Patients with Fabry Disease after Enzyme Replacement Therapy Dose Reduction and Switch-2-Year Follow-Up.

ABSTRACT: Because of the shortage of agalsidase-? supply between 2009 and 2012, patients with Fabry disease either were treated with reduced doses or were switched to agalsidase-?. In this observational study, we assessed end organ damage and clinical symptoms with special focus on renal outcome after 2 years of dose-reduction and/or switch to agalsidase-?. A total of 89 adult patients with Fabry disease who had received agalsidase-? (1.0 mg/kg body wt) for >1 year were nonrandomly assigned to continue this treatment regimen (regular-dose group, n=24), to receive a reduced dose of 0.3-0.5 mg/kg and a subsequent switch to 0.2 mg/kg agalsidase-? (dose-reduction-switch group, n=28), or to directly switch to 0.2 mg/kg agalsidase-? (switch group, n=37) and were followed-up for 2 years. We assessed clinical events (death, myocardial infarction, severe arrhythmia, stroke, progression to ESRD), changes in cardiac and renal function, Fabry-related symptoms (pain, hypohidrosis, diarrhea), and disease severity scores. Determination of renal function by creatinine and cystatin C-based eGFR revealed decreasing eGFRs in the dose-reduction-switch group and the switch group. The Mainz Severity Score Index increased significantly in these two groups (P=0.02 and P<0.001, respectively), and higher frequencies of gastrointestinal pain occurred during follow-up. In conclusion, after 2 years of observation, all groups showed a stable clinical disease course with respect to serious clinical events. However, patients under agalsidase-? dose-reduction and switch or a direct switch to agalsidase-? showed a decline of renal function independent of the eGFR formula used.

SUBMITTER: Lenders M 

PROVIDER: S-EPMC4769208 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature