Fabry Stabilization index (FASTEX) is a valid, specific, and sensible instrument to accurately assess disease stability/progression in people with classic or non-classic Fabry disease, a large study showed.
The results highlighted the value of using this tool in the clinical setting to monitor Fabry patients in a standardized way.
The study, “New insights from the application of the FAbry STabilization indEX in a large population of Fabry cases,” was published in the Clinical Kidney Journal.
Fabry disease can cause damage to tissues and organs, including the nervous system, eyes, skin, gastrointestinal system, kidneys, and heart, and has a wide range of severity.
A clinical subdivision into “classic” and “non-classic or late onset” forms has been proposed to describe Fabry’s variability, in which the classic form develops early and affects patients more severely than non-classic Fabry disease.
Enzyme replacement therapy (ERT) — such as Replagal (agalsidase alpha) and Fabrazyme (agalsidase beta) — and chaperone therapy — such as Galafold (migalastat) — are approved treatments for Fabry disease that work by restoring the function of GLA, the enzyme that is deficient in Fabry patients. Only Fabrazyme is currently approved by the U.S. Food and Drug Administration.
However, there is still no validated, reliable, and standardized clinical tool to assess treatment responses in these patients. In accordance, a European expert consensus statement pointed out earlier this year the need to identify or develop objective measures to accurately assess disease stability/progression and treatment response rates in Fabry patients.
In 2016, Italian researchers developed a new index — FASTEX — to specifically monitor Fabry disease progression/stability, which was tested in 28 Fabry patients. The main differential feature of this index is the quantification of the disease’s stability or progression between two consecutive multidisciplinary evaluations through the analysis of a few specific parameters within three domains: nervous system, kidney, and heart.
The results led to the identification of a cutoff value of 20% to distinguish between stable and unstable patients, meaning that a patient showing an increase equal to or higher than 20% in the global FASTEX score between visits was considered clinically unstable.
Researchers in Italy have now evaluated the accuracy, sensitivity, and specificity of FASTEX in 132 patients (74 women and 58 men) with Fabry disease from nine Italian referral centers.
FASTEX was calculated by Ibis Informatica, an independent company, using patients’ clinical data of the latest follow-up multidisciplinary evaluation and the previous evaluation performed at least six to 12 months before. FASTEX results were compared to the treating physician’s independent clinical judgement on disease stability (stable or unstable) based on internationally accepted parameters regarding each affected organ.
Patients’ disease was classified as classic, non-classic, or unknown, based on their genetic mutations and associated disease form in the Fabry database.
Patients’ mean age was 46.3 years (46.8 in women and 45.8 in men), and 76.5% of patients showed classic Fabry disease, while 14.4% had the non-classic form. Ninety-nine patients were receiving ERT (Replagal, 58 patients; Fabrazyme, 38 patients) and three were being treated with Galafold; 33 were not receiving treatment.
The results showed that the FASTEX correctly identified 41 of 44 (93%) patients classified as unstable by physicians’ judgment and 80 of 88 (91%) of patients classified as stable by clinical judgment.
The data indicated that, compared to the treating physician’s clinical judgment, the FASTEX was able to accurately classify 121 of 132 (92%) patients on their disease stability/progression, even in a heterogeneous population of Fabry patients, with different genders, disease forms, and treatments (or treatment status).
Thus, the FASTEX is a reliable tool to assess disease progression or stability.
“The main advantage of the application of the FASTEX in routine clinical practice refers to the possibility of all physicians treating Fabry patients … having a standardized way to monitor the condition of Fabry patients, enabling the early detection of disease progression as well the assessment of disease stability or progression through periodic follow-up,” researchers stated.