Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa

Hughes, D.A.; Giugliani, Roberto; Guffon, Nathalie; Jones, Simon A.; Mengel, Karl Eugen; Parini, Rossella; Matousek, Robert; Hawley, Sara M.; Quartel, Adrian

doi:10.1186/s13023-017-0634-0

Cited by 28 publications

(36 citation statements)

References 20 publications

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“…*P = 0.001 clinical trial results are also similar to our findings of 6MWT improvements or maintenance over a period of up to 7 years. In addition, we observed improvements in MPS-HAQ outcomes, similar to those seen in the Phase 3 clinical trial [20,24]. It should be kept in mind that 6MWT distance increases with age and height in children, which may partly explain long-term increases in the test in younger patients [25,26].…”

Section: Discussionsupporting

confidence: 79%

Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study

Moisan

Iannuzzi

Maranda

et al. 2020

Orphanet J Rare Dis

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Background Morquio A syndrome is a rare, autosomal recessive, progressively debilitating disorder, with multi-system impairments and high medical burden. Quebec, Canada has a large Morquio A population, which is considered unique due to the presence of founder pathogenic variants. The objectives of this study were to document the genetic and clinical heterogeneity of patients with Morquio A in Quebec, to better characterize the phenotype of those with the French Canadian founder pathogenic variant (NM_000512.5: c.1171A>G, p.Met391Val), and to describe the natural history of the patients treated with elosulfase alfa enzyme replacement therapy. Patients with Morquio A were genotyped for pathogenic variants in the lysosomal enzyme N-acetylgalactosamine-6-sulfatase. Clinical data were retrospectively collected from medical charts of patients and included medical history, height, physical examination, respiratory function tests, electrocardiogram, echocardiogram, endurance in the 6-min walk test (6MWT), and activities of daily living (ADL) as assessed by the Mucopolysaccharidosis Health Assessment Questionnaire (MPS-HAQ). Longitudinal data were collected retrospectively and prospectively for patients treated with elosulfase alfa. Results A total of 33 patients, aged 5–63 years, were included in the analysis. Patients with the founder pathogenic variant (n = 17) generally exhibited a non-classical form of Morquio A. As compared with patients with a non-founder pathogenic variant (n = 16), these patients were generally taller, had greater endurance and were better able to perform ADL. However, they still had significant musculoskeletal disease. Most of the 26 patients treated with elosulfase alfa, regardless of pathogenic variant, showed improvements in endurance and ADL. After 5 to 12 months of treatment, the mean improvement from baseline in the 6MWT was 23% and 10 of 14 patients improved in at least one MPS-HAQ domain. Endurance and ADL generally continued to improve or maintained stable in the long term (up to 7 years). Four out of 19 treated patients with echocardiogram data at follow-up showed progression of cardiac disease. Conclusions In Quebec, Canada, Morquio A frequently manifests as a non-classical form of the syndrome due to a founder effect. Patients treated with elosulfase alfa generally show long-term improvement or stability in endurance and function, regardless of pathogenic variant.

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Section: Discussionsupporting

confidence: 79%

Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study

Moisan

Iannuzzi

Maranda

et al. 2020

Orphanet J Rare Dis

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“…Overall, these findings do not suggest that ERT was useful in achieving significant skeletal changes, whereas it did have an effect on functional capacity, including endurance, balance, and activities of daily living. These findings are not surprising as ERT with elosulfase alfa has been shown to improve endurance and exercise capacity [20,35,47], partially due to improved respiratory function and oxygen utilization [13].…”

Section: Physical and Functional Statusmentioning

confidence: 87%

Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings

et al. 2020

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Enzyme replacement therapy (ERT) is one of the available therapies for mucopolysaccharidosis (MPS). This study presents a follow-up of two siblings with MPS IVA (Morquio A disease) that received ERT. Both siblings received weekly intravenous infusions of elosulfase alfa for 4.5 years. One sibling (patient 1, P1; male) started therapy at 54 months of age, and the other sibling (patient 2, P2; female) started at 11 months of age. ERT was well-tolerated. In comparison to P1, P2's growth curves deviated less from the norm. The orthopedic deformities of P1 were more severe than those of P2 and required several surgical corrections. P1's sleep test at 48 months revealed obstructive sleep apnea, while by the age of 102 months, parameters were normal. P2 never had sleep apnea. Only P1 demonstrated ear, nose, and throat clinical illnesses. In comparison to P1, P2's physical function was better maintained. In conclusion, ERT was safe in both patients during a 4.5-year follow-up. Although the typical characteristics of this disease were similar in both patients, P1 had a complex clinical course in comparison to P2, which influenced function and quality of life. Therefore, in order to make the most of ERT, it may be more beneficial when initiated at a relatively young age.

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“…In a Phase III clinical trial, patients who received intravenous elosulfase alfa at a dose of 2 mg/kg/week experienced reductions in urinary levels of keratan sulphate (a pharmacodynamic biomarker for the disease) [30]. Elosulfase alfa has been shown to improve endurance and exercise capacity (as measured by the 6MWT), which may in part relate to improved respiratory function and oxygen utilization [30, 33–36]. A trend for improvement in performance of ADL was also observed in a long-term extension study.…”

Section: Resultsmentioning

confidence: 99%

“…A trend for improvement in performance of ADL was also observed in a long-term extension study. The findings suggest that long-term elosulfase alpha ERT is associated with partial recovery of functional abilities, improving Morquio A patients’ abilities to perform ADL [36]. The evidence for the effect of elosulfase alfa on bone is currently limited and further research is required.…”

Section: Resultsmentioning

confidence: 99%

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

Akyol

Alden

Amartino

et al. 2019

Orphanet J Rare Dis

117

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Introduction Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is an autosomal recessive lysosomal storage disorder (LSD) caused by deficiency of the N -acetylgalactosamine-6-sulfatase (GALNS) enzyme, which impairs lysosomal degradation of keratan sulphate and chondroitin-6-sulphate. The multiple clinical manifestations of MPS IVA present numerous challenges for management and necessitate the need for individualised treatment. Although treatment guidelines are available, the methodology used to develop this guidance has come under increased scrutiny. This programme was conducted to provide evidence-based, expert-agreed recommendations to optimise management of MPS IVA. Methods Twenty six international healthcare professionals across multiple disciplines, with expertise in managing MPS IVA, and three patient advocates formed the Steering Committee (SC) and contributed to the development of this guidance. Representatives from six Patient Advocacy Groups (PAGs) were interviewed to gain insights on patient perspectives. A modified-Delphi methodology was used to demonstrate consensus among a wider group of healthcare professionals with experience managing patients with MPS IVA and the manuscript was evaluated against the validated Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument by three independent reviewers. Results A total of 87 guidance statements were developed covering five domains: (1) general management principles; (2) recommended routine monitoring and assessments; (3) disease-modifying interventions (enzyme replacement therapy [ERT] and haematopoietic stem cell transplantation [HSCT]); (4) interventions to support respiratory and sleep disorders; (5) anaesthetics and surgical interventions (including spinal, limb, ophthalmic, cardio-thoracic and ear-nose-throat [ENT] surgeries). Consensus was reached on all statements after two rounds of voting. The overall guideline AGREE II assessment score obtained for the development of the guidance was 5.3/7 (where 1 represents the lowest quality and 7 represents the highest quality of guidance). Conclusion This manuscript provides evidence- and consensus-based recommendations for the management of patients with MPS IVA and is for use by healthcare professionals that manage the holistic care of patients with the intention to improve clinical- and patient-reported outcomes and enhance patient quality of life. It is recognised that the guidance provided represents a point in time and further research is required to address current knowledge and evidence gaps. Electronic supplementary material The online version of this article (10.1186/s13023-019-1074-9) contains supplementary material, which is available to authorized users.

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Clinical outcomes in a subpopulation of adults with Morquio A syndrome: results from a long-term extension study of elosulfase alfa

Cited by 28 publications

References 20 publications

Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study

Clinical characteristics of patients from Quebec, Canada, with Morquio A syndrome: a longitudinal observational study

Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings

Recommendations for the management of MPS IVA: systematic evidence- and consensus-based guidance

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