Clinical effectiveness of enzyme replacement therapy with galsulfase in mucopolysaccharidosis type VI treatment: Systematic review

Abstract

Introduction: Mucopolysaccharidosis VI is a rare disease characterized by the arylsulfatase B enzyme deficiency, which is responsible for different clinical manifestations. The treatment consists of enzyme replacement therapy with intravenous administration of galsulfase. Objective: Evaluate the effectiveness of the enzyme replacement therapy with galsulfase for the mucopolysaccharidosis VI treatment. Method: Systematic review of observational studies. The databases of PubMed, Cochrane Library, Lilacs, and Journal of Inherited Metabolic Disease were reviewed. The selection of studies, data mining, and methodological quality assessment were independently conducted by two authors. Results: Eighteen studies fulfilled the inclusion criteria. Two studies were cohorts, one was longitudinal study, one was cross-sectional, one was a case-control, eight were case series, and five were case reports. A total of 362 participants with mucopolysaccharidosis type VI were evaluated, and 14 different outcomes related to the treatment effect were identified. Seven outcomes showed positive results, characterized by the patient survival, quality of life, respiratory function, joint mobility, physical resistance, reduction of urinary glycosaminoglycans, and growth. The hearing function and the cognitive development were stable after the treatment. Other outcomes related to the cardiac function, visual acuity, sleep apnea, and the size of the liver and spleen presented inconclusive outcomes. Concerning safety, light adverse reactions of hypersensitivity were reported. Conclusion: This review provided a broader panoramic view of the outcomes related to mucopolysaccharidosis type VI. Regardless of the inherent limitations of observational studies, the outcomes indicate that the enzyme replacement therapy has a positive effect on most of the outcomes associated to the disease.

The Impact of Excluding Nonrandomized Studies From Systematic Reviews in Rare Diseases: “The Example of Meta-Analyses Evaluating the Efficacy and Safety of Enzyme Replacement Therapy in Patients With Mucopolysaccharidosis”

“…They did not select other study designs Brunelli et al (2016) They selected one randomized study. They did not combine results from different study designs Gomes et al (2019) The effectiveness of ERT was identified by a qualitative assessment of each study report. The outcomes were classified as primary and substitutive according to the authors' assessment MPS, muchopolysaccharidosis; ERT, enzyme replacement therapy; GRADE, grading of recommendations assessment, development and evaluation; HSCT, hematopoietic stem cell transplant; 6-MWT, 6-min walk test.…”

Hearing Loss in Mucopolysaccharidoses: Current Knowledge and Future Directions

“…Treatment options vary depending on the MPS subtype. ERT is the most common treatment for MPS, with approved therapies available for [51,52], MPS II [30], MPS IVA [85][86][87], MPS VI [37], and MPS VII [103,104]. Research on the effects of ERT on audiological function has been inconclusive [53].…”

“…Research on the effects of ERT on audiological function has been inconclusive [53]. While case reports on MPS IVA [88] and MPS VI [38,39] have described hearing improvement after ERT, studies on MPS I [21] and MPS VI [37] have described no change in audiological function after ERT. A MPS II murine model found that ERT was able to improve the conductive component, but was unable to ameliorate the sensorineural component [31].…”

“…Recurrent acute otitis media are a common problem in patients with MPS VI [96]. Most patients with MPS VI suffer from mild to moderate conductive hearing loss [10,11,37,96]. A recent retrospective study of five patients with MPS VI reported that, while conductive hearing loss is common, it seems to be temporary and can be treated through surgical interventions such as tympanostomy tube placement [97].…”

“…Without the presence of any otolaryngologic interventions such as tympanostomy tube placement, hearing issues can progress and lead to severe or permanent hearing loss [97]. As for the ERT effects on hearing in patients with MPS VI, the results are still inconclusive [37][38][39][40]53]. Previous studies have indicated an unchanging hearing status after ERT in some patients, whereas other studies have indicated hearing improvement [38][39][40], even in the patient with sensorineural hearing loss.…”