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2021 is the 20th year of the Fabre Disease Ends Survey (FOS) study. spans 20 years, and FOS research has achieved fruitful results!
FOS study is an international multicenter, observational, and registered study that collects data on long-term clinical outcomes and safety of patients treated with untreated or with agasase alpha, aims to expand understanding of FD and improve patient clinical management.
was admitted to the first patient since 2001. As of January 2021, a total of 4,484 patients from 26 countries and 144 centers participated in the FOS study. The research results involved multiple aspects of Fabre disease.
In this issue, we will review the important clinical progress of FOS research in 20 years.
Progress 1: Based on FOS research, three Fabre disease evaluation tools were developed
3 disease evaluation tools involved the severity of Fabre disease and the prognosis of disease, providing powerful tools for disease research, including: FOS Mainz Severity Score Index (FOS-MSSI), Fabre Disease International Prognostic Index (FIPI) and Fabre Disease Specific Children's Health and Pain Questionnaire (FPHPQ). See Table 1[1] for details.
Table 1. Fabre disease evaluation tool and significance
Progress 2: Clarify the characteristics and progress of Fabre disease
FOS research data analyzes the progress of Fabre disease and the impact of treatment on disease progression. Fabre disease involves the nervous system, , skin, kidney, heart, hearing, blood vessels, cerebrovascular, gastrointestinal tract and eye organs or systems. Signs and symptoms may include neuropathic pain, angina keratoma, , proteinuria, angina and dyspnea, gastrointestinal symptoms, cerebrovascular events or tinnitus, and vertigo.
The first batch of studies analyzed baseline data from 366 patients from 11 countries. The results showed that there was a long delay between the onset of symptoms and diagnosis of patients, 13.7 years for male patients and 16.6 years for female patients. About 25% of FOS registered patients are misdiagnosed with rheumatism, neuropsychiatric diseases, orthopedic diseases, kidney disease and coronary artery disease [1]. In 2017, data analysis of 598 patients with Fabre disease found that compared with 2001-2006, the median time from diagnosis to initiation of treatment was shortened between 2007-2013 (adult: 2.1 vs 0.9, P <> Figure 1) [2].
Figure 1. Investigation data on the onset of Fabre disease in adults and pediatric patients, delayed diagnosis and delayed treatment time
Progress 3: Confirmed the clinical benefit of starting ERT treatment as early as possible
More than FOS studies ( Table 2) confirmed from different dimensions that timely enzyme replacement therapy (ERT) treatment can reduce the risk of cardiovascular and renal events.
Hughes D et al. published in 2021 shows that compared with delayed treatment, whether it is timely treatment after symptoms appear or timely treatment after diagnosis, it can significantly reduce the risk of cardiovascular and renal events [3].
In another age-strength analysis: ERT started at ≤18 years old, which can slow down the progression of renal disease and cardiomyopathy of ; ERT started at 18-30 years old, which is estimated to have significantly worsened glomerular filtration rate (eGFR); while ERT started at >30 years old, eGFR and left ventricular mass index (LVMI) were significantly worsened [4].
When ERT is initiated, what is the effect of baseline cardiorenal involvement status on the treatment outcome of ERT? Analysis of different subgroups of LVMI and eGFR in the FOS study showed that patients with left ventricular hypertrophy (LVH) and eGFR <>
Table 2. Clinical outcomes of early vs delayed ERT treatment in patients with Fabre disease
Progress 4: Confirm the effectiveness and safety of long-term ERT treatment
High-term safety and effectiveness of ERT in children and adults [1]. In the 10-year follow-up analysis of the
FOS study, the eGFR in women was relatively stable, with a slight decrease in men. The LVMI in patients without LVH was stable at baseline, and the LVMI in patients with LVH was slightly increased at baseline, indicating that ERT treatment can stabilize cardiorenal function during treatment up to 10 years [6].In the 20-year follow-up analysis of the
FOS study (n=580), the median LVMI and eGFR at baseline were 49.3 g/m2.7 and 98.1 mL/min/1.73 m, respectively. The annual change rate of LVMI (±SE) in the ERT treatment group was +0.4 (0.08) g/m2.7, showing a slight increase, and the eGFR change rate was –1.6 (0.09) mL/min/1.73 m, with a slight decrease, suggesting that long-term treatment of agasase α can stabilize the heart and renal function of patients with Fabre disease ( Fig. 2) [7].
Figure 2. The mean slope of LVMI (upper side) and eGFR (lower side) of the 20-year follow-up ERT treatment group changes over time
Total
junction
20 journey review, FOS research provides basic data and evaluation tools for Fabre disease, improves Fabre disease management, expands the understanding of the disease, and confirms the clinical benefits of early and long-term ERT treatment.
In the future, we look forward to the success of FOS research.
References:
[1]Michael Beck, et al.Orphatnet J Rare Dis.2022 Jun 20;17(1)238.
[2]Reisin R, et al.Int J Clin Pract.2017;71(1):12914.
[3]Hughes D, et al.Drug Des Devel Ther.2021;15:3561–72.
[4]Parini R, et al.Drug Des Devel Ther.2020;14:2149–58
[5]Feriozzi S,et al.Clin Ther.2020 Dec;42(12):2321-2330.e0.
[6]Ramaswami U,et al.Drug Des Devel Ther.2019,13:3705-3715
[7]Beck M,et al.Molecular Genetics and Metabolism.2021;132(2):S19.
Small survey
Approval number: VV-MEDMAT-76023
Approval time: 10/10/2022
Expiry time: 10/9/2024
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