Journal Article

Long-term outcomes of elosulfase alfa enzyme replacement therapy in adults with MPS IVA: a sub-analysis of the Morquio A Registry Study (MARS)

Lail, Alice, Ellaway, Carolyn, Hinds, David, Mitchell, John J., Magner, Martin, Stepien, Karolina M., Bober, Michael B., Bhattacharya, Kaustuv, Guffon, Nathalie, Reisewitz, Pascal, Hunt, Abigail, Murphy, Elaine, Lin, Shuan-Pei, Campeau, Philippe M., Burton, Barbara K.

2025

Overview

Background Mucopolysaccharidosis (MPS) IVA is a rare disease with substantial, multisystemic morbidity. We assessed real-world safety and effectiveness of the enzyme replacement therapy (ERT) elosulfase alfa in patients with MPS IVA in the multinational, observational Morquio A Registry Study (MARS) who initiated ERT in adulthood (aged ≥ 18 years). Methods Patients were enrolled between September 2014 and February 2022; urinary keratan sulfate (uKS), 6-minute walk test (6MWT) distance, forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), EuroQoL-5D-5L (EQ-5D-5L) score, and safety were assessed during routine care. Results As of February 13, 2022, 90 patients who initiated ERT had enrolled (median exposure: 5.6 years; median age at first ERT: 27.8 years). Reductions from baseline in uKS levels were sustained over mean follow-up of 5.4 years (mean percent change: -52.9%; p  < 0.0001). In patients with available data, mean change in 6MWT distance was + 15.8 m ( p  = 0.3627) over a mean follow-up of 5.8 years. FEV 1 and FVC remained stable over mean follow-up of 5.3 years (mean change: 0.0 L for both). The mean change from baseline in EQ-5D-5L index score was + 0.1 after 1 year of treatment. Thirty-four patients (39.5%) had ≥ 1 adverse event (AE), 23 patients (26.7%) had ≥ 1 serious AE, and 10 (11.6%) had ≥ 1 drug-related AE (infusion-related reactions [ n  = 3; 3.5%], pyrexia [ n  = 2; 2.3%]). Eight deaths occurred; none were deemed treatment related. Conclusions Real-world data collected from MARS suggest that patients with MPS IVA who initiated ERT in adulthood remained stable over 7 years of follow-up. No new safety signals were identified.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Adolescent / Adult / Analysis / Care and treatment / Chondroitinsulfatases - therapeutic use / Clinical outcomes / Drug therapy / Elosulfase alfa / Enzyme Replacement Therapy - methods / Enzymes / Female / Health aspects / Human Genetics / Humans / Male / Medical research / Medicine / Medicine & Public Health / Medicine, Experimental / Middle Aged / Mucopolysaccharidosis / Mucopolysaccharidosis IV - drug therapy / Mucopolysaccharidosis IVA / Patient-reported outcomes / Pharmacology/Toxicology / Physiological aspects / Real-world evidence / Registries / Registries (in medicine) / Treatment Outcome / Young Adult