Maryam Banikazemi, MD; Jan Bultas, MD, PhD; Stephen Waldek, MB, BCh; William R. Wilcox, MD, PhD; Chester B. Whitley, PhD, MD; Marie McDonald, MD; Richard Finkel, MD; Seymour Packman, MD; Daniel G. Bichet, MD; David G. Warnock, MD; Robert J. Desnick, PhD, MD; Fabry Disease Clinical Trial Study Group*
Fabry disease is an X-linked storage disorder characterized by deficient lysosomal enzyme activity and excessive deposition of glycosphingolipids in vascular endothelial cells.
In this double-blind multicenter trial, 82 adults with kidney dysfunction from Fabry disease were randomly assigned to infusions of enzyme replacement with agalsidase beta or placebo every 2 weeks for up to 35 months. Agalsidase beta reduced the frequency of and delayed the time to clinical events (composite outcome of renal, cardiac, and cerebrovascular events and death) and caused infusion reactions more often than placebo.
Most clinical events in the small trial were worsening kidney function.
Agalsidase beta may slow disease progression in patients with advanced Fabry disease.
Dashed lines show Kaplan–Meier estimates of time to any clinical event (composite outcome). Solid lines show curves with adjustment for baseline proteinuria (urine protein–creatinine ratio), derived from a Cox regression analysis with baseline proteinuria added as a covariate to the regression equation (22, 23). Top. The time-to-event analyses for the composite end point for both treatment groups in the intention-to-treat population are shown. The unadjusted treatment-related hazard ratio associated with agalsidase beta was 0.57 (95% CI, 27.0 to 1.22; P = 0.14). With adjustment for baseline proteinuria, the hazard ratio was 0.47 (CI, 0.21 to 1.03; P = 0.06). Bottom. The time-to-event analyses for the composite end point for both treatment groups in the per-protocol population are shown. The unadjusted treatment-related hazard ratio associated with agalsidase beta was 0.54 (CI, 0.25 to 1.19; P = 0.12). With adjustment for baseline proteinuria, the hazard ratio was 0.39 (CI, 0.16 to 0.93; P = 0.034).
Proteinuria denotes the urine protein–creatinine ratio. The P values for formal tests for treatment interaction were as follows: baseline serum creatinine level, P = 0.16; baseline eGFR, P = 0.09; and baseline proteinuria, P = 0.54.
Data are shown as increases or decreases from baseline proteinuria (urinary protein–urinary creatinine ratio) for the placebo group (solid line) and the agalsidase-beta group (dashed line). A mixed model with fixed effects for treatment group, time, and treatment-by-time interactions, as well as random intercepts and slopes, for each patient over time was fit. The overall P value for treatment effect is 0.32.
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Banikazemi M, Bultas J, Waldek S, Wilcox WR, Whitley CB, McDonald M, et al. Agalsidase-Beta Therapy for Advanced Fabry Disease: A Randomized Trial. Ann Intern Med. 2007;146:77-86. doi: 10.7326/0003-4819-146-2-200701160-00148
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Published: Ann Intern Med. 2007;146(2):77-86.
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