European Experts Outline Organ-Specific Therapeutic Goals for Fabry Disease

A European panel of experts has defined a set of organ-specific therapeutic goals for Fabry disease, based on a systematic literature review and expert consensus.

These therapeutic goals are discussed in the study, “European expert consensus statement on therapeutic goals in Fabry disease,” recently published in Molecular Genetics and Metabolism.

Fabry disease is caused by the toxic accumulation of two fat molecules — globotriaosylceramide (Gb3) and lyso-Gb3 — in various tissues and organs, such as the heart, kidneys, nervous system, eyes, skin, bone, and lungs, which ultimately leads to tissue and organ damage.

The main complications of Fabry disease, including heart, kidney, and/or cerebrovascular disorders, which affect the the brain’s blood vessels or brain circulation — usually appear in adult patients, affecting their quality of life and increasing the risk of premature death.

“As our understanding of Fabry disease improves and treatment options expand, it is important to regularly re-evaluate and appraise the therapeutic goals for patients with Fabry disease,” the experts wrote in the study.

They defined detailed therapeutic goals for different levels of Gb3 and lyso-Gb3, which are disease biomarkers, and the involvement of the heart, kidneys, brain, and peripheral nervous system, the network of nerves that supply movement and sensation, as well as skin, eye, bone, and lung symptoms.

Suggested treatment strategies took into consideration differences in disease severity between patients; patients’ natural history, therapeutic responses, and negative burden; and the importance of multidisciplinary care.

Experts believe therapeutic approaches to Fabry disease should be multidisciplinary, and therapeutic goals should be tailored to each patient, depending on their characteristics, specific mutation, and disease stage.

After a confirmed diagnosis of Fabry disease, a detailed assessment of organ damage and disease-related symptoms should be performed to establish individualized and adequate therapeutic goals, as well as the most appropriate treatment plan. Regular monitoring is also crucial to review and optimize treatment.

Experts noted that optimal treatment strategies and disease management should include both early enzyme replacement therapy (ERT) and non-specific add-on treatments to control symptoms, prevent or minimize organ damage, and prevent the occurrence of damaging events, such as a stroke.

Reversal of symptoms or prevention of disease progression was considered the main therapeutic goal for most parameters associated with Fabry disease.

According to the consensus, medical teams should weigh a therapy’s expected clinical benefits with its potential therapy-related challenges to determine the best course of treatment. Improving patients’ quality of life was also considered fundamental, and can be achieved by managing pain, gastrointestinal symptoms, and psychological issues such as depression or anxiety.

Since there is increasing evidence that early ERT can potentially delay or prevent disease progression and permanent organ damage in Fabry disease patients, experts recommend beginning ERT as early as possible.

However, because some Fabry patients do not efficiently respond to ERT, the authors noted that additional research focusing on differential treatment responses, identification of objective measures to accurately assess response rates, and the effect of patients’ immune responses against ERT is necessary.

“These consensus recommendations help advance Fabry disease management by considering the balance between anticipated clinical benefits and potential therapy-related challenges in order to facilitate individualized treatment, optimize patient care and improve quality of life,” the authors concluded.

Of note, the authors disclosed the systematic literature review and meetings of the European expert panel were sponsored by Sanofi Genzyme.