What disease-specific therapies are available for patients with Fabry disease?
The long-term management of patients with Fabry disease includes timely treatment of symptoms and regular assessment of disease progression. The goal of Fabry disease treatment is to prevent irreversible tissue damage and organ failure. It is recommended that treatment assessments and follow-up visits are supervised by a physician experienced in Fabry disease, if possible, with input from a multidisciplinary team that includes a cardiologist, genetic counsellor, medical geneticist, nephrologist, neurologist, nurse and psychologist.1
Currently there are two intravenous enzyme replacement therapies available for the treatment of Fabry disease: agalsidase alfa and agalsidase beta.2,3 Additionally, one oral chaperone therapy, migalastat, is available for patients diagnosed with Fabry disease and who have an amenable variant.4 The availability of treatments differs between countries. For further information, please consult your local prescribing information.
The international PRoposing Early Disease Indicators for Clinical Tracking in Fabry Disease (PREDICT-FD) modified Delphi initiative (funded by Shire, now part of Takeda) aimed to determine when to initiate or stop Fabry disease-specific treatment (enzyme replacement therapy or chaperone therapy) in different patient groups in a variety of scenarios. According to expert consensus, Fabry disease-specific treatment should be initiated in5:
- All male patients aged ≥16 years with classical Fabry disease
- All male patients of any age with classical Fabry disease with indicators of early organ damage, irrespective of whether these symptoms meet the European Fabry Working Group (EFWG) recommendations for treatment initiation*
- All female patients with classical Fabry disease with symptoms meeting the EFWG recommendations for treatment initiation*
- All male and female patients with late-onset Fabry disease with symptoms meeting the EFWG recommendations for treatment initiation*
- Male or female patients with Fabry disease with evidence of damage to a single organ system, regardless of whether that organ system was being treated by a non-Fabry disease-specific therapy (e.g., cardiac pacemaker, kidney transplant or renal replacement therapy, etc.); Fabry disease-specific therapy should not be stopped in these patients, even if a non-Fabry disease-specific therapy becomes necessary
- Male or female patients with Fabry disease receiving multiple separate therapies for damage to multiple organ systems (e.g., combination of cardiac pacemaker, kidney transplant or renal replacement therapy, etc.); Fabry disease-specific therapy should not be stopped in these patients, even if a non-Fabry disease-specific therapy is required.
The panel agreed that Fabry disease-specific therapy should not be initiated in asymptomatic female patients with late-onset Fabry disease.5
*Consensus criteria for the initiation and withdrawal of enzyme replacement therapy were published in 2015 by the EFWG. The recommendations generally applied to males and females with classical Fabry disease and males with late-onset Fabry disease, and indicated that treatment should be initiated when clinical signs of central nervous system, heart or kidney involvement, gastrointestinal symptoms or pain first occur. It was also recommended that males aged ≤16 years with classical Fabry disease with no signs or symptoms of organ involvement and females with late-onset Fabry disease exhibiting early clinical disease signs could be considered for treatment initiation. The initiation and continuation of Fabry disease-specific treatment was suggested to be considered on an individual basis, and recommendations were made to not initiate treatment in some scenarios (e.g. patients with end-stage renal disease with no option of renal transplant, those with advanced heart failure or those with severe cognitive decline).5,6
How can patients with Fabry disease be monitored?
Following diagnosis, it is recommended that each organ system be comprehensively investigated in patients with Fabry disease. Patients should be monitored at relevant intervals, such that disease progression can be appropriately captured. For patients administered Fabry disease-specific therapy, it is recommended that the impact of treatment on all affected organ systems should be routinely assessed (Table 1).1
Recommendations for assessment and monitoring of organ systems in adult patients with Fabry disease. Reproduced with permission from Ortiz A et al. Mol Genet Metab 2018; 123: 416-427.1,8-13
What are the recommend therapeutic goals in patients with Fabry disease?
The main recommended therapeutic goals for patient management of Fabry disease are to optimise disease-specific and non-specific symptomatic treatments to prevent or minimise the effects of organ damage, prevent clinical events, and control symptoms. Published in 2018, organ-specific therapeutic goals were developed by a European group of experts and are shown in Table 2.14
Table 2. Recommended therapeutic goals for clinical manifestations of Fabry disease. Reproduced with permission from Wanner C et al. Mol Genet Metab 2018; 124: 189-203.14
C-ANPROM/INT/FAB/0017; Date of preparation: March 2021
- Ortiz A, Germain DP, Desnick RJ, et al. Fabry disease revisited: management and treatment recommendations for adult patients. Mol Genet Metab 2018; 123: 416-427.
- Sanofi Genzyme. Fabrazyme® EU Summary of Product Characteristics. Last updated November 2020.
- Shire Pharmaceuticals Ltd. Replagal® EU Summary of Product Characteristics. Last updated November 2020.
- Amicus Therapeutics Europe Ltd. Galafold® EU Summary of Product Characteristics. Last updated August 2020.
- Hughes DA, Aguiar P, Deegan PB, et al. Early indicators of disease progression in Fabry disease that may indicate the need for disease-specific treatment initiation: findings from the opinion-based PREDICT-FD modified Delphi consensus initiative. BMJ Open 2020; 10: e035182.
- Biegstraaten M, Arngrímsson R, Barbey F, et al. Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document. Orphanet J Rare Dis 2015; 10: 36.
- Germain DP, Fouilhoux A, Decramer S, et al. Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients. Clin Genet 2019; 96: 107-117.
- Arends M, Hollak CEM, Biegstraaten M. Quality of life in patients with Fabry disease: a systematic review of the literature. Orphanet J Rare Dis 2015; 10: 77.
- Authors/Task Force members, Elliott PM, Anastasakis A, et al. 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J 2014; 35: 2733-2779.
- Weidemann F, Maier SKG, Störk S, et al. Usefulness of an implantable loop recorder to detect clinically relevant arrhythmias in patients with advanced Fabry cardiomyopathy. Am J Cardiol 2016; 118: 264-274.
- Eng CM, Germain DP, Banikazemi M, et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 2006; 8: 539-548.
- Kolodny E, Fellgiebel A, Hilz MA, et al. Cerebrovascular involvement in Fabry disease. Stroke 2015; 46: 302-313.
- Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl 2013; 3: 1-150.
- Wanner C, Arad M, Baron R, et al. European expert consensus statement on therapeutic goals in Fabry disease. Mol Genet Metab 2018; 124: 189-203.