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Table 2 PROMs/ObsROMs HrQoL instruments used across IMDs to evaluate therapeutic benefit in clinical studies

From: Patient and observer reported outcome measures to evaluate health-related quality of life in inherited metabolic diseases: a scoping review

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]

  1. 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