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Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study

This post-hoc analysis investigated the long-term effects of safinamide on the course of dyskinesia and efficacy outcomes using data from a phase III, open-label 52-week study of safinamide 50 or 100 mg/day in Japanese patients with Parkinson’s disease (PD) with wearing-off. Patients (N = 194) were...

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Autores principales: Hattori, Nobutaka, Kamei, Takanori, Ishida, Takayuki, Suzuki, Ippei, Nomoto, Masahiro, Tsuboi, Yoshio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Vienna 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468087/
https://www.ncbi.nlm.nih.gov/pubmed/36001147
http://dx.doi.org/10.1007/s00702-022-02532-2
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author Hattori, Nobutaka
Kamei, Takanori
Ishida, Takayuki
Suzuki, Ippei
Nomoto, Masahiro
Tsuboi, Yoshio
author_facet Hattori, Nobutaka
Kamei, Takanori
Ishida, Takayuki
Suzuki, Ippei
Nomoto, Masahiro
Tsuboi, Yoshio
author_sort Hattori, Nobutaka
collection PubMed
description This post-hoc analysis investigated the long-term effects of safinamide on the course of dyskinesia and efficacy outcomes using data from a phase III, open-label 52-week study of safinamide 50 or 100 mg/day in Japanese patients with Parkinson’s disease (PD) with wearing-off. Patients (N = 194) were grouped using the UPDRS Part IV item 32: with and without pre-existing dyskinesia (pre-D subgroup; item 32 > 0 at baseline [n = 81], without pre-D subgroup; item 32 = 0 at baseline [n = 113]). ON-time with troublesome dyskinesia (ON-TD) increased significantly from baseline to Week 4 in the pre-D subgroup (+ 0.25 ± 0.11 h [mean ± SE], p = 0.0355) but gradually decreased up to Week 52 (change from baseline: − 0.08 ± 0.17 h, p = 0.6224); ON-TD did not change significantly in the Without pre-D subgroup. UPDRS Part IV item 32 score increased significantly at Week 52 compared with baseline in the Without pre-D subgroup, but no UPDRS Part IV dyskinesia related-domains changed in the pre-D subgroup. Both subgroups improved in ON-time without TD, UPDRS Part III, and Part II [OFF-phase] scores. The cumulative incidence of new or worsening dyskinesia (adverse drug reaction) at Week 52 was 32.5 and 5.0% in the pre-D and Without pre-D subgroups, respectively. This study suggested that safinamide led to short-term increasing dyskinesia but may be not associated with marked dyskinesia at 1-year follow-up in patients with pre-existing dyskinesia, and that it improved motor symptoms regardless of the presence or absence of dyskinesia at baseline. Further studies are warranted to investigate this association in more details. Trial registration: JapicCTI-153057 (Registered: 2015/11/02). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00702-022-02532-2.
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spelling pubmed-94680872022-09-14 Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study Hattori, Nobutaka Kamei, Takanori Ishida, Takayuki Suzuki, Ippei Nomoto, Masahiro Tsuboi, Yoshio J Neural Transm (Vienna) Neurology and Preclinical Neurological Studies - Original Article This post-hoc analysis investigated the long-term effects of safinamide on the course of dyskinesia and efficacy outcomes using data from a phase III, open-label 52-week study of safinamide 50 or 100 mg/day in Japanese patients with Parkinson’s disease (PD) with wearing-off. Patients (N = 194) were grouped using the UPDRS Part IV item 32: with and without pre-existing dyskinesia (pre-D subgroup; item 32 > 0 at baseline [n = 81], without pre-D subgroup; item 32 = 0 at baseline [n = 113]). ON-time with troublesome dyskinesia (ON-TD) increased significantly from baseline to Week 4 in the pre-D subgroup (+ 0.25 ± 0.11 h [mean ± SE], p = 0.0355) but gradually decreased up to Week 52 (change from baseline: − 0.08 ± 0.17 h, p = 0.6224); ON-TD did not change significantly in the Without pre-D subgroup. UPDRS Part IV item 32 score increased significantly at Week 52 compared with baseline in the Without pre-D subgroup, but no UPDRS Part IV dyskinesia related-domains changed in the pre-D subgroup. Both subgroups improved in ON-time without TD, UPDRS Part III, and Part II [OFF-phase] scores. The cumulative incidence of new or worsening dyskinesia (adverse drug reaction) at Week 52 was 32.5 and 5.0% in the pre-D and Without pre-D subgroups, respectively. This study suggested that safinamide led to short-term increasing dyskinesia but may be not associated with marked dyskinesia at 1-year follow-up in patients with pre-existing dyskinesia, and that it improved motor symptoms regardless of the presence or absence of dyskinesia at baseline. Further studies are warranted to investigate this association in more details. Trial registration: JapicCTI-153057 (Registered: 2015/11/02). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00702-022-02532-2. Springer Vienna 2022-08-24 2022 /pmc/articles/PMC9468087/ /pubmed/36001147 http://dx.doi.org/10.1007/s00702-022-02532-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Neurology and Preclinical Neurological Studies - Original Article
Hattori, Nobutaka
Kamei, Takanori
Ishida, Takayuki
Suzuki, Ippei
Nomoto, Masahiro
Tsuboi, Yoshio
Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study
title Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study
title_full Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study
title_fullStr Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study
title_full_unstemmed Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study
title_short Long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in Parkinson’s disease: post-hoc analysis of a Japanese phase III study
title_sort long-term effects of safinamide adjunct therapy on levodopa-induced dyskinesia in parkinson’s disease: post-hoc analysis of a japanese phase iii study
topic Neurology and Preclinical Neurological Studies - Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9468087/
https://www.ncbi.nlm.nih.gov/pubmed/36001147
http://dx.doi.org/10.1007/s00702-022-02532-2
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