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Safety analysis of self-administered enzyme replacement therapy using data from the Fabry Outcome and Gaucher Outcome Surveys

Orphanet Journal of Rare Diseases volume 20, Article number: 145 (2025) Cite this article

Abstract

Background

Fabry disease and Gaucher disease are rare genetic disorders characterized by defective degradation of glycosphingolipids caused by enzymatic deficiencies in α–galactosidase A and β–glucocerebrosidase, respectively, and often require life-long treatment. Treatment options for these disorders include replacing the deficient enzymes via enzyme replacement therapy (ERT). Agalsidase alfa for Fabry disease and velaglucerase alfa for Gaucher disease are two ERT options with demonstrated efficacy, safety, and tolerability. ERT infusions administered by a health care provider (HCP) in the clinic/hospital, or at the patient’s home are considered HCP-supported infusions. Self-administration of ERT (by patient, partner, relative, or caregiver) is optional in patients who tolerate the HCP-supported infusions at home and have a suitable home environment. This analysis explored the safety profiles of self-administered agalsidase alfa (202 patients) and velaglucerase alfa (30 patients) versus HCP-supported infusions using data from the Fabry Outcome Survey (FOS) and Gaucher Outcome Survey (GOS) registries.

Results

The frequency of infusion-related reactions (IRRs) adverse events (AEs) recorded in the two registries was lower in patients self-administering (FOS: 4.5%, GOS: 0%) versus patients receiving HCP-supported infusions (FOS: 13.6%, GOS: 1.6%). In the FOS registry, AE rates per 100 patient-years (100PY) of follow-up were similar between the self-administration (7.99) and HCP-supported infusion (6.78) groups. In patients self-administering agalsidase alfa, cardiac disorders were the most frequently reported AEs (19 [9.4%] patients) and serious AEs (12 [5.9%]) and gastrointestinal disorders were the most frequently reported IRRs (3 [1.5%]). In the GOS registry, AE rates per 100PY were similar between self-administration (4.97) and HCP-supported infusion (4.67) groups. In patients self-administering velaglucerase alfa, skin and subcutaneous disorders (4 [13.3%]) and infections and infestations (2 [6.7%]) were the most reported AEs and serious AEs, respectively, and no IRRs were reported.

Conclusions

These findings suggest that self-administration of agalsidase alfa or velaglucerase alfa infusions are not associated with additional safety risks compared with HCP-supported infusions and are a suitable option for qualifying patients. Further research is warranted to support these findings and to explore further the long-term safety and efficacy of ERT self-administration.

FOS trial registration: ClinicalTrials.gov, NCT03289065. Registered 01 April 2001, https://clinicaltrials.gov/study/NCT03289065. GOS trial registration: ClinicalTrials.gov, NCT03291223. Registered 27 July 2010, https://classic.clinicaltrials.gov/ct2/show/NCT03291223.

Background

Fabry disease and Gaucher disease are rare genetic lysosomal storage disorders characterized by defective degradation of glycosphingolipids due to enzymatic deficiencies in α–galactosidase A and β–glucocerebrosidase, respectively [1, 2]. Patients with Fabry disease suffer from progressive damage to renal, cardiac, and central nervous systems, and report recurrent episodes of neuropathic pain and gastrointestinal disturbance [3, 4]. There are two recognized forms of Fabry disease (classical and late-onset). Classical Fabry disease usually starts in childhood or adolescence with symptoms occurring earlier in males compared with females [5, 6]. Renal, cardiovascular, or cerebrovascular complications may lead to premature death in patients with untreated classical Fabry disease [3, 7]. Late-onset Fabry disease generally starts after age 30 and has a more variable disease course that is less severe, with disease manifestations sometimes limited to a single organ [8].

Symptoms of Gaucher disease include anemia, thrombocytopenia, hepatosplenomegaly, and skeletal complications [9], with age of onset and life expectancy varying according to disease type and severity. Type I, the most common form in Europe and the United States, is not associated with central neurological impairment, except for the predisposition of these patients to develop Parkinson’s disease, and may present at any stage of life [10, 11]. Types II and III are associated with neurological abnormalities, which are more severe in type II [11]. Type II regularly presents before the age of 6 months and is often fatal in infancy [11], while type III typically presents prior to age 20 with life expectancy ranging from adolescence to the fifth decade of life [11, 12].

Currently available treatment options for Fabry disease include three enzyme replacement therapy (ERT) agents (agalsidase alfa [not available in the United States], agalsidase beta, and pegunigalsidase alfa) and one oral pharmacological chaperone (migalastat, only for patients with amenable mutations) [13, 14]. For Gaucher disease, three ERTs (imiglucerase, velaglucerase alfa, and taliglucerase alfa [not available in the European Union]) and two oral substrate reduction therapies (miglustat and eliglustat) are available [15]. For patients with clinically relevant manifestations of Fabry or Gaucher disease, management is focused on replacing the deficient enzymes via ERT, oral pharmacological chaperone therapy (Fabry) or substrate reduction therapy (Gaucher). ERT has demonstrated efficacy through control of symptom progression, and acceptable safety and tolerability profiles in real-world studies for both Fabry [16, 17] and Gaucher [18, 19] diseases. In many countries, initial ERT infusions typically occur in a clinical/hospital setting and, once initiated, may be life-long [20, 21]. While ERT is effective, it may not address all disease manifestations in part due to the pharmacodynamics and biodistribution of enzymes [22], and in some cases where manifestations were already irreversible at the start of therapy.

ERT infusions can be administered by a health care provider (HCP) in the clinic/hospital, as described, or at the patient’s home, both of which are considered HCP-supported infusions. Home infusion by an HCP of agalsidase alfa (for Fabry disease) [23, 24] or velaglucerase alfa (for Gaucher disease) [9, 25] is an established option in some countries for patients who tolerate it and have a suitable home environment. Factors for establishing home infusions can include, but are not limited to, completion of a required number of in-clinic/hospital infusions, no infusion-related reactions (IRRs), appropriate conditions for receiving and storing the medicinal product to infuse at home, and an overall safety and risk assessment by the HCP prior to initiating home treatment. Home infusions are defined as administration of the infusion to a patient at home and solely relate to the location for the infusion to be performed and do not refer to who administers the infusion. Home infusions of agalsidase alfa and velaglucerase alfa have been associated with improvements in patient satisfaction and quality of life (QoL), compared with infusions in a clinic/hospital setting [26,27,28,29], and with treatment adherence greater than 97% [30, 31]. Additionally, home infusion has the potential to reduce the risk of hospital acquired infection, including COVID-19 [32, 33].

Patients tolerating infusions administered by an HCP at home may be eligible to self-administer treatment, or have treatment administered by their partners/relatives, with sufficient training [24, 28]. This training typically includes good hygiene practices, safe reconstitution, cannulation, administration, and disposal of ERT as observed by an HCP [24, 25, 28]. Self-administration is defined as administration of the ERT infusion via intravenous cannula either by the patient (self), parent, relative, or caregiver under the supervision of a physician (who may not be present on site). Self-administration can be performed by using a butterfly needle to access peripheral veins, or if needed, by using a fully implanted venous device (e.g., port-a-cath) [24, 28]. Patients are required to report any adverse reaction that may occur during or after each infusion [24, 28]. If the infusion is administered by the patient, a responsible adult must be present on-site and available to help in case of an emergency. The potential transition of patients between receiving HCP-supported ERT infusions to self-administering ERT infusions is shown in Fig. 1. Successful self-administration programs have been implemented for several conditions including multifocal motor neuropathy [34], hereditary angioedema [35, 36], and hemophilia [37] with no safety concerns in excess of those seen in the clinic setting. Due to the life-long nature of therapy for Fabry and Gaucher diseases, self-infusion at home may be desirable.

Fig. 1
figure 1

Patient transitions between HCP-supported and self-administered ERT infusions. In HCP-supported infusions, patients receive ERT infusions administered by an HCP in the clinic, hospital, or in the patient’s home. Patients can then transition to self-administering ERT infusions where either the patient (self), partner, relative, or caregiver administers the infusion in the patient’s home. Bidirectional dashed arrows indicate that a patient may transition from one therapy option to another, especially when an adverse event is experienced, and most patients return to the clinic/hospital for their next infusion following an adverse event. ERT, enzyme replacement therapy; HCP, health care provider

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The objective of this analysis was to explore the safety profiles of agalsidase alfa and velaglucerase alfa when self-administered by the patients (or their partners/relatives) compared with HCP-supported infusions using data from the Fabry Outcome Survey (FOS) and Gaucher Outcome Survey (GOS) registries.

Methods

Study design and data sources

This international, multicenter, observational analysis examined patient data reported in the FOS (NCT03289065; https://clinicaltrials.gov/study/NCT03289065) [13] and GOS (NCT03291223; https://classic.clinicaltrials.gov/ct2/show/NCT03291223) [38] registries, sponsored by Shire Human Genetic Therapies, Inc., a Takeda company. The date of registration for FOS (NCT13289065) was April 1, 2001 and for GOS (NCT03291223) was July 27, 2010. The primary aims of the FOS and GOS registries are to provide long-term data on the effectiveness and safety of ERT for Fabry disease and Gaucher disease, respectively, broaden the understanding of each condition, and improve the clinical management of affected patients.

FOS and GOS registries have been approved by the ethics institutional review boards of participating centers and are conducted in compliance with relevant global and local regulations and best practices, Good Pharmacoepidemiological Practice, Good Research for Comparative Effectiveness principles, and the relevant principles of the International Conference on Harmonisation Good Clinical Practice guidelines, sixth edition (ICH E6), as appropriate for an observational registry. All participants provided written informed consent.

Population

Patients enrolled in FOS or GOS with a confirmed diagnosis of Fabry disease or Gaucher disease who received ≥ 1 dose of study drug were eligible for inclusion. The self-administration populations included: patients enrolled in the FOS registry who self-administered ≥ 1 dose of agalsidase alfa with a confirmed Informed Consent Form (ICF) as of January 7, 2021; patients enrolled in the GOS registry who self-administered ≥ 1 dose of velaglucerase alfa with confirmed ICF as of July 30, 2021. Patients with missing start dates for self-administration were excluded from the analysis, while those with missing end dates were assumed to be continuing self-administered infusions, unless withdrawn from the registry.

Self-administration was defined as administration of ERT infusion via intravenous cannula either by the patient (self), partner, relative, or caregiver under the supervision of a physician (who may not be present on site) in the patient’s home. If the infusion was administered by the patient, a responsible adult was required to be present on-site and available to help in case of an emergency. Home infusion was defined as the administration of ERT infusion to a patient at home, was solely related to the location of the infusion, and did not refer to who administered the infusion. Patients who received home therapy with ERT infusions administered by an HCP regardless of location were not included in the self-administration populations. The populations who received HCP-supported infusions included patients enrolled in FOS or GOS who received ≥ 1 dose of study drug administered by HCP in the clinic, hospital, or at the patient’s home. The general practices of home therapy, self-administration, and approaches to patient training differed among the individual countries included in this analysis (Table 1).

Table 1 Home administration practices per country
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Data collection and analyses

Data on patient demographics, study drug administration, drug exposure, and adverse events (AEs) were collected at the time of registry entry via the electronic case report form. All available data to January 7, 2021 (FOS) or July 30, 2021 (GOS) were included in the analysis. AEs (regardless of relationship to treatment) with a start date on or after the first self-administered infusion and no later than the last known date of self-administered infusion were reported as being associated with self-administration. All other AEs (regardless of relationship to treatment) were reported as being associated with HCP-supported infusions.

For self-administrations reported in FOS and GOS, exposure to ERT was calculated from dates of first and last self-administered infusions. For HCP-supported infusions, exposure to ERT was calculated from the date of first infusion to the data extract date or to the date of drug discontinuation in both FOS and GOS. For patients who received HCP-supported infusions followed by self-administering infusions, the HCP-supported infusion exposure to ERT was calculated from date of first infusion to start date of self-administration. The total number of infusions per patient per year was derived from an assumed 26 infusions per year based on every other week dosing.

Results

Patient demographics

In total, 232 patients received ≥ 1 self-administered dose of ERT and were included in the self-administration analysis populations: 202 from FOS and 30 from GOS. Of the 202 patients who self-administered agalsidase alfa, 153 (75.7%) were from the Netherlands or the United Kingdom. Of all patients who received agalsidase alfa in the Netherlands and the United Kingdom, 84.6% and 28.3%, respectively, were self-administering infusions. Of the 30 patients who self-administered velaglucerase alfa, 11 (36.7%) were from Israel and 19 (63.3%) were from the United Kingdom. Of all patients who received velaglucerase alfa in Israel and the United Kingdom, 3.6% and 23.2%, respectively, were self-administering infusions. A total of 2233 patients in FOS and 784 patients in GOS received in-clinic/hospital or HCP-supported home infusions only and were included in this analysis as patients who received ERT infusions in an HCP-supported setting. Baseline characteristics of patients self-administering ERT at home and those receiving HCP-supported ERT infusions were generally well balanced across groups, except for age at diagnosis in patients who received velaglucerase alfa, with patients in the self-administration group diagnosed younger than patients in the HCP-supported group (Table 2).

Table 2 Patient demographics and characteristics
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The type of Gaucher disease diagnosed was known for all 30 patients self-administering ERT and for 769 patients receiving HCP-supported infusions. Most patients had type I Gaucher disease with similar proportions in both groups (28 [93.3%] patients in the self-administration group and 741 [96.4%] patients in the HCP-supported group). In the self-administration group, no patients had type II Gaucher disease, and 2 (6.7%) patients had type III Gaucher disease. In the HCP-supported group, 2 (0.3%) patients had type II Gaucher disease, and 26 (3.4%) patients had type III Gaucher disease.

Safety

Data from the FOS registry suggest AEs were proportionally less frequently reported in patients who, after initiating infusion of agalsidase alfa in a clinic/hospital setting, went on to self-administer treatment compared with patients who received HCP-supported infusions of treatment (28.2% vs 57.0%, respectively) (Table 3). However, AE rates per 100 patient-years (100PY) of follow-up were similar between the self-administration and HCP-supported groups (7.99 vs 6.78, respectively). The most frequently reported AEs and serious AEs experienced by patients self-administering agalsidase alfa were cardiac disorders, affecting 19 (9.4%) and 12 (5.9%) patients, respectively. An important point for consideration is that the serious AEs reported are most likely associated with Fabry disease itself rather than the ERT. The drug-related AE rate per 100PY was 1.81 for agalsidase alfa. Drug-related and serious AEs were proportionally less frequently reported with self-administered versus HCP-supported infusions with agalsidase alfa. The frequency of recorded IRRs AEs was lower in patients self-administering (4.5%,) versus patients receiving HCP-supported infusions (13.6%). The most reported IRRs by patients self-administering agalsidase alfa were gastrointestinal disorders, affecting 3 (1.5%) patients, while the most reported IRRs in patients receiving HCP-supported infusions were general disorders and administration site conditions affecting 133 (5.5%) patients.

Table 3 Summary of adverse eventsa
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In the self-administration population, one patient had two reported drug-related serious AEs of paranoia and abnormal behavior, and another patient had one reported drug-related serious AE of myocardial infarction. No AEs in the self-administration group led to discontinuation whereas 30 (1.2%) patients in the HCP-supported group discontinued agalsidase alfa infusions. No patients died from AEs in the self-administration group, while 193 (7.9%) patients died from serious AEs (not related to the infusion) in the group receiving HCP-supported infusions. Of these, 5 (0.2%) patient deaths were possibly related to agalsidase alfa, and the remaining 188 deaths were considered unrelated to treatment. The possibly treatment-related but not IRRs fatal AEs (8 events) were abnormal hepatic function, acute cardiac failure, arrhythmia, cerebral infarction, decreased platelet count, pulmonary oedema, septic shock, and sudden death. The mean times from starting self-administration to the first treatment-emergent AE (regardless of relationship to treatment), serious AE (regardless of relationship to treatment), and IRR were 2.6 years, 3.0 years, and 2.9 years, respectively. For HCP-supported infusions, the mean times from starting ERT to first non-serious AE, serious AE, and IRR were 2.9 years, 4.2 years, and 2.1 years, respectively.

Data from the GOS registry suggest the proportion of patients who reported any AE with velaglucerase alfa self-administration was slightly higher compared with patients who received HCP-supported infusions (40.0% vs 33.3%, respectively). However, AE rates per 100PY were similar between groups (4.97 vs 4.67, respectively). Lower or similar proportions of patients experienced drug-related, serious, or fatal AEs, or IRRs (Table 3), with a drug-related AE rate of 0.22 per 100PY for velaglucerase alfa. The most frequently reported AEs and serious AEs experienced by patients self-administering velaglucerase alfa were skin and subcutaneous disorders (4 [13.3%] patients) and infections (2 [6.7%] patients), respectively. Patients self-administering velaglucerase alfa reported no IRRs versus 1.6% of patients receiving HCP-supported infusions. The most reported IRRs in patients receiving HCP-supported infusions, were injury, poisoning, and procedural complications, affecting 6 (0.7%) patients.

In the self-administration group, one (3.3%) patient died from cardiac arrest deemed unrelated to velaglucerase alfa after 8.2 years of self-administering infusions. In the group receiving HCP-supported infusions, 31 (3.8%) patients died from AEs, and none were considered related to velaglucerase alfa. No AEs in the self-administration group led to discontinuation, whereas 5 (0.6%) patients in the HCP-supported group discontinued velaglucerase alfa infusions. The mean times from starting self-administration to first treatment-emergent AE (regardless of relationship to treatment) and serious AE (regardless of relationship to treatment) were 4.6 years and 4.5 years, respectively. For HCP-supported infusions, the mean times from starting ERT to first non-serious AE, serious AE, and IRR were 4.9 years, 4.7 years, and 2.6 years, respectively.

Discussion

The results of this analysis from the FOS and GOS registries support that there are no additional safety concerns with self-administration of the ERTs agalsidase alfa or velaglucerase alfa versus HCP-supported infusions. The frequency of IRRs and drug-related AEs was similar or lower in the self-administration groups compared with those receiving HCP-supported infusions. The proportion of patients self-administering treatment who had AEs was relatively low, and the overall proportion of patients reporting serious AEs was lower with self-administration of ERT versus receiving HCP-supported ERT infusions. This may be attributed to a combination of factors, including the return of patients who experience an IRR or AE to receiving HCP-supported infusions in the clinic/hospital setting, switching to self-administration after no observed IRRs or AEs with HCP-supported infusions, the high familiarity of patients with these ERTs, and their favorable safety profiles. Drug-related serious AEs in patients self-administering ERT were infrequent, with a total of three events reported as drug-related by two patients self-administering agalsidase alfa (paranoia and abnormal behavior in one patient, and myocardial infarction in another patient) and none reported by patients self-administering velaglucerase alfa.

The follow-up period for patients self-administering ERTs was shorter and hence AEs were recorded over a shorter time-period compared with follow-up time for AEs in patients receiving HCP-supported infusions. However, adjusting the AE rates per 100PY for both agalsidase alfa and velaglucerase alfa resulted in similar rates between the self-administration and HCP-supported infusion populations, indicating that the frequency of AEs was similar in both groups. The long mean time to first treatment-emergent AE from the start of self-administration of both agalsidase alfa and velaglucerase alfa suggests that AEs are not likely to arise from inadequate training or poor infusion practices. Further, patients self-administering agalsidase alfa and velaglucerase alfa have been doing so successfully over a number of years with both ERTs.

Comparisons of patients self-administering ERT infusions with patients receiving HCP-supported infusions need to be interpreted with caution owing to certain differences between these populations. Firstly, all patients start treatment in the clinic/hospital and self-administration programs are recommended only for patients who have been shown to tolerate HCP-supported infusions well. Secondly, before transitioning to self-administration and under the responsibility of the treating physician, patients must complete the required number of HCP-supported infusions, which varies between countries. Thirdly, AEs were recorded over a shorter time-period for patients self-administering infusions than for those receiving HCP-supported infusions. Nonetheless, the results of our analysis suggest that self-administration of agalsidase alfa and velaglucerase alfa has a favorable safety profile and can be a suitable option for many patients. Indeed, this evaluation of data from the FOS and GOS patient registries revealed that self-administration of ERT is already being practiced successfully in several countries worldwide.

Home administration by HCPs of ERT with agalsidase alfa or velaglucerase alfa has been shown to improve satisfaction, convenience, and QoL of patients [30, 31]. Additionally, ERT home administration frees up time and space in the clinic, which is of benefit to HCPs. Further, transitioning to self-administration of ERT affords both patients and HCPs the convenience of not traveling to and from the patient’s home, cost-saving advantages and reduces the impact of travel on the environment overall contributing to treatment sustainability. Self-administration practices, where agalsidase alfa and velaglucerase alfa infusions are managed by the patient, provide independence and control to choose a time of administration that is convenient. Further, self-administering infusions allows patients to contribute to and manage their own care. Notably, during the COVID-19 pandemic, patients who were already self-administering ERT did not have to stop infusions or have their regimen disrupted; they benefited from being able to continue treatment in the comfort and safety of their own home, without the risk of exposure to HCP personnel [32, 39].

This study had some limitations that should be considered. Owing to the collection of real-world data and the voluntary nature of participation in the FOS and GOS registries, data may be incomplete, underreported, or subject to selection bias. For example, underreporting of AEs and IRRs may be more likely with patients self-administering ERT infusions and managing their own care compared with infusions being administered and monitored by an HCP in the clinic/hospital or home setting. Moreover, the number of patients included in this analysis is relatively small, particularly with respect to the velaglucerase alfa self-administration population. Lastly, the selection of patients for self-administration, self-administration practices, and patient training may vary between sites and countries. Exploring if any country-specific practices are associated with improved outcomes could help enhance the care of patients who are self-administering ERT infusions. Countries not yet implementing self-administration practices could benefit from guidance on best practices provided by other countries with established self-administration programs.

Conclusions

These findings suggest that self-administration of agalsidase alfa or velaglucerase alfa infusions are not associated with additional safety risks compared with HCP-supported infusions and are a suitable option for qualifying patients. Information relating to self-administration of ERT may help to inform treatment management decisions as part of individualized patient care. Patients self-administering ERT infusions are afforded benefits including independence, flexibility, and control, all of which encourage self-management of their care. Successful self-administration programs are established in several countries and could serve as resources for other countries considering implementing self-administration practices for agalsidase alfa and velaglucerase alfa. Further research is warranted to support these findings and to explore further the long-term safety and efficacy of ERT self-administration.

Availability of data and materials

The datasets, including the redacted study protocol, redacted statistical analysis plan, and individual Participants data supporting the conclusions of this article, will be made available after the publication of study results within three months from initial request to researchers who provide a methodologically sound proposal. The data will be provided after its de-identification, in compliance with applicable privacy laws, data protections and requirements for consent and anonymization.

Abbreviations

AE:

Adverse event

COVID-19:

Coronavirus disease of 2019

ERT:

Enzyme replacement therapy

FOS:

Fabry Outcome Survey

GOS:

Gaucher Outcome Survey

HCP:

Health care provider

ICF:

Informed consent form

ICH E6:

International Conference on Harmonisation Good Clinical Practice guidelines, sixth edition

IRR:

Infusion-related reaction

PY:

Patient-years

SD:

Standard deviation

References

  1. Brady RO, Gal AE, Bradley RM, Martensson E, Warshaw AL, Laster L. Enzymatic defect in Fabry’s disease. Ceramidetrihexosidase deficiency. N Engl J Med. 1967;276(21):1163–7.

    CAS  PubMed  Google Scholar 

  2. Brady RO, Kanfer JN, Bradley RM, Shapiro D. Demonstration of a deficiency of glucocerebroside-cleaving enzyme in Gaucher’s disease. J Clin Invest. 1966;45(7):1112–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Concolino D, Amico L, Cappellini MD, Cassinerio E, Conti M, Donati MA, et al. Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group. Mol Genet Metab Rep. 2017;12:85–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Symptoms Overview 2022 [Available from: https://www.fabrydisease.org/index.php/about-fabry-disease/fabry-disease-symptoms-overview.

  5. Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, et al. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry Registry. Mol Genet Metab. 2008;93(2):112–28.

    CAS  PubMed  Google Scholar 

  6. Eng CM, Fletcher J, Wilcox WR, Waldek S, Scott CR, Sillence DO, et al. Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the fabry registry. J Inherit Metab Dis. 2007;30(2):184–92.

    CAS  PubMed  Google Scholar 

  7. National Fabry Disease Foundation. Fabry disease kidney symptoms 2022 [Available from: https://www.fabrydisease.org/index.php/component/content/article/2-general/129-fabry-disease-kidney-symptoms?Itemid=105.

  8. Arends M, Wanner C, Hughes D, Mehta A, Oder D, Watkinson OT, et al. Characterization of classical and nonclassical Fabry disease: a multicenter study. J Am Soc Nephrol. 2017;28(5):1631–41.

    CAS  PubMed  Google Scholar 

  9. Elstein D, Burrow TA, Charrow J, Giraldo P, Mehta A, Pastores GM, et al. Home infusion of intravenous velaglucerase alfa: experience from pooled clinical studies in 104 patients with type 1 Gaucher disease. Mol Genet Metab. 2017;120(1–2):111–5.

    CAS  PubMed  Google Scholar 

  10. Zimran A, Belmatoug N, Bembi B, Deegan P, Elstein D, Fernandez-Sasso D, et al. Demographics and patient characteristics of 1209 patients with Gaucher disease: descriptive analysis from the Gaucher Outcome Survey (GOS). Am J Hematol. 2018;93(2):205–12.

    PubMed  Google Scholar 

  11. Stirnemann J, Belmatoug N, Camou F, Serratrice C, Froissart R, Caillaud C, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int J Mol Sci. 2017;18(2):441.

    PubMed  PubMed Central  Google Scholar 

  12. National Organization for Rare Disorders (NORD). Gaucher disease 2021 [Available from: https://rarediseases.org/rare-diseases/gaucher-disease/.

  13. Beck M, Ramaswami U, Hernberg-Ståhl E, Hughes DA, Kampmann C, Mehta AB, et al. Twenty years of the Fabry Outcome Survey (FOS): insights, achievements, and lessons learned from a global patient registry. Orphanet J Rare Dis. 2022;17(1):238.

    PubMed  PubMed Central  Google Scholar 

  14. Germain DP, Linhart A. Pegunigalsidase alfa: a novel, pegylated recombinant alpha-galactosidase enzyme for the treatment of Fabry disease. Front Genet. 2024;15:1395287.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Zimran A. How I treat Gaucher disease. Blood. 2011;118(6):1463–71.

    CAS  PubMed  Google Scholar 

  16. Sasa H, Nagao M, Kino K. Safety and effectiveness of enzyme replacement therapy with agalsidase alfa in patients with Fabry disease: post-marketing surveillance in Japan. Mol Genet Metab. 2019;126(4):448–59.

    CAS  PubMed  Google Scholar 

  17. Tsurumi M, Suzuki S, Hokugo J, Ueda K. Long-term safety and efficacy of agalsidase beta in Japanese patients with Fabry disease: aggregate data from two post-authorization safety studies. Expert Opin Drug Saf. 2021;20(5):589–601.

    PubMed  Google Scholar 

  18. Smith L, Rhead W, Charrow J, Shankar SP, Bavdekar A, Longo N, et al. Long-term velaglucerase alfa treatment in children with Gaucher disease type 1 naïve to enzyme replacement therapy or previously treated with imiglucerase. Mol Genet Metab. 2016;117(2):164–71.

    CAS  PubMed  Google Scholar 

  19. Titievsky L, Schuster T, Wang R, Younus M, Palladino A, Quazi K, et al. Safety and effectiveness of taliglucerase alfa in patients with Gaucher disease: an interim analysis of real-world data from a multinational drug registry (TALIAS). Orphanet J Rare Dis. 2022;17(1):145.

    PubMed  PubMed Central  Google Scholar 

  20. U.S. Food & Drug Administration. Highlights of prescribing information for VPRIV. 2010.

  21. Takeda Canada Inc. Replagal product monograph. 2021.

  22. Marshall J, Ashe KM, Bangari D, McEachern K, Chuang WL, Pacheco J, et al. Substrate reduction augments the efficacy of enzyme therapy in a mouse model of Fabry disease. PLoS ONE. 2010;5(11):e15033.

    PubMed  PubMed Central  Google Scholar 

  23. Kisinovsky I, Cáceres G, Coronel C, Reisin R. Home infusion program for Fabry disease: experience with agalsidase alfa in Argentina. Medicina (B Aires). 2013;73(1):31–4.

    PubMed  Google Scholar 

  24. Linthorst GE, Vedder AC, Ormel EE, Aerts JM, Hollak CE. Home treatment for Fabry disease: practice guidelines based on 3 years experience in The Netherlands. Nephrol Dial Transpl. 2006;21(2):355–60.

    CAS  Google Scholar 

  25. Elstein D, Abrahamov A, Oz A, Arbel N, Baris H, Zimran A. 13,845 home therapy infusions with velaglucerase alfa exemplify safety of velaglucerase alfa and increased compliance to every-other-week intravenous enzyme replacement therapy for Gaucher disease. Blood Cells Mol Dis. 2015;55(4):415–8.

    CAS  PubMed  Google Scholar 

  26. Smid BE, Hoogendijk SL, Wijburg FA, Hollak CE, Linthorst GE. A revised home treatment algorithm for Fabry disease: influence of antibody formation. Mol Genet Metab. 2013;108(2):132–7.

    CAS  PubMed  Google Scholar 

  27. Beck M, Gaedeke J, Martus P, Karabul N, Rolfs A. [Home-based infusion therapy–a feasible approach for chronically ill patients? A new path to provide superior patient care exemplified for Fabry’s disease] [Article in German]. Dtsch Med Wochenschr. 2013;138(46):2345–50.

    CAS  PubMed  Google Scholar 

  28. Hughes DA, Mlilligan A, Mehta A. Home therapy for lysosomal storage disorders. Br J Nurs. 2007;16(22):1384–9.

    PubMed  Google Scholar 

  29. Milligan A, Hughes D, Goodwin S, Richfield L, Mehta A. Intravenous enzyme replacement therapy: better in home or hospital? Br J Nurs. 2006;15(6):330–3.

    CAS  PubMed  Google Scholar 

  30. Mengel E, Stulnig TM, Kralewski M, Lachmann A, Martus P. Home infusion therapy with velaglucerase alfa for Gaucher disease type 1 in Germany and Austria. Mol Genet Metab. 2020;129(2):S109. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ymgme.2019.11.281.

    Google Scholar 

  31. Lachmann A, Kurschat C, Fritsch A, Lagler F, Sunder-Plassmann G, Martus P, Kralewski M, Hennermann JB. Home infusion therapy with agalsidase alfa for patients with Fabry disease in Germany and Austria. Mol Genet Metab. 2020;129(2):S94. https://doiorg.publicaciones.saludcastillayleon.es/10.1016/j.ymgme.2019.11.236.

    Google Scholar 

  32. Kusztal M, Kłopotowski M, Bazan-Socha S, Błażejewska-Hyżorek B, Pawlaczyk K, Oko A, et al. Is home-based therapy in Fabry disease the answer to compelling patients’ needs during the COVID-19 pandemic? Survey results from the Polish FD Collaborative Group. Adv Clin Exp Med. 2021;30(4):449–54.

    PubMed  Google Scholar 

  33. Elstein D, Giugliani R, Muenzer J, Schenk J, Schwartz IVD, Anagnostopoulou C. Impact of the COVID-19 pandemic on the standard of care for patients with lysosomal storage diseases: A survey of healthcare professionals in the Fabry, Gaucher, and Hunter Outcome Survey registries. Mol Genet Metab Rep. 2021;28:100788.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Rasutis VM, Katzberg HD, Bril V. High-dose subcutaneous immunoglobulin in patients with multifocal motor neuropathy: a nursing perspective. J Infus Nurs. 2017;40(5):305–12.

    PubMed  Google Scholar 

  35. Longhurst HJ, Carr S, Khair K. C1-inhibitor concentrate home therapy for hereditary angioedema: a viable, effective treatment option. Clin Exp Immunol. 2007;147(1):11–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Petraroli A, Squeglia V, Di Paola N, Barbarino A, Bova M, Spanò R, et al. Home therapy with plasma-derived C1 inhibitor: a strategy to improve clinical outcomes and costs in hereditary angioedema. Int Arch Allergy Immunol. 2015;166(4):259–66.

    CAS  PubMed  Google Scholar 

  37. Khair K, Meerabeau L, Gibson F. Self-management and skills acquisition in boys with haemophilia. Health Expect. 2015;18(5):1105–13.

    PubMed  Google Scholar 

  38. Hughes DA, Deegan P, Giraldo P, Goker-Alpan O, Lau H, Lukina E, et al. Switching between enzyme replacement therapies and substrate reduction therapies in patients with Gaucher disease: data from the Gaucher Outcome Survey (GOS). J Clin Med. 2022;11(17):5158.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Sechi A, Macor D, Valent S, Da Riol RM, Zanatta M, Spinelli A, et al. Impact of COVID-19 related healthcare crisis on treatments for patients with lysosomal storage disorders, the first Italian experience. Mol Genet Metab. 2020;130(3):170–1.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fraser N, Georgiou R, Brown M, Bischoff C, Agnew R. The Australian ATHOMETM Infusion service experience. Society for the study of inborn errors of metabolism (SSIEM) 2014 Annual Symposium; Innsbruck, Austria: J Inherit Metab Dis; September 2–5, 2014.

  41. Ltd TPAP. Australian product information, Replagal® (agalsidase alfa ghu) 2020 [12]. Available from: https://www.health.gov.au/resources/collections/life-saving-drugs-program-resources-fabry-disease.

  42. Ltd TPAP. Australian product information - VPRIV®(velaglucerase alfa ghu) powder. 2020.

  43. Government of Brazil. Ministry of Health [Ministério da Saúde] [in Portuguese]: gov.br; 2023 [Available from: https://www.gov.br/saude/pt-br.

  44. FOS steering committee. Fabry ourcome survey annual report 2016. Shire; August 2017.

  45. V Dobé Pandemie Onemocnění COVID-19 Jsou Pacienti se VzácnÝmi Onemocněními Vysoce Rizikovou Skupinou [press release]. České asociace pro vzácná onemocnění. April 4, 2020.

  46. European Medicines Agency. Replagal, Annex I, Summary of product characteristics. Takeda Pharmaceuticals International AG Ireland Branch; 2006.

  47. Zimran A, Hollak CE, Abrahamov A, van Oers MH, Kelly M, Beutler E. Home treatment with intravenous enzyme replacement therapy for Gaucher disease: an international collaborative study of 33 patients. Blood. 1993;82(4):1107–9.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank the patients enrolled in FOS and GOS, their caregivers, the physicians, and their staff, and extend their gratitude to Tanya Collin-Histed, CEO International Gaucher Alliance, for her valued discussions regarding home infusion. Under the direction of the authors, Megan Schladetsch, Ph.D., employee of Excel Scientific Solutions, Inc., a member of the Envision Pharma Group, provided writing assistance for this manuscript. Editorial assistance in formatting, proofreading, and copy editing was also provided by Excel Scientific Solutions, Inc.

Funding

The FOS and GOS registries are funded by Takeda Pharmaceuticals International AG, Glattpark-Opfikon, Switzerland. Takeda Development Center Americas, Inc., Lexington, MA, USA, provided funding to Excel Scientific Solutions, Inc. for support in writing and editing this manuscript.

Author information

Authors and Affiliations

  1. Gaucher Unit and Pediatric Hematology/Oncology Unit, The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel

    Shoshana Revel-Vilk

  2. Faculty of Medicine, Hebrew University, Jerusalem, Israel

    Shoshana Revel-Vilk

  3. Lysosomal Storage Disorders Unit, Royal Free London NHS Foundation Trust and University College London, London, UK

    Uma Ramaswami

  4. Vall d’Hebron Institute of Research (VHIR), Vall d’Hebron Barcelona Hospital Campus, MPS-Spain Medical Committee, Barcelona, Spain

    Guillem Pintos-Morell

  5. Lysosomal Disorders Unit, Royal Free London NHS Foundation Trust, University College London, London, UK

    Derralynn Hughes

  6. The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, Australia

    Kathy Nicholls

  7. Hospital Británico de Buenos Aires, Buenos Aires, Argentina

    Ricardo Reisin

  8. Department of Genetics, UFRGS, Porto Alegre, Brazil

    Roberto Giugliani

  9. Dasa Genomics, Sao Paulo, Brazil

    Roberto Giugliani

  10. Casa dos Raros, Porto Alegre, Brazil

    Roberto Giugliani

  11. INAGEMP, UFRGS, Porto Alegre, Brazil

    Roberto Giugliani

  12. Medical Genetics Service, HCPA, Porto Alegre, Brazil

    Roberto Giugliani

  13. Lysosomal and Rare Disorders Research and Treatment Center, Fairfax, VA, USA

    Ozlem Goker-Alpan

  14. Gaucher Unit The Eisenberg R&D Authority, Shaare Zedek Medical Center, Jerusalem, Israel

    Majdolen Istaiti

  15. Takeda Development Center Americas (at time of study start), Lexington, MA, USA

    Aidan Gill

  16. Regional Center for Rare Diseases, University Hospital of Udine, Udine, Italy

    Maurizio Scarpa

  17. Takeda Pharmaceuticals International AG, Zurich, Switzerland

    Jaco Botha

Authors
  1. Shoshana Revel-Vilk
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  2. Uma Ramaswami
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  3. Guillem Pintos-Morell
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  4. Derralynn Hughes
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  5. Kathy Nicholls
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  6. Ricardo Reisin
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  7. Roberto Giugliani
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  8. Ozlem Goker-Alpan
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  9. Majdolen Istaiti
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  12. Jaco Botha
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Contributions

SRV, UR, GPM, DH, KN, RR, RG, OGA, MI, and MS recruited patients, collected data, and provided a critical review of data analysis. AG contributed to study conception. JB performed data analysis. All authors reviewed and edited the manuscript. All authors read and approved the final manuscript and support the decision to submit the manuscript for publication.

Corresponding author

Correspondence to Jaco Botha.

Ethics declarations

Ethics approval and consent to participate

FOS and GOS registries have been approved by the ethics institutional review boards of participating centers and are conducted in compliance with relevant global and local regulations and best practices, Good Pharmacoepidemiological Practice, Good Research for Comparative Effectiveness principles, and the relevant principles of the International Conference on Harmonisation Good Clinical Practice guidelines (ICH E6), as appropriate for an observational registry. All participants provided written informed consent.

Consent for publication

Not applicable.

Competing interests

SRV received grant/research support, honoraria, and advisory fees from Pfizer, Sanofi/Genzyme and Takeda. UR received honoraria for lectures and advisory boards from Amicus, Sanofi and Takeda; research grants from Amicus, Intrabio and Takeda. GPM received honoraria as a speaker and/or consultancy from Amicus, Chiesi, Lucane, and Takeda and unrestricted grants for research of Rare Diseases at VHIR from Sanofi and Takeda. DH received honoraria for speaking and advisory boards from Amicus, Chiesi, Freeline, Idorsia, Sangamo, Sanofi and Takeda. KN reports honoraria from Amicus Therapeutics, Sanofi Genzyme, and Takeda; and is a member of the FOS Steering Committee. RR reports honoraria, speaker fees, and consulting fees from Amicus Therapeutics, CSL Behring, Gador, Sanofi Genzyme, Novartis, and Takeda; and is a member of the FOS Steering Committee. RG received research grants, investigator fees, speaker/consultancy honoraria, and travel support to attend scientific meetings from Allievex, Amicus, Avrobio, Asafaros, BioMarin, Chiesi, Cyclo, DASA, Idorsia, Inventiva, Janssen, JCR, Lysogene, Novartis, Paradigm, PassageBio, Pfizer, Protalix, PTC, RegenxBio, Sanofi, Sigilon, Sobi,Takeda and Ultragenyx. OGA has received grant support from 4DMT, Chiesi, Idorsia, Protalix, Sangamo, and Sanofi for clinical research trials and from Sanofi and Takeda for other investigator-initiated studies; consulting fees from Chiesi, Sanofi, Takeda, and Uniqure; honoraria for speaker bureaus from Sanofi and Takeda and participates on the Advisory Board on Fabry Disease for Chiese and Sanofi. MI received support for the SZMC Gaucher Unit from Sanofi/Genzyme for participation in the ICGG Registry, from Takeda for the GOS Registry, and Pfizer for TALIAS; the Unit also receives research grants from Centogene, Pfizer, Sanofi/Genzyme and Takeda. AG was an employee of Takeda and stockholder in Takeda at the time of study start. MS has received honoraria and travel support from Alexion, Bi-938 oMarin, CHIESI, Orchard, Regenexbio, Sanofi, Takeda, and Ultragenyx. JB is an employee of Takeda and holds stock options in Takeda.

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Revel-Vilk, S., Ramaswami, U., Pintos-Morell, G. et al. Safety analysis of self-administered enzyme replacement therapy using data from the Fabry Outcome and Gaucher Outcome Surveys. Orphanet J Rare Dis 20, 145 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13023-024-03416-2

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Orphanet Journal of Rare Diseases

ISSN: 1750-1172