Fabry Disease: Multidisciplinary Evaluation After 10 Years of Treatment with Agalsidase Beta

Abstract

Fabry disease is an X linked disorder of metabolism due to deficient a-galactosidase A activity. Enzyme replacement therapy (ERT) with agalsidase Beta was approved by EMA in FDA in 2003. Patients and methods: Six patients were enrolled. Baseline data was measured for renal, cardiac, and cerebrovascular functioning. We compared baseline quality of life scales with the current results. These parameters were assessed during the 10 years of follow-up period.Results: Before ERT four patients showed normal eGFR, one stage 2 of CKD, and one hyperfiltration stage. All presented microalbuminuria and just two cases showed proteinuria. After 10 years of ERT, no patient showed decrease in renal functioning. One patient decreased from proteinuria to microalbuminuria range. Before treatment one case showed left ventricular (LV) hypertrophy and LV Mass Index was abnormal in two female patients. After 10 years echocardiographic values did not present progression to LVH and one female showed regression to normal values of LV posterior wall and interventricular septum. Brain MRI showed ischemic lesions in one female and vertebrobasilar dolichoectasia in one male. From baseline and during the follow-up period MRI did not progress to new ischemic lesions and there were no clinical signs of cerebrovascular damage. After 10 years quality of life showed improvement in all domains measured.Conclusion: Early treatment of agalsidase Beta is related to a better outcome regarding stability and regression of signs and symptoms in Fabry disease. Our results in patients with mild organ involvement showed good outcomes and support an early and continuous ERT.

Long-term effectiveness of agalsidase alfa enzyme replacement in Fabry disease: A Fabry Outcome Survey analysis

“…A recent cohort study of adults in England by Anderson et al found that time on agalsidase alfa or agalsidase beta ERT was significantly associated with a reduction in LVMI as well as reduced risk of proteinuria and, among those without baseline proteinuria, a small increase in eGFR [28] . Another recent study by Juan et al of six patients in Argentina with mild disease at baseline found that after 10 years of agalsidase beta ERT, no patients had a reduction in eGFR or progression to LVH [29] . Results of other studies suggest that long-term agalsidase beta delays the time to morbidity and death [10] , [20] , although another study suggested no difference in event rate in patients with advanced disease at baseline versus an untreated control group [30] .…”

The effect of enzyme replacement therapy on clinical outcomes in male patients with Fabry disease: A systematic literature review by a European panel of experts

“…In MG populations, the observation that agalsidase beta had a stabilizing effect on eGFR was consistently reported in 12 publications (one RCT with open-label extension [149] and two further open-label extensions in the same patients [150,157] and one single-arm CT publication [152] and eight OS publications [159,163,165,175,177,180,181,188]). Two publications reported different effects of agalsidase beta dose reduction on eGFR: one OS publication reported a statistically significant decrease (105 patients followed for 8–16 months) [181], whereas an RCT observed no effect (52 patients followed for 12 months or longer) [176].…”

“…One OS publication reported a statistically significant decrease in proteinuria with agalsidase beta in combination with paricalcitol [188]. One open-label extension of a placebo-controlled RCT [157] and four OS publications [159,160,165,181] reported no statistically significant change in proteinuria or albuminuria. In an RCT [176] and another OS publication [181], agalsidase beta therapy at a dose of 0.2 mg/kg EOW or with a dose reduction to 0.3–0.5 mg/kg EOW did not result in statistically significant changes in proteinuria and albuminuria.…”

“…LVM was reported in one MG RCT [176], one MG single-arm CT publication [151] and 14 MG OS publications [[158], [159], [160], [161],[164], [165], [166], [167],169,170,173,174,179,180], half of which reported a statistically significant reduction in LVM with agalsidase beta. One of these noted a statistically significant decrease from baseline in LVM with ERT in patients without fibrosis, but no such effect in patients with mild or severe fibrosis [174].…”

“…One MG OS publication (in 25 patients followed for a median of 27 months) showed that, in younger patients (age <50 years), WMH remained stable in 44% of patients treated with agalsidase beta compared with 31% of patients receiving placebo [162]. Another MG OS reported no change in existing ischaemic brain lesions and no new brain lesions (in six patients followed for ≥120 months) [165].…”