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Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C : an observational cohort study

Patterson, Marc C.; Mengel, Eugen; Vanier, Marie T.; Schwierin, Barbara; Muller, Audrey; Cornelisse, Peter; Pineda, Mercè; , ; Puschmann, Andreas LU and Rask, Olof LU (2015) In Orphanet Journal of Rare Diseases 10. p.65-65
Abstract

BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat.

METHODS: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the... (More)

BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat.

METHODS: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption >28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if <3 scores were lower/unchanged between enrolment and last follow-up visit.

RESULTS: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (<2 years), 27 (32 %) had late-infantile (2 to <6 years), 30 (36 %) had juvenile (6 to <15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data.

CONCLUSIONS: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.

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1-Deoxynojirimycin, Adolescent, Adult, Child, Child, Preschool, Cohort Studies, Disease Progression, Enzyme Inhibitors, Female, Humans, Male, Niemann-Pick Disease, Type C, Prospective Studies, Treatment Outcome, Young Adult, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
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Orphanet Journal of Rare Diseases
volume
10
pages
65 - 65
publisher
BioMed Central
external identifiers
  • scopus:84931039342
ISSN
1750-1172
DOI
10.1186/s13023-015-0284-z
language
English
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yes
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ad0273b0-a722-43af-9025-0e43fd805476
date added to LUP
2017-04-19 18:32:02
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2017-11-19 04:39:28
@article{ad0273b0-a722-43af-9025-0e43fd805476,
  abstract     = {<p>BACKGROUND: Niemann-Pick disease type C (NP-C) is a rare neurovisceral disease characterised by progressive neurological degeneration, where the rate of neurological disease progression varies depending on age at neurological onset. We report longitudinal data on functional disease progression and safety observations in patients in the international NPC Registry who received continuous treatment with miglustat.</p><p>METHODS: The NPC Registry is a prospective observational cohort of NP-C patients. Enrolled patients who received ≥1 year of continuous miglustat therapy (for ≥90 % of the observation period, with no single treatment interruption &gt;28 days) were included in this analysis. Disability was measured using a scale rating the four domains, ambulation, manipulation, language and swallowing from 0 (normal) to 1 (worst). Neurological disease progression was analysed in all patients based on: 1) annual progression rates between enrolment and last follow up, and; 2) categorical analysis with patients categorised as 'improved/stable' if ≥3/4 domain scores were lower/unchanged, and as 'progressed' if &lt;3 scores were lower/unchanged between enrolment and last follow-up visit.</p><p>RESULTS: In total, 283 patients were enrolled from 28 centers in 13 European countries, Canada and Australia between September 2009 and October 2013; 92 patients received continuous miglustat therapy. The mean (SD) miglustat exposure during the observation period (enrolment to last follow-up) was 2.0 (0.7) years. Among 84 evaluable patients, 9 (11 %) had early-infantile (&lt;2 years), 27 (32 %) had late-infantile (2 to &lt;6 years), 30 (36 %) had juvenile (6 to &lt;15 years) and 18 (21 %) had adolescent/adult (≥15 years) onset of neurological manifestations. The mean (95%CI) composite disability score among all patients was 0.37 (0.32,0.42) at enrolment and 0.44 (0.38,0.50) at last follow-up visit, and the mean annual progression rate was 0.038 (0.018,0.059). Progression of composite disability scores appeared highest among patients with neurological onset during infancy or childhood and lowest in those with adolescent/adult-onset. Overall, 59/86 evaluable patients (69 %) were categorized as improved/stable and the proportion of improved/stable patients increased with age at neurological onset. Safety findings were consistent with previous data.</p><p>CONCLUSIONS: Disability status was improved/stable in the majority of patients who received continuous miglustat therapy for an average period of 2 years.</p>},
  author       = {Patterson, Marc C. and Mengel, Eugen and Vanier, Marie T. and Schwierin, Barbara and Muller, Audrey and Cornelisse, Peter and Pineda, Mercè and ,  and Puschmann, Andreas and Rask, Olof},
  issn         = {1750-1172},
  keyword      = {1-Deoxynojirimycin,Adolescent,Adult,Child,Child, Preschool,Cohort Studies,Disease Progression,Enzyme Inhibitors,Female,Humans,Male,Niemann-Pick Disease, Type C,Prospective Studies,Treatment Outcome,Young Adult,Journal Article,Research Support, N.I.H., Extramural,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {05},
  pages        = {65--65},
  publisher    = {BioMed Central},
  series       = {Orphanet Journal of Rare Diseases},
  title        = {Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C : an observational cohort study},
  url          = {http://dx.doi.org/10.1186/s13023-015-0284-z},
  volume       = {10},
  year         = {2015},
}