Impact of enzyme replacement therapy on survival in adults with Pompe disease: results from a prospective international observational study

Abstract

BackgroundPompe disease is a rare metabolic myopathy for which disease-specific enzyme replacement therapy (ERT) has been available since 2006. ERT has shown efficacy concerning muscle strength and pulmonary function in adult patients. However, no data on the effect of ERT on the survival of adult patients are currently available. The aim of this study was to assess the effect of ERT on survival in adult patients with Pompe disease.MethodsData were collected as part of an international observational study conducted between 2002 and 2011, in which patients were followed on an annual basis. Time-dependent Cox’s proportional hazards models were used for univariable and multivariable analyses.ResultsOverall, 283 adult patients with a median age of 48 years (range, 19 to 81 years) were included in the study. Seventy-two percent of patients started ERT at some time during follow-up, and 28% never received ERT. During follow-up (median, 6 years; range, 0.04 to 9 years), 46 patients died, 28 (61%) of whom had never received ERT. After adjustment for age, sex, country of residence, and disease severity (based on wheelchair and ventilator use), ERT was positively associated with survival (hazard ratio, 0.41; 95% CI, 0.19 to 0.87).ConclusionThis prospective study was the first to demonstrate the positive effect of ERT on survival in adults with Pompe disease. Given the relatively recent registration of ERT for Pompe disease, these findings further support its beneficial impact in adult patients.

Guidelines for the diagnosis, treatment and clinical monitoring of patients with juvenile and adult Pompe disease

“…In the 18-month clinical trial conducted with the rhGAA enzyme in the late-onset PD form, there was an increase in the six minute walk test as well as stabilization of their pulmonary function 35 (A). The goals of rhGAA enzyme therapy depend on the stage of disease progression 35,36 (B), and include: • To slow down, stabilize or reverse disease progression;…”

“…inclusion and exclusion criteria for enzyme replacement therapy (table 5) The heterogeneity of symptoms and signs present in PD patients (Table 2), the intra-familial variability and different stages of PD have led to the characterization of different patient groups and created a clinical dilemma of when to put a patient on ERT with rhGAA. The groups currently are identified as newborns identified via newborn screening 8 ; asymptomatic patients with or without clinical signs of the disease 41 ; symptomatic PD patients 36 and patients with severe PD 9,10 ( Table 5). If the patient is confined to a wheelchair and using continuous invasive ventilation: ERT is recommended for 01 year, followed by evaluations to assess therapy effectiveness After 01 year of ERT, the multidisciplinary team will review the treatment case-by-case, especially for patients requiring continuous invasive ventilation ERT will be continued if there is stabilization or improvement of severe signs and symptoms ERT duration Annual reassessment to review the effectiveness of treatment Monitoring…”

Increased aortic stiffness and blood pressure in non-classic Pompe disease

“…Increased aortic stiffness and hypertension are both independent risk factors for cardiovascular disease and mortality (Mattace-Raso et al 2006; Verbeke et al 2011). It has been shown that patients with non-classic Pompe disease have improved survival when treated with ERT (Güngör et al 2013). Since cardiovascular diseases are more common at a higher age, Pompe patients will be more likely to develop cardiovascular diseases, as they owe their higher age to ERT.…”

Access to orphan drugs in western Europe: can more systematic policymaking really help to avoid different decisions about the same drug?

“…At the time of re-assessment, there was evidence that ERT dramatically improved life expectancy of infantile patients [5] and improved muscle strength and respiratory function in adult patients [6]. There were also indications that ERT may improve survival in adult patients, but little was known about its effect on hrQoL [7]. Ultimately, CVZ found that there was sufficient evidence that ERT increased survival in infants but limited evidence regarding its effectiveness in adults.…”