A new evaluation tool, the FAbry STabilization indEX (Fastex), can help detect disease progression in individuals with Fabry disease, and could become useful in routine practice and clinical trial assessments.
The tool was described in a paper, titled “FAbry STabilization indEX (FASTEX): Clinical evaluation of disease progression in Fabry patients,” published in Molecular Genetics and Metabolism.
Fabry disease is a rare genetic disease caused by mutations in the GLA gene, which results in the accumulation of fat substances such as globotriaosylceramide (Gb3) or globotriaosylsphingosine (lyso-Gb3) inside cells, leading to tissue and organ damage.
Quantifying disease burden in Fabry disease can help inform decisions about treatment, and demonstrate efficacy in clinical trials.
Currently, two tools commonly used for this purpose are the Mainz Severity Score Index (MSSI) and the Fabry disease severity scoring system (DS3). Both evaluate disease activity in several domains (impact on the heart or kidneys, for instance) to provide a snapshot of disease severity.
Although these tools can assess severity in an individual compared with the overall patient population, they are less able to detect change in an individual’s disease state over time.
“The primary aim of MSSI and DS3 is the assessment of a disease load, necessitating important clinical alterations between two visits and/or large population in cohort studies to detect significant changes over time,” the researchers wrote.
“Hence, it is proposed that a dynamic, simpler and faster tool that directly determines a disease stability or progression might be more suitable for the clinical routine as well as for cohort studies aiming to analyze therapeutic effects than a static score.”
Fastex is a publicly-available tool with fewer items (seven) than the MSSI (with 24) and DS3 (12). It looks at three domains: the nervous system, kidneys, and heart. Because it doesn’t include many factors that are unlikely to change over time (e.g. the presence of cornea verticillata or angiokeratoma), Fastex may be more sensitive to changes in disease state than the MSSI or DS3.
In the new study, 62 people (28 female, average age 49 years) with Fabry disease underwent two clinical examinations that included evaluation with the MSSI, DS3, and Fastex. The evaluations were done one year apart, during which time all participants were treated with enzyme replacement therapy (ERT; i.e. Galafold or Fabrazyme). Of note, 15 patients who had never received ERT at the beginning of the study (baseline) subsequently initiated treatment.
Overall, Fastex scores correlated closely with both MSSI and DS3 scores, though the two latter scores correlated more closely with each other. This was expected, suggesting that all three tools are measuring similar features.
Interestingly, MSSI and DS3 scores in patients who had never received treatment at baseline correlated significantly with levels of lyso-Gb3 although Fastex scores did not.
The researchers then looked at changes in these scores over time. Participants were analyzed separately based on which ERT they had been given, and whether they had just started the therapy or had been on it for some time. In all cases, MSSI and DS3 scores did not change over time.
However, Fastex scores changed significantly for more than half of the participants. The researchers defined progression (sometimes referred to as having “unstable disease”) as a change in at least 20% in Fastex scores. Based on this definition, 41 (66%) participants experienced disease progression over the course of the year assessed.
In all participants, no significant differences were observed in age, sex, or treatment modality (including both types of ERT and treatment length), or in terms of heart and kidney involvement at the start of the year.
Closer analysis of the unstable disease group revealed that the change in scores was driven primarily by changes in kidney parameters over the year.
“With respect to our current data,” the researchers wrote, “we conclude that the MSSI and DS3 scores are applicable to determine the general disease burden in affected patients especially at the time point of diagnosis. By contrast, the Fastex score seems to be a better tool and more sensitive to assess stability or disease progression over time compared to MSSI and DS3.”