Long-term follow-up of renal function in patients treated with migalastat for Fabry disease
Por:
Bichet, DG, Torra, R, Wallace, E, Hughes, D, Giugliani, R, Skuban, N, Krusinska, E, Feldt-Rasmussen, U, Schiffmann, R, Nicholls, K
Publicada:
1 sep 2021
Ahead of Print:
1 ago 2021
Resumen:
The effect of migalastat on long-term renal outcomes in enzyme replacement therapy (ERT)-naive and ERT-experienced patients with Fabry disease is not well defined. An integrated posthoc analysis of the phase 3 clinical trials and open-label extension studies was conducted to evaluate long-term changes in renal function in patients with Fabry disease and amenable GLA variants who were treated with migalastat for >= 2 years during these studies. The analysis included ERT-naive (n = 36 [23 females]; mean age 45 years; mean baseline estimated glomerular filtration rate (eGFR), 91.4 mL/min/mL/1.73 m(2)) and ERT-experienced (n = 42 [24 females]; mean age, 50 years; mean baseline eGFR, 89.2 mL/min/1.73m(2)) patients with amenable variants who received migalastat 123 mg every other day for >= 2 years. The annualized rate of change from baseline to last observation in estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR(CKD-EPI)) was calculated by both simple linear regression and a random coefficient model. In ERT-naive patients, mean annualized rates of change from baseline in eGFR(CKD-EPI) were -1.6 mL/min/1.73 m(2) overall and -1.8 mL/min/1.73 m(2) and -1.4 mL/min/1.73 m(2) in male and female patients, respectively, as estimated by simple linear regression. In ERT-experienced patients, mean annualized rates of change from baseline in eGFR(CKD-EPI) were -1.6 mL/min/1.73 m(2) overall and -2.6 mL/min/1.73 m(2) and -0.8 mL/min/1.73 m(2) in male and female patients, respectively. Mean annualized rate of change in eGFR(CKD-EPI) in ERT-naive patients with the classic phenotype (defined by white blood cell alpha galactosidase A [alpha-Gal A] activity of <3% of normal and multiorgan system involvement) was -1.7 mL/min/1.73 m(2). When calculated using the random coefficient model, which adjusted for sex, age, and baseline renal function, the annualized eGFR(CKD-EPI) change was minimal (mean: -0.1 and 0.1 mL/min/1.73 m(2) in ERT-naive and ERT-experienced patients, respectively). In conclusion, patients with Fabry disease and amenable GLA variants receiving long-term migalastat treatment (<8.6 years) maintained renal function irrespective of treatment status, sex, or phenotype.
Filiaciones:
Bichet, DG:
Univ Montreal, Dept Med, Hop Sacre Coeur, Montreal, PQ, Canada
Torra, R:
Univ Autonoma Barcelona, IIB St Pau, REDINREN, Inherited Renal Disorders,Nephrol Dept,Fundacio P, Barcelona, Spain
Wallace, E:
Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
Hughes, D:
Royal Free London NHS Fdn Trust, Lysosomal Storage Disorders Unit, London, England
UCL, London, England
Giugliani, R:
Fac Pharm UFRGS, Fac Med, Inst Basic Hlth Sci, Med Genet Serv,Dept Genet,Inst Biosci, Porto Alegre, RS, Brazil
Natl Inst Populat Med Genet INAGEMP, Porto Alegre, RS, Brazil
Skuban, N:
Amicus Therapeut Inc, Cranbury, NJ USA
Innocoll Pharmaceut, Newtown Sq, PA USA
Krusinska, E:
Amicus Therapeut Inc, Cranbury, NJ USA
Feldt-Rasmussen, U:
Univ Copenhagen, Natl Univ Hosp, Rigshosp, Dept Med Endocrinol & Metab, Copenhagen, Denmark
Schiffmann, R:
Baylor Scott & White Res Inst, Inst Metab Dis, Dallas, TX USA
Nicholls, K:
Univ Melbourne, Royal Melbourne Hosp, Dept Nephrol, Parkville, Vic, Australia
gold, Green Published
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