Enzyme Replacement Therapy in Older Patients with Fabry Disease

San Diego—Despite enzyme replacement therapy, older patients in Canada with Fabry disease experience clinical events but seem to be living longer. That was among the findings of a comparison of outcomes of enzyme replacement therapy in patients >65 years of age compared with the overall Canadian Fabry Disease Initiative (CFDI) population. Michael L. West, BSc, FRCPC, FACP, and colleagues reported results of their study during a poster session at Kidney Week 2015. The poster was titled Outcomes of Patients over 65 in the Canadian Fabry Disease Initiative Study.

The CFDI is a multicenter prospective study of outcomes with enzyme replacement therapy in Fabry disease. Enzyme replacement therapy has been shown to reduce cardiac and renal disease associated with Fabry disease; however, there are few data on the benefits of enzyme replacement therapy in older patients.

The clinical status of patients enrolled in the CFDI is reviewed every 6 to 12 months. Enzyme replacement therapy is given every 2 weeks according to national guidelines with intravenous dose agalsidase alfa (0.2 mg/kg) or agalsidase beta (1.0 mg.kg). Cardiovascular outcomes are defined as stage 5 chronic kidney disease, stroke or transient ischemic attack, acute deafness, cardiac arrest, congestive heart failure, arrhythmia, unstable angina, myocardial infarction, percutaneous transluminal coronary angioplasty, pacemaker/implantable cardiovascular defibrillator, aortic valve replacement/coronary artery bypass grafting, and death.

Of the 429 subjects enrolled as of January 2015, 51 were >65 years of age, 68.6% were female, and 60.8% were on enzyme replacement therapy. Of the subjects >65 years of age, mean age was 71.8 years. There were no differences between those on enzyme replacement therapy and those not on enzyme replacement therapy in mean age, cardiac variant genotype, or time in the CFDI. Compared with those not on enzyme replacement therapy, those on enzyme replacement therapy had lower estimated glomerular filtration rate, greater proteinuria, and higher left ventricular myocardial infarction at baseline as well as 6 years later.

Three patients not on enzyme replacement therapy had five clinical events, prevalence 15%, and no deaths, with a clinical event rate of 1 per 34.5 patient years. Among those on enzyme replacement therapy, 20 had five deaths, 38 clinical events, prevalence 64.5%, and a clinical event rate of 1 per 9.3 patient years. Death was more likely in females versus males.

Patients >65 years of age had a greater prevalence of cardiac indications for enzyme replacement therapy compared with the overall CFDI population. Among those on enzyme replacement therapy, time to first clinical event was earlier than those not on enzyme replacement therapy (P=.003).

“Older patients with Fabry disease continue to have clinical events, mainly cardiac, despite enzyme replacement therapy but appear to be living longer. Use of the Canadian Fabry Disease guidelines appears to successfully target high-risk older patients. Enzyme replacement therapy used in this subgroup appears to be of benefit,” the researchers said.

Source: West ML, Bichet DG, Khan A, et al. Outcomes of patients over 65 in the Canadian Fabry Disease Initiative study. Abstract of a poster presented during American Society of Nephrology Kidney Week 2015, November 6, 2015, San Diego, California.

Funding for this study was provided by Genzyme, a Sanofi Company, Shire Inc., and non-US government support.