Long-term effectiveness of enzyme replacement therapy in Fabry disease: results from the NCS-LSD cohort study.

Abstract

OBJECTIVES:

To determine the effectiveness of enzyme replacement therapy (ERT) for adults and children with Fabry disease.

DESIGN:

Cohort study including prospective and retrospective clinical data. Age- and gender-adjusted treatment effects were estimated using generalised linear mixed models. Treated patients contributed data before and during treatment and untreated patients contributed natural history data.

PARTICIPANTS:

Consenting adults (N = 289) and children (N = 22) with a confirmed diagnosis of Fabry disease attending a specialist Lysosomal Storage Disorder treatment centre in England. At recruitment 211 adults and seven children were on ERT (range of treatment duration, 0 to 9.7 and 0 to 4.2 years respectively).

OUTCOME MEASURES:

Clinical outcomes chosen to reflect disease progression included left ventricular mass index (LVMI); proteinuria; estimated glomerular filtration rate (eGFR); pain; hearing and transient ischaemic attacks (TIA)/stroke.

RESULTS:

We found evidence of a statistically significant association between time on ERT and a small linear decrease in LVMI (p = 0.01); a reduction in the risk of proteinuria after adjusting for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (p < 0.001) and a small increase in eGFR in men and women without pre-treatment proteinuria (p = 0.01 and p < 0.001 respectively). The same analyses in children provided no statistically significant results. No associations between time on ERT and pain, risk of needing a hearing aid, or risk of stroke or TIAs, were found.

CONCLUSIONS:

These data provide some further evidence on the long-term effectiveness of ERT in adults with Fabry disease, but evidence of effectiveness could not be demonstrated in children.

• Authors: L J Anderson, K M Wyatt, W Henley, V Nikolaou, S Waldek, D A Hughes, G M Pastores, S Logan
• Journal: Journal of inherited metabolic disease (J Inherit Metab Dis) Vol. 37 Issue 6 Pg. 969-78 (Nov 2014) ISSN: 1573-2665 [Electronic] United States
• PMID: 24831586 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)

Chemical References

• alpha-Galactosidase

Topics

• Adolescent
• Adult
• Aged
• Child
• Child, Preschool
• Disease Progression
• England
• Enzyme Replacement Therapy (methods)
• Fabry Disease (complications, drug therapy)
• Female
• Glomerular Filtration Rate
• Heart Ventricles (anatomy & histology)
• Humans
• Infant
• Longitudinal Studies
• Male
• Middle Aged
• Prospective Studies
• Proteinuria (complications)
• Regression Analysis
• Retrospective Studies
• Stroke (complications)
• Treatment Outcome
• Young Adult
• alpha-Galactosidase (therapeutic use)