Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy

Abstract

BackgroundPompe disease is a rare lysosomal storage disorder characterized by muscle weakness and wasting. The majority of adult patients have slowly progressive disease, which gradually impairs mobility and respiratory function and may lead to wheelchair and ventilator dependency. It is as yet unknown to what extent the disease reduces the life span of these patients. Our objective was to determine the survival of adults with Pompe disease not receiving ERT and to identify prognostic factors associated with survival.MethodsData of 268 patients were collected in a prospective international observational study conducted between 2002 and 2009. Survival analyses from time of diagnosis and from time of study entry were performed using Kaplan-Meier curves and Cox-proportional-hazards regression.ResultsMedian age at study entry was 48 years (range 19-79 years). Median survival after diagnosis was 27 years, while median age at diagnosis was 38 years. During follow-up, twenty-three patients died prior to ERT, with a median age at death of 55 (range 23-77 years). Use of wheelchair and/or respiratory support and patients' score on the Rotterdam Handicap Scale (RHS) were identified as prognostic factors for survival. Five-year survival for patients without a wheelchair or respiratory support was 95% compared to 74% in patients who were wheelchair-bound and used respiratory support. In a Dutch subgroup of 99 patients, we compared the observed number of deaths to the expected number of deaths in the age- and sex-matched general population. During a median follow-up of 2.3 years, the number of deaths among the Dutch Pompe patients was higher than the expected number of deaths in the general population.ConclusionOur study shows for the first time that untreated adults with Pompe disease have a higher mortality than the general population and that their levels of disability and handicap/participation are the most important factors associated with mortality. These results may be of relevance when addressing the effect of ERT or other potential treatment options on survival.

Respiratory function in late-onset Pompe disease patients receiving long-term enzyme replacement therapy for more than 48 months

“…Late-onset Pompe disease is characterized by a progressive weakness of both limbgirdle and respiratory muscles. Respiratory failure is the leading cause of death in late-onset Pompe patients [3], but prognosis regarding respiratory impairment is highly complicated by the large interindividual variability in these patients. There is no clear correlation between severity of limb-girdle and respiratory involvement; one-third of adult patients require ventilator support while they are still able to walk [4].…”

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“…Под СПКМ понимали слабость проксимальных мышц плечевого пояса и рук, аксиальных мышц, мышц та-зового пояса и бедер [1][2][3]. ГиперКК определяли как повышение уровня креатинкиназы (КК) в 2 раза относительно верхней границы нормы (для женщин < 180 МЕ / л, для мужчин < 200 МЕ / л).…”

“…Частой причиной обращения к врачу у боль-шинства больных является слабость аксиальных и проксимальных скелетных мышц. Как правило, причина смерти пациентов с БППН связана с разви- тием дыхательной недостаточности в результате сла-бости дыхательной мускулатуры [2]. Разработка и вне-дрение в практику ферментной заместительной терапии диктуют необходимость повышения осведом-ленности о заболевании специалистов различных ме-дицинских специальностей.…”

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

“…Without treatment, patients with the infantile form will not survive their first year of life. Adult patients can survive until their 60s or 70s, but their average life expectancy is still much shorter than in the general population [3]. Patients with Pompe disease have a health-related quality of life (hrQoL) of 0.72 (based on the Euroqol 5D), which is lower than the Dutch average of 0.87 [4].…”