Table 2.
PROMs/ObsROMs HrQoL instruments used across IMDs to evaluate therapeutic benefit in clinical studies
| IMD | Sample (age in years) | Treatment/Therapy | Follow up time | HrQoL tool | Effects on HrQoL and major findings | Ref. |
|---|---|---|---|---|---|---|
| Carnitine palmitoyl transferase II deficiency | Adults | Bezafibrate | 6 months | SF-36 | - ↑ HrQoL in all domains, specially role limitations due to physical health and body pain | [158] |
| Children and adults (10–55) | Anaplerotic diet therapy | 7–61 months | SF-36 | - ↑ HrQoL in the physical component score | [106] | |
| Fabry disease | Male adults (16–48) | Agalsidase-β | 10 days-20 weeks | SF-36 | - Phase 1/2 trial that proved the efficiency and safety of Fabrazyme including an ↑ HrQoL, namely regarding bodily pain, general health, vitality, physical role and emotional role domains. Placebo effects were noticed. | [107, 108] |
| Adults and adolescents (> 14) | Agalsidase-β | 3 years | SF-36 | - ↑ HrQoL more pronounced in men | [109] | |
| Adults (41.4, mean) | Agalsidase-β | 2 years | SF-36 | - Ns changes in HrQoL | [141] | |
| Male adults (16–34) | Agalsidase-β | 20 weeks | SF-36 | - ↑ HrQoL with significant changes in the general health and the mental component score | [110] | |
| Adults | Agalsidade-α | 2 years | EQ-5D | - Significant ↑ HrQoL | [120] | |
| Adults | Agalsidase-α | 2 years | EQ-5D | - Significant ↑ HrQoL which negatively correlates with pain | [122] | |
| Adults (39.2 ± 12.3, mean) | Agalsidase-α | 5 years | EuroQoL | - Significant ↑ HrQoL | [121] | |
| Adults (males: 44.25 ± 11; females: 52.3 ± 10.5, means) | Agalsidase-α | 4 weeks | EQ-5D | - Ns differences in HrQoL in the 3 dose regimens. (NCT01218659) | [129] | |
| Heterozygous females (20–66) | Agalsidase-α | 55 weeks | SF-36 | - Phase 3 study that proved the agalsidase-α safety and efficacy in heterozygous females with significant ↑ HrQoL, mostly in the physical domain. | [111] | |
| Children (7–18) | Agalsidase-α | 55 weeks | HUI, CHQ | - Phase 2 study that showed the efficiency and safety of agalsidase-α, however HrQoL remained unchanged. (NCT01363492) | [40] | |
| Adults (42.5 ± 12.5, mean) | ERT | 6.1 ± 2.5 years | EQ-5D | - ↑ HrQoL in severely affected males - Unchanged HrQoL in women - Annual ↓ in HrQol in non-classical patients |
[74] | |
| Adults (26–68) | ERT | 4–7 years | SF-36 | - Stable HrQoL except for the social functioning score. | [161] | |
| Children (6–18) | ERT | – | PedsQL | - Children on ERT had higher scores that approached significance. | [83] | |
| Adults (16–74) | Migalastat | 2 years | SF-36 | - Results did not reveal any clinical benefit (NCT00925301 and NCT01458119) | [162] | |
| Familial hypercholesterolemia | Children and adults (9–57) | LDL apheresis | NA | SF-36 | - ↑ HrQoL in 2 patients with baseline data | [112] |
| Gaucher disease type I | Children and adults (12–70) | Imiglucerase | 4 years | SF-36 | - Significant ↑ HrQoL in the physical component score and, particularly, the physical functioning, physical role limitations and bodily pain subscores. (NCT00365131) | [60] |
| Adults (18–82) | Imiglucerase | 2 years | SF-36 | - Since baseline HrQoL approached those of the general population, there was no space for improvements and ns changes were observed. | [164] | |
| Adults (17–69) | Miglustat | 6–24 months | SF-36 | - Miglustat administration significantly ↑ HrQoL, while imiglucerase or combination of both reduced HrQoL | [113] | |
| Adults (35.2 ± 10.2, mean at start) | Miglustat | 12–48 months | SF-36 | - Similar improvements in HrQoL between miglustat and ERT-treated patients. | [114] | |
| Adults (18–66) | ERT | 2 years | SF-36 | - Self-perception of global health, physical activity and social functioning improved with ERT. | [61] | |
| Children and adults (> 5) | ERT or SRT | 10 years (mean) | SF-36 | - 65 patients achieved the therapeutic goal for HrQoL but differences between treated and untreated patients were ns. | [99] | |
| Children and adults (> 12) (one type 3 Gaucher disease patient) | ERT | 8.5 years (mean) | SF-36 | - Bodily pain was significantly decreased in ERT-naïve patients but physical functioning, role physical, general health, social functioning and role emotional scores showed clinical meaningful impairments too. - Gaucher disease patients receiving ERT have significant higher scores than Fabry disease patients also receiving ERT. |
[128] | |
| Hereditary hemochromatosis | Adults (55 ± 9.0, mean) | Erythrocytaphe-resis | 2 years | SF-36 | - There is no benefit in terms of HrQoL of erythrocytapheresis over phlebotomy. (NCT01398644) | [155] |
| MPS IH | Children and adults (2–25) | Hematopoietic cell transplant | 9 years (mean) | CHQ-PF50 | - Higher age at transplant correlates with poor physical scores | [36] |
| LC-FAOD | Children and adults (12.06 ± 13.2, mean) | Triheptanoin (UX007) | 24 weeks | SF-12, SF-10 | - Significant ↑ HrQoL in the physical and mental domains for adults but not for children. (NCT01886378) | [38] |
| MPS VI | Children and adults (5–21) | Arylsulfatase B | 1.3–5-4 years | TAPQOL, TACQOL | - ↑ HrQoL regarding lung problems, sleeping, liveliness, positive mood, social functioning and communication - ↓ HRQoL in the anxiety and negative emotions domains |
[49] |
| McArdle’s disease | Adults (18–60) | Ramipril | 3 months | SF-36 | -↑ HrQoL in the emotional status and social role in both ramipril and placebo groups | [100, 101] |
| MPS IV | Children and adults (9.8–42.2) | Elosulfase-α | 48–96 weeks | SF-36, PODCI | - Stable HrQoL, except in 1 child with ↓ HrQoL (NCT01697319) | [115] |
| Nephropathic cystinosis | Children and adolescents (6–21) | Delayed-release cysteamine birtrate | 2 years | PedsQL | - Significant ↑ HrQoL particularly in social, school and total function. | [123] |
| Pompe disease | Adults (41–42) | Alglucosidase-α | 2 years | SF-36 | - ↑ HrQoL, particularly in the bodily pain domain | [102] |
| Adults (28–62) | Alglucosidase-α | 52 weeks | SF-36 | - 3/5 patients improved both physical and mental scores while 1/5 improved only the mental or the physical score | [103] | |
| Late onset adults (27–73) | Alglucosidase-α | 36 months | SF-36 | - Ns differences from baseline | [117] | |
| Late onset adults (21–69) | Alglucosidase-α | 1 year | SF-36 | - Ns differences from baseline | [118] | |
| Adults (24–76, at start) | ERT | 4 years (median) | SF-36 | - Significant ↑ HrQoL in the physical functioning, role physical, general health, vitality and mental health subscores, after 2 years. After 4 years, the bodily pain domain significantly worsened. | [64] | |
| Adult (65) | L-alanine | 6 months | SF-36 | - ↓ HrQoL, mainly the physical domain due to worsening of muscle function. ↑ HrQoL during placebo interval reflecting the optimism of entering a trial. | [104] | |
| Adults (20–71) | Exercise program | 12 weeks | SF-36 | - Borderline ↑ HrQoL at the mental component | [105] | |
| Late onset adults (35.5–60.7) | Inspiratory muscle training program | 8 weeks | NHP | - Significant ↑ HrQoL exclusively in the social isolation subscore | [119] | |
| PKU | Children and adults (4–44) | BH4 | 1 year | PedsQL, TAAQOL | - Unchanged HrQoL and similar between responsive and non-responsive patients | [46] |
| Children and adolescents (6.6–18.7) | BH4 | 6 months | KINDL | - Unchanged HrQoL and similar between responsive and non-responsive patients | [44] | |
| Children and adults (10–49) | BH4 | 1 year | PKU-QOLQ | - ↑ HrQoL in responders, provisional responders and non-responders in terms of impact, satisfaction | [124] | |
| Wilson disease | Children and adults (8–41) | Orthotopic liver transplantation | 97 months (mean) | SF-36 | - Ns difference between norm-based scores and patients who underwent transplantation | [116] |
| Adults (36.6 ± 12.9) | D-penicillamine, trientine, zinc | 8.1–12.6 years (mean) | SF-36 | - D-penicillamine-treated patients had the highest HrQoL scores compared to trientine- or zinc-treated patients. | [140] |
Abbreviations: AQOL-4D Assessment of Quality of Life 4D, CHQ Child Health Questionnaire, HUI Health Utilities Index, LDL Low-density lipoprotein, NA non available, NHP Nottingham Health Profile, Ns No significant, PedsQL Pediatric Quality of Life Inventory, PGWBI Psychological General Well-Being Index, PLC Profile for the Chronically Ill, PODCI Pediatric Outcomes Data Collection Instrument, PKU-QOL Phenylketonuria-Quality of Life, SF-36 36-Item Short Form Survey, TAAQOL TNO-AZL questionnaire for Adult’s HrQoL, TACQOL TNO-AZL Questionnaire for Children’s HrQoL, TAPQOL TNOAZL Questionnaire for Preschool Children’s HrQoL, VSP-A Vécu et Santé Percue de l’Adolescent, WHOQOL World Health Organization Quality of Life