Enzyme replacement therapy for Mucopolysaccharidosis Type I among patients followed within the MPS Brazil Network

Abstract

Mucopolysaccharidosis type I (MPS I) is a rare lysosomal disorder caused by deficiency of alpha-L-iduronidase. Few clinical trials have assessed the effect of enzyme replacement therapy (ERT) for this condition. We conducted an exploratory, open-label, non-randomized, multicenter cohort study of patients with MPS I. Data were collected from questionnaires completed by attending physicians at the time of diagnosis (T1; n = 34) and at a median time of 2.5 years later (T2; n = 24/34). The 24 patients for whom data were available at T2 were allocated into groups: A, no ERT (9 patients; median age at T1 = 36 months; 6 with severe phenotype); B, on ERT (15 patients; median age at T1 = 33 months; 4 with severe phenotype). For all variables in which there was no between-group difference at baseline, a delta of ≥ ± 20% was considered clinically relevant. The following clinically relevant differences were identified in group B in T2: lower rates of mortality and reported hospitalization for respiratory infection; lower frequency of hepatosplenomegaly; increased reported rates of obstructive sleep apnea syndrome and hearing loss; and stabilization of gibbus deformity. These changes could be due to the effect of ERT or of other therapies which have also been found more frequently in group B. Our findings suggest MPS I patients on ERT also receive a better overall care. ERT may have a positive effect on respiratory morbidity and overall mortality in patients with MPS I. Additional studies focusing on these outcomes and on other therapies should be performed.

Survival in idursulfase‐treated and untreated patients with mucopolysaccharidosis type II: data from the Hunter Outcome Survey (HOS)

“…Only limited data are available for MPS I and MPS VI (Dornelles et al 2014;Giugliani et al 2014); whilst these small studies indicate a possible survival benefit with ERT, our analysis is the first to show an impact in a large population of treated and untreated patients. Overall, despite the complexities of the data, our analysis demonstrates a survival benefit with intravenous idursulfase treatment in patients with MPS II.…”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…Some of these studies are the phase III extension studies and involve the same patients previously enrolled in the Phase III trials [36][37][38][39]71,96,114]. The others are mostly observational studies conducted in a single center on a limited number of cases, or studies performed on data extracted from disease registries [29,34,37,[40][41][42][43][44][47][48][49][50][51][52]70,74,77,84,85,97,116]. Disease registries are a helpful tool to collect data on rare diseases and there is now a huge number of disease registries available for many rare diseases.…”

Mucopolysaccharidosis type I, II and VI and response to enzyme replacement therapy: Results from a single-center case series study

“…A study with 24 MPS I patients (24), also reported deaths in 7 patients during ERT. The main causes of death in our case series were respiratory problems such as pneumonia, complications of anesthesia, and pulmonary hypertension, in line with previous reports (23,24).…”