A total of 280 participants with FD completed the survey (Table 1). Respondents ranged in age from 18 to 77 years, with a mean age of 47 years. The majority of participants were female (68%, 191/280; male: 31%, 88/280; non-conforming: 1%, 1/280). Most respondents reported they were currently receiving FD treatment (84%, 234/280; male: 95%, 84/88; female: 78%, 149/191); the remainder were not currently receiving any treatment (13%, 37/280; male: 1%, 1/88; female: 19%, 36/191), or they selected “other” (3%, 9/280; male: 3%, 3/88; female: 3%, 6/191) for treatment status. Of those currently receiving treatment for FD, 89% (208/234) were receiving ERT with agalsidase beta (91%, 189/208) or agalsidase alfa (9%, 19/208), and 11% (26/234) were receiving chaperone therapy with migalastat. Respondents not currently receiving any treatment were either treatment naïve (10%, 28/280) or had previously been on ERT but had discontinued (3%, 9/280). Examples of free text responses for “other” included “infusion,” “PRX-102” (pegunigalsidase alfa), and “preparing to begin treatment.”

Respondents were highly educated, with most (56%, 158/280) reporting that they had completed college (38%, 106/280) or a master’s degree or above (19%, 52/280). More than half (54%, 152/280; male: 65%, 57/88; female: 50%, 95/191) of respondents were employed full-time or part-time. Nearly one-third (29%, 82/280) reported being retired; of those, 61% (50/82) indicated that this was due to disability and their average age was 54 years (25–70). All respondents who reported themselves to be stay-at-home household managers were female (n = 14). Most respondents had health insurance, with more than half (56%, 157/280) reporting they had commercial or private insurance and more than one-third (36%, 100/280) reporting they had government insurance from Medicare or Medicaid. A total of 4 respondents of 280 (1%) reported having no insurance and were all ≤ 64 years; 3% (3/88) of males and less than 1% (1/191) of females were not insured.

Approximately half of respondents were diagnosed with FD more than 10 years ago (51%, 144/280). Nearly two-thirds (65%, 181/280; males: 70%, 62/88; females: 62%, 118/191) reported that they had been diagnosed with classic FD. Notably, respondents with classic FD comprised 68% (159/234) of those currently receiving treatment.

Respondents most often reported that their FD was primarily managed by a geneticist (46%, 128/280). Other managing physicians included a nephrologist (23%, 63/280), a primary care or family physician (16%, 45/280), a cardiologist (7%, 20/280), and a neurologist (3%, 8/280). Six respondents (2%, 6/280) reported that they did not have a physician managing their FD. All respondents currently (n = 208) or previously receiving ERT (n = 9) reported having their disease managed by a physician, whereas nearly one-fifth (18%, 5/28) of treatment-naïve respondents did not have a physician managing their disease. Respondents who were currently receiving agalsidase beta (48%, 90/189) or chaperone therapy (58%, 15/26), as well as those who were treatment naïve (46%, 13/28) were most often managed by a geneticist, whereas those currently receiving agalsidase alfa were most often managed by a nephrologist, a primary care or family physician, or a cardiologist (each 26%, 5/19).

The questionnaire delineated the proportion of respondents who experienced various symptoms of FD, and these are reported in Table 2. The most common symptoms overall were low energy or fatigue (72%, 201/280), tingling (62%, 174/280) or pain in the hands and/or feet (60%, 168/280), ringing in ears and/or hearing loss (54%, 151/280), general body pains and/or pain crises (51%, 143/280), and abdominal and/or stomach pain (50%, 140/280). Of the common symptoms, 73% (90/124) of those aged 18–44 years reported tingling in extremities, whereas low energy/fatigue was most commonly reported by those aged above 45 years (78%, 122/156); there were no clear differences when stratified by gender. When asked to characterize the severity of their FD symptoms, nearly half reported symptoms were mild-to-moderate (49%, 136/280), and the remainder reported they were bothersome (38%, 106/280) or difficult to control (14%, 38/280). Compared to the overall population, symptom severity was similar for those currently receiving treatment (Fig. 2). A larger percentage of treatment-naïve respondents (75%, 21/28) reported mild-to-moderate symptoms compared with those currently receiving treatment (45%, 106/234). When considering gender, males equally reported having bothersome or mild-moderate symptoms (41% each, 36/88), while more females reported their symptoms as mild-moderate (52%, 99/191) than bothersome (37%, 70/191).

Fabry disease symptom severity. ERT, enzyme replacement therapy; FD, Fabry disease

Respondents were asked to indicate how often their kidney or heart function was monitored by laboratory tests or examinations (Fig. 3). Overall, 48% (133/280) had their kidney function monitored at least every 6 months, and 88% (246/280) had their kidney function monitored at least every 12 months. Similarly, 40% (112/280) had their heart function monitored at least every 6 months, and 82% (230/280) had their heart function monitored at least every 12 months. When stratified by treatment status, a higher proportion of those currently receiving treatment were monitored at every time point compared with those who had previously received ERT but had discontinued it or those who were treatment naïve. In consideration of gender, there were more males (35%, 31/88) receiving laboratory testing for assessment of kidney function every 3 months than females (13%, 24/191); females were more likely to be assessed once a year (41%; 79/191 vs. 27%, 24/88). A similar trend was observed for heart function evaluations.

Monitoring frequency for kidney and heart function. (A) Kidney function. (B) Heart function. ERT, enzyme replacement therapy; FD, Fabry disease

More than half of all respondents reported stable disease without major kidney or heart damage (53%, 147/280). Among those currently receiving treatment, nearly half (48%, 112/234) reported stable disease; the remainder reported that their kidney or heart function was already affected (38%, 90/234) or that they had worsening kidney or heart function damage (14%, 32/234). Among those not currently receiving treatment, most reported stable disease (78%, 29/37). When stratified by gender, females were more likely to report stable disease (58%, 110/191) than males (41%, 36/88); males (24%, 21/88) were more likely to report worsening kidney or heart function damage than females (7%, 13/191). Over 60% (80/124) of patients aged 18–44 years reported stable disease, compared with 48% (57/118) and 26% (10/38) of patients aged 45–64 and over 65 years, respectively.

Most respondents (82%, 230/280) were satisfied with how their disease progression was being monitored, with 36% (102/280) reporting that their disease was monitored “well” and 23% each reporting that it was monitored “moderately well” (65/280) or “excellent” (63/280). A larger percentage of respondents currently receiving treatment expressed a positive perception of monitoring of disease progression compared with those who had previously been treated or who were treatment naïve. Although most respondents were satisfied with their disease monitoring, most (82%, 230/280) also perceived their disease as worsening even when laboratory tests and clinical assessments appeared stable.

Three-quarters of respondents (75%, 211/280) reported currently receiving ERT at the time of completing the questionnaire, and the remainder had been on ERT but discontinued (10%, 29/280) or had never tried ERT (14%, 40/280). Women comprised a greater proportion of those who had never tried ERT (90%, 36/40) or had tried ERT but discontinued (79%, 23/29) than those who were currently receiving ERT (63%, 132/211). Among respondents who reported currently receiving ERT, 30% (64/211) started treatment more than 10 years prior, 22% (46/211) started 6 to 10 years prior, and 27% (56/211) started 3 to 5 years prior. Among those who reported that they had previously been on ERT but had discontinued, the most common probed reason for discontinuation was switching to oral treatment (52%, 15/29); other probed reasons included lengthy infusions, IRRs, and insurance issues (each 14%, 4/29); additionally, four spontaneously reported COVID-19 as another reason for discontinuation. Respondents were able to choose multiple reasons if more than one applied.

About half of respondents reported that their ERT infusions were administered at home. Infusion duration ranged from 30 min to 8 h (Fig. 4). Approximately 40% (85/211) of respondents currently receiving ERT reported an infusion duration of 3 or more hours; interestingly, more respondents (72%, 21/29) who had previously received ERT, but not currently on ERT, reported a duration of 3 or more hours. Taking medication to manage or prevent IRRs (termed premedication) was reported by 53% (112/211) of respondents who were currently receiving ERT and 66% (19/29) of those who had previously received ERT. Among those who reported taking premedication, 43% (48/112) who were currently receiving ERT and 37% (7/19) who previously received ERT indicated this posed a moderate or significant inconvenience. Among all respondents who currently or previously received ERT, only 36% (87/240) reported they had been tested for ADAs; of those, 30% (26/87) reported they tested positive, 39% (34/87) reported they tested negative, and 31% (27/87) were not able to recall their results. When stratified by gender, 48% (40/84) of males reported having received antibody testing compared with 30% (47/155) of females. Additionally, more females reported not being aware of such a test (16%, 25/155) compared with males (7%, 6/84).

Burden of ERT: Infusion duration reported by respondents currently or previously receiving ERT (N = 240). ERT, enzyme replacement therapy

About half of the respondents currently receiving ERT (51%, 108/211) or previously receiving ERT (48%, 14/29) reported temporary symptom worsening between infusions. Among patients who reported symptom worsening between infusions, the most common symptoms reported between infusions were low energy or fatigue (75%, 92/122), pain in hands or feet (52%, 64/122), general body pains or pain crises (39%, 48/122), tingling in hands or feet (38%, 46/122), and abdominal or stomach pain (34%, 42/122) (Fig. 5). Except for low energy or fatigue (male: 59%, 23/39; female: 83%, 68/82), there were no clear differences in symptom worsening when stratified by gender. Respondents most often reported symptom worsening 1 to 2 days (34%, 41/122) or 3 to 4 days (35%, 43/122) before their next infusion was due, and 17% (21/122) reported that symptom worsening could occur at any time between infusions. Only about half (48%, 59/122) reported their symptom worsening to their physician, and of those who reported it, only 41% (24/59) reported that their physician prescribed medication to manage their symptoms or changed their treatment regimen. Among those who previously received ERT and reported their symptom worsening to their physician, all but one reported that their physician did not prescribe medication for symptom management or make any changes to their treatment regimen. Respondents who reported symptom worsening between infusions (n = 122) were asked to rate the impact of symptom worsening on QoL on a 5-point scale, wherein 1 denoted no impact, and 5 denoted significant interference with daily activities. The overall median score was 3 (range, 1–5); the median score was identical for males and females (range, males: 2–5; females: 1–5), indicating that symptom worsening had a moderate impact on daily activities (score of 3, n = 48; score of 4, n = 26; score of 5, n = 8).

Symptoms reported by respondents who experienced symptom worsening between ERT infusions (N = 122). ERT, enzyme replacement therapy