Clinical characteristics and real-world outcomes in patients with mucopolysaccharidosis II over 18 years: final report of the Hunter Outcome Survey.

BACKGROUND

Mucopolysaccharidosis II (MPS II) is a rare, progressive, X-linked lysosomal storage disease. Enzyme replacement therapy (ERT) with intravenous (IV) idursulfase has been approved for the treatment of patients with MPS II since 2005. The Hunter Outcome Survey (HOS; NCT03292887) was established as a condition of approval to monitor the long-term safety and effectiveness of idursulfase. Here, we report the final results from HOS.

METHODS

HOS was a multicenter, long-term, observational registry that enrolled patients with a biochemically and/or genetically confirmed diagnosis of MPS II who were untreated or treated with idursulfase and/or bone marrow transplant. Patients were enrolled prospectively (alive at enrollment) and retrospectively (deceased at enrollment). For prospectively enrolled patients, it was requested that data from routine examinations were recorded after each follow-up visit and/or a minimum of every 6 months. The safety population (SP) included patients who received at least one dose of idursulfase and were alive at HOS entry. The treatment outcomes population (TOP) included patients who received at least one dose of idursulfase and were alive at HOS entry, excluding patients who received a bone marrow transplant, patients for whom an informed consent form could not be generated by the center, and patients with a missing date of birth. Safety and effectiveness endpoints were analyzed with descriptive statistics.

RESULTS

In total, 1332 patients were enrolled in HOS. For patients in the SP (N = 1014), the median (10th percentile, 90th percentile) age at initiation of ERT with idursulfase was 5.7 (1.6, 18.1) years, ranging from 0.0 to 65.5 years. In the TOP (N = 989), a consistent and sustained decline in urinary glycosaminoglycan levels, trends of sustained improvements in walking capacity and left ventricular mass index, and reductions in liver and spleen size were observed. Treated patients also demonstrated a median increase in survival time of approximately 10 years and a 57.9 % lower risk of death compared with an unmatched cohort of untreated patients. In the SP, 691 patients (68.1 %) experienced at least one adverse event and 269 (26.5 %) experienced at least one infusion-related reaction (IRR); most were mild or moderate in severity. There was no relationship observed between anti-drug antibody status and IRR rates.

CONCLUSION

Data from HOS, collected for over 18 years, represent the largest dataset of patients with MPS II to date. The effectiveness and safety profile of idursulfase support its use for the long-term treatment of patients with MPS II.