Table 2.
Summary of results by outcome parameters in clinical trials and post-marketing studies of enzyme replacement therapy (ERT) in MPSs. The main findings of outcome parameters are reported summarizing data of all types of MPSs together.
| Outcome Parameters | Characteristics of the Study | Type MPS | Age (Years) | Number of Patients | Main Findings | References |
|---|---|---|---|---|---|---|
| uGAGs | Phase II/III Clinical Trials | I, II, IV, VI, VII | 5–57 | 440 | Significant reduction after 6 months | [17,18,19,21,22,30,31,32,33] |
| Extension studies/observational | I, II, VI | 0.17–58 | 558 | Persistent reduction after years | [29,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52] | |
| OXIDATIVE STRESS, PRO-INFLAMMATORY BIOMARKERS | Research studies in human subjects on ERT | I, II, IV | 1–36 | 60 | Partial improvement or no effect on lipid peroxidation, protein oxidative damage, DNA damage and increased pro-inflammatory cytokines | [53,54,55,56,57,58] |
| ORGANOMEGALY | Phase II/III clinical trials | I, II, VI | 5–45 | 264 | decreased | [17,18,19,21,30,31,32,33] |
| Extension studies/observational | I, II, VI | 0.17–58 | 384 | Decreased-normalized | [36,38,40,41,43,45,46,48,49,51,59] | |
| Observational | II, VI | 1.25–29.5 | 49 | Only some decreased, the others unchanged | [42,50,60] | |
| OSAs/AHI | Phase II/III trials | I, II | 6–43 | 47 | Decreased AHI | [17,32] |
| Extension studies/observational | I, II | 0.5–43 | 82 | Decreased AHI | [36,45,46,59,61] | |
| ADENO-TONSILS HYPERTROPHY | Extension studies/observational | I, II, IIIA, IVA, VI, | 1–27 | 96 | No improvement | [40,49,50,62,63,64] |
| TRACHEOBRONCHOMALACIA/MEDIASTINAL STORAGE | Observational | II, IVA, VI | 12–50 | 8 | No improvement | [65,66,67,68] |
| SPIROMETRY TESTS (FEV1, FVC, FEV1%, MVV) | Phase II/III | I, II, IVA | 5–57 | 339 | improvement | [17,19,22,31,32] |
| Phase II/III | VI | 5–29 | 39 | No improvement | [18] | |
| Extension/observational | I, II, IVA, VI | 2–58 | 715 | Stabilization or improvement | [36,37,38,41,43,49,69,70,71,72] | |
| Observational | IVA, VI | 1.25–43 | 17 | Stabilization or gradual decline | [60,73] | |
| HEART HYPERTROPHY | Extension/observational | I, II, IVA, VI | 0.5–53.9 | 177 | Improvement or stabilization | [40,41,42,46,51,74,75,76,77,78] |
| Extension/observational | II, VI | 1.5–37 | 70 | Stabilization or worsening | [34,37,47] | |
| HEART VALVES | Extension/observational | I, II, IVA, VI | 0.5–53.9 | 336 | Stabilization or worsening | [34,36,37,40,41,44,46,47,51,59,74,75,76,77,78,79] |
| VESSELS | Observational | I, II, IVA, VI | 3.4–27.8 | 54 | No apparent efficacy on vessels abnormalities | [80,81,82,83,84] |
| HEARING | observational | VI | 0.17–58 | 31 | Stabilized or improved | [42,47,49] |
| Observational | I, II, IVA, VI | 1.25–29.5 | 174 | Stabilized or worsened | [45,60,85,86] | |
| EYES- CORNEAL CLOUDING | observational | I | 5–22 | 8 | No apparent efficacy | [59] |
| Observational | I, IVA, VI | 4–44 | 38 | Stabilization or worsening | [87,88,89,90] | |
| JOINT RESTRICTION (MEASURED WITH PASSIVE ROM) | Phase II/III trials | I, II, VI | 5–43 | 154 | Mild improvement | [17,19,30,31,33] |
| Phase II/III trials | VI, VII | 5–35 | 64 | No improvement | [18,21] | |
| observational | I, II, VI | 0.2–53.9 | 257 | Stabilized or improved | [34,36,38,40,41,42,49,51,59,91,92,93] | |
| observational | I, VI | 8–31 | 12 | No improvement | [94,95] | |
| ENDURANCE (6MWT, 12MWT, 3MSC) | Phase II/III trials | I, II, IVA, VI, VII | 5–57 | 437 | Improvement | [17,18,19,21,22,30,31,33] |
| observational | I, II, IVA, VI | 0.7–58 | 577 | Improvement maintained after 3 or more years | [36,37,38,39,40,41,42,43,51,52,70,96,97] | |
| HEALTH RELATED QUALITY OF LIFE QUESTIONNAIRES (MAINLY MPS-HAQ, CHAQ/HAQ) | Phase II/III trials | IVA | 5–57.4 | 176 | Mild improvement | [98] |
| observational | I, II, IVA, VI | 2.3–57.4 | 415 | Improved or stable | [36,37,38,42,45,91,97,99,100] | |
| GROWTH | observational | I, II, IVA, VI | 0–58 | 628 | Limited improvement before 15 years of age | [37,45,70,101,102,103,104] |
| observational | I, II | 0.4–23.1 | 171 | No improvement | [40,105,106,107] |
Notes: uGAGs = urinary glycosaminoglycans, OSAs = obstructive sleep apneas, AHI = apnea hypopnea index, FEV1 = forced expiratory volume in the first second, FEV1% = percent predicted FEV1, FVC = forced vital capacity, MVV = maximal voluntary ventilation, ROM = range of motion, 6MWT = 6 min walking test, 12MWT = 12 min walking test, 3MSC = 3 min stair climbing, MPS-HAQ = MPS- health assessment questionnaire, CHAQ = childhood health assessment questionnaire, HAQ = health assessment questionnaire.