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

Marc C. Patterson, Eugen Mengel, Marie T. Vanier, Barbara Schwierin, Audrey Muller, Peter Cornelisse, Mercè Pineda, A. Amado-Fondo, Y. Amraoui, G. Andria, M. Arellano, B. Audoin, C. Azcona, C. Barr, J. Baruteau, C. Baumgartner, L. Bell, B. Bembi, K. Benneddif, G. Bernard & 31 others N. Bobocea, M. Bodzioch, T. Boettcher, M. Bonnan, P. Broue, A. Bruni, M. Caceres, R. Camino, E. Campbell, C. Cances, P. Cannell, J. Cesar, B. Chabrol, A. Chakrapani, R. Colao, A. Collet, T. Corsetti, A. Cousins, A. Covanis, T. Cox, J. M. Cuisset, A. Dardis, A. Das, P. Deegan, T. Dengler, F. Deodato, H. Derralynn, I. Di Donato, M. Di Rocco, G. Uziel, NPC Registry investigators

Research output: Contribution to journalArticle

44 Citations (Scopus)

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 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.

Original languageEnglish
Article number65
JournalOrphanet Journal of Rare Diseases
Volume10
Issue number1
DOIs
Publication statusPublished - May 28 2015

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Type C Niemann-Pick Disease
Neurologic Manifestations
Observational Studies
Registries
Cohort Studies
Therapeutics
Disease Progression
Age of Onset
miglustat
Observation
Safety
Deglutition
Rare Diseases

Keywords

  • Miglustat
  • Niemann-Pick disease type C
  • Registry

ASJC Scopus subject areas

  • Medicine(all)
  • Genetics(clinical)
  • Pharmacology (medical)

Cite this

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; Amado-Fondo, A.; Amraoui, Y.; Andria, G.; Arellano, M.; Audoin, B.; Azcona, C.; Barr, C.; Baruteau, J.; Baumgartner, C.; Bell, L.; Bembi, B.; Benneddif, K.; Bernard, G.; Bobocea, N.; Bodzioch, M.; Boettcher, T.; Bonnan, M.; Broue, P.; Bruni, A.; Caceres, M.; Camino, R.; Campbell, E.; Cances, C.; Cannell, P.; Cesar, J.; Chabrol, B.; Chakrapani, A.; Colao, R.; Collet, A.; Corsetti, T.; Cousins, A.; Covanis, A.; Cox, T.; Cuisset, J. M.; Dardis, A.; Das, A.; Deegan, P.; Dengler, T.; Deodato, F.; Derralynn, H.; Di Donato, I.; Di Rocco, M.; Uziel, G.; NPC Registry investigators.

In: Orphanet Journal of Rare Diseases, Vol. 10, No. 1, 65, 28.05.2015.

Research output: Contribution to journalArticle

Patterson, MC, Mengel, E, Vanier, MT, Schwierin, B, Muller, A, Cornelisse, P, Pineda, M, Amado-Fondo, A, Amraoui, Y, Andria, G, Arellano, M, Audoin, B, Azcona, C, Barr, C, Baruteau, J, Baumgartner, C, Bell, L, Bembi, B, Benneddif, K, Bernard, G, Bobocea, N, Bodzioch, M, Boettcher, T, Bonnan, M, Broue, P, Bruni, A, Caceres, M, Camino, R, Campbell, E, Cances, C, Cannell, P, Cesar, J, Chabrol, B, Chakrapani, A, Colao, R, Collet, A, Corsetti, T, Cousins, A, Covanis, A, Cox, T, Cuisset, JM, Dardis, A, Das, A, Deegan, P, Dengler, T, Deodato, F, Derralynn, H, Di Donato, I, Di Rocco, M, Uziel, G & NPC Registry investigators 2015, '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', Orphanet Journal of Rare Diseases, vol. 10, no. 1, 65. https://doi.org/10.1186/s13023-015-0284-z
Patterson, Marc C. ; Mengel, Eugen ; Vanier, Marie T. ; Schwierin, Barbara ; Muller, Audrey ; Cornelisse, Peter ; Pineda, Mercè ; Amado-Fondo, A. ; Amraoui, Y. ; Andria, G. ; Arellano, M. ; Audoin, B. ; Azcona, C. ; Barr, C. ; Baruteau, J. ; Baumgartner, C. ; Bell, L. ; Bembi, B. ; Benneddif, K. ; Bernard, G. ; Bobocea, N. ; Bodzioch, M. ; Boettcher, T. ; Bonnan, M. ; Broue, P. ; Bruni, A. ; Caceres, M. ; Camino, R. ; Campbell, E. ; Cances, C. ; Cannell, P. ; Cesar, J. ; Chabrol, B. ; Chakrapani, A. ; Colao, R. ; Collet, A. ; Corsetti, T. ; Cousins, A. ; Covanis, A. ; Cox, T. ; Cuisset, J. M. ; Dardis, A. ; Das, A. ; Deegan, P. ; Dengler, T. ; Deodato, F. ; Derralynn, H. ; Di Donato, I. ; Di Rocco, M. ; Uziel, G. ; NPC Registry investigators. / 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. In: Orphanet Journal of Rare Diseases. 2015 ; Vol. 10, No. 1.
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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 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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author = "Patterson, {Marc C.} and Eugen Mengel and Vanier, {Marie T.} and Barbara Schwierin and Audrey Muller and Peter Cornelisse and Merc{\~A}¨ Pineda and A. Amado-Fondo and Y. Amraoui and G. Andria and M. Arellano and B. Audoin and C. Azcona and C. Barr and J. Baruteau and C. Baumgartner and L. Bell and B. Bembi and K. Benneddif and G. Bernard and N. Bobocea and M. Bodzioch and T. Boettcher and M. Bonnan and P. Broue and A. Bruni and M. Caceres and R. Camino and E. Campbell and C. Cances and P. Cannell and J. Cesar and B. Chabrol and A. Chakrapani and R. Colao and A. Collet and T. Corsetti and A. Cousins and A. Covanis and T. Cox and Cuisset, {J. M.} and A. Dardis and A. Das and P. Deegan and T. Dengler and F. Deodato and H. Derralynn and {Di Donato}, I. and {Di Rocco}, M. and G. Uziel and {NPC Registry investigators}",
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TY - JOUR

T1 - Stable or improved neurological manifestations during miglustat therapy in patients from the international disease registry for Niemann-Pick disease type C

T2 - An observational cohort study

AU - Patterson, Marc C.

AU - Mengel, Eugen

AU - Vanier, Marie T.

AU - Schwierin, Barbara

AU - Muller, Audrey

AU - Cornelisse, Peter

AU - Pineda, Mercè

AU - Amado-Fondo, A.

AU - Amraoui, Y.

AU - Andria, G.

AU - Arellano, M.

AU - Audoin, B.

AU - Azcona, C.

AU - Barr, C.

AU - Baruteau, J.

AU - Baumgartner, C.

AU - Bell, L.

AU - Bembi, B.

AU - Benneddif, K.

AU - Bernard, G.

AU - Bobocea, N.

AU - Bodzioch, M.

AU - Boettcher, T.

AU - Bonnan, M.

AU - Broue, P.

AU - Bruni, A.

AU - Caceres, M.

AU - Camino, R.

AU - Campbell, E.

AU - Cances, C.

AU - Cannell, P.

AU - Cesar, J.

AU - Chabrol, B.

AU - Chakrapani, A.

AU - Colao, R.

AU - Collet, A.

AU - Corsetti, T.

AU - Cousins, A.

AU - Covanis, A.

AU - Cox, T.

AU - Cuisset, J. M.

AU - Dardis, A.

AU - Das, A.

AU - Deegan, P.

AU - Dengler, T.

AU - Deodato, F.

AU - Derralynn, H.

AU - Di Donato, I.

AU - Di Rocco, M.

AU - Uziel, G.

AU - NPC Registry investigators

PY - 2015/5/28

Y1 - 2015/5/28

N2 - 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.

AB - 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.

KW - Miglustat

KW - Niemann-Pick disease type C

KW - Registry

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