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<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.