Cargando…

Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study

BACKGROUND: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. METHODS: Patients in this open-label sing...

Descripción completa

Detalles Bibliográficos
Autores principales: de Vries, Juna M, van der Beek, Nadine AME, Hop, Wim CJ, Karstens, Francois PJ, Wokke, John H, de Visser, Marianne, van Engelen, Baziel GM, Kuks, Jan BM, van der Kooi, Anneke J, Notermans, Nicolette C, Faber, Catharina G, Verschuuren, Jan JGM, Kruijshaar, Michelle E, Reuser, Arnold JJ, van Doorn, Pieter A, van der Ploeg, Ans T
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519647/
https://www.ncbi.nlm.nih.gov/pubmed/23013746
http://dx.doi.org/10.1186/1750-1172-7-73
_version_ 1782252707359227904
author de Vries, Juna M
van der Beek, Nadine AME
Hop, Wim CJ
Karstens, Francois PJ
Wokke, John H
de Visser, Marianne
van Engelen, Baziel GM
Kuks, Jan BM
van der Kooi, Anneke J
Notermans, Nicolette C
Faber, Catharina G
Verschuuren, Jan JGM
Kruijshaar, Michelle E
Reuser, Arnold JJ
van Doorn, Pieter A
van der Ploeg, Ans T
author_facet de Vries, Juna M
van der Beek, Nadine AME
Hop, Wim CJ
Karstens, Francois PJ
Wokke, John H
de Visser, Marianne
van Engelen, Baziel GM
Kuks, Jan BM
van der Kooi, Anneke J
Notermans, Nicolette C
Faber, Catharina G
Verschuuren, Jan JGM
Kruijshaar, Michelle E
Reuser, Arnold JJ
van Doorn, Pieter A
van der Ploeg, Ans T
author_sort de Vries, Juna M
collection PubMed
description BACKGROUND: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. METHODS: Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA. RESULTS: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (−1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness. Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC. CONCLUSIONS: We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely.
format Online
Article
Text
id pubmed-3519647
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-35196472012-12-12 Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study de Vries, Juna M van der Beek, Nadine AME Hop, Wim CJ Karstens, Francois PJ Wokke, John H de Visser, Marianne van Engelen, Baziel GM Kuks, Jan BM van der Kooi, Anneke J Notermans, Nicolette C Faber, Catharina G Verschuuren, Jan JGM Kruijshaar, Michelle E Reuser, Arnold JJ van Doorn, Pieter A van der Ploeg, Ans T Orphanet J Rare Dis Research BACKGROUND: Enzyme replacement therapy (ERT) in adults with Pompe disease, a progressive neuromuscular disorder, is of promising but variable efficacy. We investigated whether it alters the course of disease, and also identified potential prognostic factors. METHODS: Patients in this open-label single-center study were treated biweekly with 20 mg/kg alglucosidase alfa. Muscle strength, muscle function, and pulmonary function were assessed every 3–6 months and analyzed using repeated-measures ANOVA. RESULTS: Sixty-nine patients (median age 52.1 years) were followed for a median of 23 months. Muscle strength increased after start of ERT (manual muscle testing 1.4 percentage points per year (pp/y); hand-held dynamometry 4.0 pp/y; both p < 0.001). Forced vital capacity (FVC) remained stable when measured in upright, but declined in supine position (−1.1 pp/y; p = 0.03). Muscle function did not improve in all patients (quick motor function test 0.7 pp/y; p = 0.14), but increased significantly in wheelchair-independent patients and those with mild and moderate muscle weakness. Relative to the pre-treatment period (49 patients with 14 months pre-ERT and 22 months ERT median follow-up), ERT affected muscle strength positively (manual muscle testing +3.3 pp/y, p < 0.001 and hand-held dynamometry +7.9 pp/y, p < 0.001). Its effect on upright FVC was +1.8 pp/y (p = 0.08) and on supine FVC +0.8 (p = 0.38). Favorable prognostic factors were female gender for muscle strength, and younger age and better clinical status for supine FVC. CONCLUSIONS: We conclude that ERT positively alters the natural course of Pompe disease in adult patients; muscle strength increased and upright FVC stabilized. Functional outcome is probably best when ERT intervention is timely. BioMed Central 2012-09-26 /pmc/articles/PMC3519647/ /pubmed/23013746 http://dx.doi.org/10.1186/1750-1172-7-73 Text en Copyright ©2012 de Vries et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
de Vries, Juna M
van der Beek, Nadine AME
Hop, Wim CJ
Karstens, Francois PJ
Wokke, John H
de Visser, Marianne
van Engelen, Baziel GM
Kuks, Jan BM
van der Kooi, Anneke J
Notermans, Nicolette C
Faber, Catharina G
Verschuuren, Jan JGM
Kruijshaar, Michelle E
Reuser, Arnold JJ
van Doorn, Pieter A
van der Ploeg, Ans T
Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study
title Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study
title_full Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study
title_fullStr Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study
title_full_unstemmed Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study
title_short Effect of enzyme therapy and prognostic factors in 69 adults with Pompe disease: an open-label single-center study
title_sort effect of enzyme therapy and prognostic factors in 69 adults with pompe disease: an open-label single-center study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3519647/
https://www.ncbi.nlm.nih.gov/pubmed/23013746
http://dx.doi.org/10.1186/1750-1172-7-73
work_keys_str_mv AT devriesjunam effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT vanderbeeknadineame effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT hopwimcj effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT karstensfrancoispj effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT wokkejohnh effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT devissermarianne effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT vanengelenbazielgm effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT kuksjanbm effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT vanderkooiannekej effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT notermansnicolettec effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT fabercatharinag effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT verschuurenjanjgm effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT kruijshaarmichellee effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT reuserarnoldjj effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT vandoornpietera effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy
AT vanderploeganst effectofenzymetherapyandprognosticfactorsin69adultswithpompediseaseanopenlabelsinglecenterstudy