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Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry

BACKGROUND: Niemann-Pick disease Type C (NP-C) is a rare, progressive neurodegenerative disorder characterized by progressive neurodegeneration and premature death. We report data at closure of the NPC Registry that describes the natural history, disease course and treatment experience of NP-C patie...

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Autores principales: Patterson, Marc C., Mengel, Eugen, Vanier, Marie T., Moneuse, Patrick, Rosenberg, Daniel, Pineda, Mercedes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183679/
https://www.ncbi.nlm.nih.gov/pubmed/32334605
http://dx.doi.org/10.1186/s13023-020-01363-2
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author Patterson, Marc C.
Mengel, Eugen
Vanier, Marie T.
Moneuse, Patrick
Rosenberg, Daniel
Pineda, Mercedes
author_facet Patterson, Marc C.
Mengel, Eugen
Vanier, Marie T.
Moneuse, Patrick
Rosenberg, Daniel
Pineda, Mercedes
author_sort Patterson, Marc C.
collection PubMed
description BACKGROUND: Niemann-Pick disease Type C (NP-C) is a rare, progressive neurodegenerative disorder characterized by progressive neurodegeneration and premature death. We report data at closure of the NPC Registry that describes the natural history, disease course and treatment experience of NP-C patients in a real-world setting. METHODS: The NPC Registry was a prospective observational cohort study that ran between September 2009 and October 2017. Patients with a confirmed diagnosis of NP-C were enrolled regardless of treatment status. All patients underwent clinical assessments and medical care as determined by their physicians; data were collected through a secure internet-based portal. RESULTS: At closure on October 19, 2017, 472 patients from 22 countries were enrolled in the NPC Registry. Mean (standard deviation) age at enrollment was 21.2 (15.0) years, and 51.9% of patients were male. First neurological symptom onset occurred during the early-infantile (< 2 years), late-infantile (2 to < 6 years), juvenile (6 to < 15 years), or adolescent/adult (≥ 15 years) periods in 13.5, 25.6, 31.8, and 29.1% of cases, respectively. The most frequent neurological manifestations prior to enrollment included ataxia (67.9%), vertical supranuclear gaze palsy (67.4%), dysarthria (64.7%), cognitive impairment (62.7%), dysphagia (49.1%), and dystonia (40.2%). During infancy, splenomegaly and hepatomegaly were frequent (n = 199/398 [50%] and n = 147/397 [37.0%], respectively) and persisted in most affected patients. Of the 472 enrolled patients, 241 were continuously treated with miglustat during the NPC Registry observation period, of whom 172 of these 241 patients were treated continuously for ≥12 months. A composite disability score that assesses impairment of ambulation, manipulation, language, and swallowing was highest in the early-infantile population and lowest in the adolescent/adult population. Among the continuous miglustat therapy population, 70.5% of patients had improved or had stable disease (at least 3 of the 4 domains having a decreased or unchanged score between enrollment and last follow-up). The NPC Registry did not identify any new safety signals associated with miglustat therapy. CONCLUSIONS: The profiles of clinical manifestations in the final NPC Registry dataset agreed with previous clinical descriptions. Miglustat therapy was associated with a stabilization of neurological manifestations in most patients. The safety and tolerability of miglustat therapy was consistent with previous reports.
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spelling pubmed-71836792020-04-29 Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry Patterson, Marc C. Mengel, Eugen Vanier, Marie T. Moneuse, Patrick Rosenberg, Daniel Pineda, Mercedes Orphanet J Rare Dis Research BACKGROUND: Niemann-Pick disease Type C (NP-C) is a rare, progressive neurodegenerative disorder characterized by progressive neurodegeneration and premature death. We report data at closure of the NPC Registry that describes the natural history, disease course and treatment experience of NP-C patients in a real-world setting. METHODS: The NPC Registry was a prospective observational cohort study that ran between September 2009 and October 2017. Patients with a confirmed diagnosis of NP-C were enrolled regardless of treatment status. All patients underwent clinical assessments and medical care as determined by their physicians; data were collected through a secure internet-based portal. RESULTS: At closure on October 19, 2017, 472 patients from 22 countries were enrolled in the NPC Registry. Mean (standard deviation) age at enrollment was 21.2 (15.0) years, and 51.9% of patients were male. First neurological symptom onset occurred during the early-infantile (< 2 years), late-infantile (2 to < 6 years), juvenile (6 to < 15 years), or adolescent/adult (≥ 15 years) periods in 13.5, 25.6, 31.8, and 29.1% of cases, respectively. The most frequent neurological manifestations prior to enrollment included ataxia (67.9%), vertical supranuclear gaze palsy (67.4%), dysarthria (64.7%), cognitive impairment (62.7%), dysphagia (49.1%), and dystonia (40.2%). During infancy, splenomegaly and hepatomegaly were frequent (n = 199/398 [50%] and n = 147/397 [37.0%], respectively) and persisted in most affected patients. Of the 472 enrolled patients, 241 were continuously treated with miglustat during the NPC Registry observation period, of whom 172 of these 241 patients were treated continuously for ≥12 months. A composite disability score that assesses impairment of ambulation, manipulation, language, and swallowing was highest in the early-infantile population and lowest in the adolescent/adult population. Among the continuous miglustat therapy population, 70.5% of patients had improved or had stable disease (at least 3 of the 4 domains having a decreased or unchanged score between enrollment and last follow-up). The NPC Registry did not identify any new safety signals associated with miglustat therapy. CONCLUSIONS: The profiles of clinical manifestations in the final NPC Registry dataset agreed with previous clinical descriptions. Miglustat therapy was associated with a stabilization of neurological manifestations in most patients. The safety and tolerability of miglustat therapy was consistent with previous reports. BioMed Central 2020-04-25 /pmc/articles/PMC7183679/ /pubmed/32334605 http://dx.doi.org/10.1186/s13023-020-01363-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Patterson, Marc C.
Mengel, Eugen
Vanier, Marie T.
Moneuse, Patrick
Rosenberg, Daniel
Pineda, Mercedes
Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
title Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
title_full Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
title_fullStr Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
title_full_unstemmed Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
title_short Treatment outcomes following continuous miglustat therapy in patients with Niemann-Pick disease Type C: a final report of the NPC Registry
title_sort treatment outcomes following continuous miglustat therapy in patients with niemann-pick disease type c: a final report of the npc registry
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183679/
https://www.ncbi.nlm.nih.gov/pubmed/32334605
http://dx.doi.org/10.1186/s13023-020-01363-2
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