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

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?p?=?0.01 and p?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.