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

Abstract

Mucopolysaccharidosis type II (MPS II; Hunter syndrome; OMIM 309900) is a life-limiting, multisystemic disease with varying presentation and severity. Enzyme replacement therapy with intravenous idursulfase (EC 3.1.6.13) has been available since 2006. Data from the Hunter Outcome Survey (July 2016) were used to compare survival in idursulfase-treated (n = 800) and untreated (n = 95) male patients followed prospectively in this multinational, observational registry. Median age at symptom onset was similar for the treated and untreated groups (1.6 and 1.5 years, respectively), as was median age at diagnosis (3.3 and 3.2 years) and the proportion of patients with cognitive impairment (58.0%; 57.9%). 33.0 (30.4, 38.4) years in treated patients and 21.2 (16.1, 31.5) years in untreated patients; median follow-up time from birth to death or last visit was 13.0 and 15.1 years, respectively. A Cox model adjusted for treatment status, cognitive impairment, region and age at diagnosis indicated a 54% lower risk of death in treated compared with untreated patients: hazard ratio (HR), 0.46 (95% CI: 0.29, 0.72). Patients with cognitive impairment had nearly a fivefold higher risk of death than those without (HR, 4.84 [3.13, 7.47]). This analysis in a large population of patients with MPS II indicates for the first time that idursulfase treatment is associated with increased survival.

Clinical outcomes in idursulfase-treated patients with mucopolysaccharidosis type II: 3-year data from the hunter outcome survey (HOS)

“…Improvements in clinical parameters such as forced vital capacity (FVC) and distance walked in the 6-min walk test (6MWT), as well as decreases in liver and spleen size (as measured by magnetic resonance imaging) and urinary GAG (uGAG) levels have been demonstrated in clinical trials of intravenous idursulfase in patients with MPS II [ 7 – 9 ]. A recent analysis of data from the Hunter Outcome Survey (HOS) also demonstrated improved survival in patients who received idursulfase compared with those who were untreated [ 10 ]. In addition, idursulfase has been shown to be generally well tolerated, with a safety profile similar to that reported for ERT in patients with other mucopolysaccharidoses [ 7 – 9 , 11 – 14 ].…”

Anesthesia Risk and the Mucopolysaccharidoses: A Challenging and Changing Landscape

“…Lastly, recently data from the Hunter outcome study looking at survival in MPS II patients who were treated and those not treated with ERT showed a greater length of survival in those treated with ERT. 46 This article showed a 10-year difference in those treated with ERT, again suggesting a beneficial effect on the cardiorespiratory system.…”

“…There is no doubt that HSCT and to a lesser extent ERT have proved successful in prolonging survival in MPS patients, but it must be said that these patients are left with a considerable burden of disease. 29,46 The success of treatment has reduced the number of severely affected children presenting for anesthesia and surgery and it could be said that the child with Hurler syndrome or an MPS disorder is no longer the worst airway problem in pediatrics but that the most severe airway challenges have been successfully transferred into later life. Patients either post-HSCT or ERT patients may present in the late teenage years or indeed in the 20s or 30s for surgery for significant cardiac valvular lesions, spinal surgery to the craniocervical or thoracolumbar junction, corneal surgery, or airway surgery for severe OSA.…”

Hunter syndrome with persistent thrombocytopenia

“…Splenectomy can be used as desperate measure in unusual non-responding situation. The definitive treatment for MPS II is enzyme replacement therapy and is available from 2006 and is associated with increased survival outcomes 7. One family with MPS II has been reported earlier with NK cell and B cell deficiencies 8.…”