clinical)
- Pharmacology (medical)
Cite this
Migalastat improves diarrhea in patients with Fabry disease : Clinical-biomarker correlations from the phase 3 FACETS trial. / Schiffmann, Raphael; Bichet, Daniel G.; Jovanovic, Ana; Hughes, Derralynn A.; Giugliani, Roberto; Feldt-Rasmussen, Ulla; Shankar, Suma; Barisoni, Laura; Colvin, Robert B.; Jennette, J. Charles; Holdbrook, Fred; Mulberg, Andrew; Castelli, Jeffrey P.; Skuban, Nina; Barth, Jay A.; Nicholls, Kathleen.
In: Orphanet Journal of Rare Diseases, Vol. 13, No. 1, 68, 27.04.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Migalastat improves diarrhea in patients with Fabry disease
T2 - Clinical-biomarker correlations from the phase 3 FACETS trial
AU - Schiffmann, Raphael
AU - Bichet, Daniel G.
AU - Jovanovic, Ana
AU - Hughes, Derralynn A.
AU - Giugliani, Roberto
AU - Feldt-Rasmussen, Ulla
AU - Shankar, Suma
AU - Barisoni, Laura
AU - Colvin, Robert B.
AU - Jennette, J. Charles
AU - Holdbrook, Fred
AU - Mulberg, Andrew
AU - Castelli, Jeffrey P.
AU - Skuban, Nina
AU - Barth, Jay A.
AU - Nicholls, Kathleen
PY - 2018/4/27
Y1 - 2018/4/27
N2 - 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.
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.
KW - Amenable mutation
KW - Diarrhea
KW - Fabry disease
KW - Gastrointestinal
KW - Globotriaosylceramide
KW - GSRS
KW - Lyso-Gb
KW - Migalastat
KW - Pharmacological chaperone
UR - http://www.scopus.com/inward/record.url?scp=85046266407&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85046266407&partnerID=8YFLogxK
U2 - 10.1186/s13023-018-0813-7
DO - 10.1186/s13023-018-0813-7
M3 - Article
C2 - 29703262
AN - SCOPUS:85046266407
VL - 13
JO - Orphanet Journal of Rare Diseases
JF - Orphanet Journal of Rare Diseases
SN - 1750-1172
IS - 1
M1 - 68
ER -