Título

Renal and cardiac outcomes in female patients with Fabry disease treated with agalsidase beta: A Fabry Registry analysis of pre- versus post-treatment comparison

Introdução

Fabry disease is an X-linked disorder caused by GLA variants and cellular accumulation of glycolipids. The phenotypic spectrum in female patients is wide but few progress to end-stage renal disease compared with classic males.

Material e Método

This Fabry Registry analysis (NCT00196742) compared renal and cardiac outcomes pre- and post-treatment with agalsidase beta (AB, 1 mg/kg EOW) in adult female patients. Analyses included estimated glomerular filtration rate (eGFR, CKD-EPI equation), interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT). We included patients receiving AB ≥2 years, having ≥2 pre- and ≥2 post-AB records within –5/+5 years of AB initiation, excluding patients with dialysis or kidney transplant. GLA variants of patients were classic, unclassified (fabry-database.org), or had not been reported. Piece-wise mixed model was used to compare pre- vs. post-AB slopes. Effect modifiers included renal involvement (low [LRI] vs. high [HRI]) and renin–angiotensin system (RAS)-blocker use.

Resultados

The median first-AB age for 86 patients (53.5% classic) with eGFR assessments was 46.3 years (follow-up: pre-AB 3.6, post-AB 4.1 years). eGFR declined consistently within a normal range (<1 mL/min/1.73m2/year) pre- and post-AB without significant differences between slopes (slope difference = –0.13 mL/min/1.73m2/year, P-difference = 0.80). Different eGFR change patterns were found between groups of HRI/LRI (P-interaction = 0.0002) or ever/never RAS-blocker use (P-interaction = 0.066). The median first-AB age for 42 unique patients (50% classic) with cardiac wall thickness measures was 50 years (follow-up: pre-AB 3.5, post-AB 3.6 years). Compared to the significant increase during the pre-AB period, both LVPWT and IVST did not progress; pre- vs. post-AB slopes were significantly different for LVPWT (slope difference = –0.41 mm/year, P-difference = 0.0026) and approached significance for IVST (slope difference = –0.32 mm/year, P-difference = 0.068).

Discussão e Conclusões

Compared to the treatment-naïve period, overall eGFR decline remained unchanged after treatment with more prominent decline among females with more advanced renal involvement. Cardiac hypertrophy did not progress. Funding (Fabry Registry, abstract): Sanofi Genzyme.

These data were previously presented as an abstract and poster at the 15th Annual WORLDSymposium™ 2019, February 4–8, 2019, Orlando, FL, USA. Mol Genet Metab. 2019;126(2):S150. Abstract: 372

Palavras Chave

Agalsidase beta, Cardiac function, Fabry Registry, Females, GLA variants, Renal function