Therapeutic impact of leuprorelin acetate on spinal and bulbar muscular atrophy : pre- and post-marketing observational study
(2025) In Journal of Neurology 272(12).- Abstract
Although leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, has been approved based on short-term clinical trials conducted in Japan, its long-term efficacy on physical function remains unclear. We aimed to evaluate the long-term therapeutic efficacy of leuprorelin acetate using real-world clinical data through a self-controlled trend-shift analysis. The analysis included 91 genetically confirmed patients with spinal and bulbar muscular atrophy, with follow-up data collected before and after treatment initiation. The functional outcomes assessed included the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and modified Norris scales, grip power, and serum creatinine levels. Leuprorelin acetate... (More)
Although leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, has been approved based on short-term clinical trials conducted in Japan, its long-term efficacy on physical function remains unclear. We aimed to evaluate the long-term therapeutic efficacy of leuprorelin acetate using real-world clinical data through a self-controlled trend-shift analysis. The analysis included 91 genetically confirmed patients with spinal and bulbar muscular atrophy, with follow-up data collected before and after treatment initiation. The functional outcomes assessed included the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and modified Norris scales, grip power, and serum creatinine levels. Leuprorelin acetate significantly slowed disease progression. For instance, the annual ALSFRS-R decline rate improved from approximately 0.5 points pre-treatment to 0.2 points post-treatment. The subgroup analysis supported the potential benefit of early intervention. These findings highlight the value of leveraging patient registries and post-marketing real-world data to evaluate treatment efficacy in slowly progressive diseases, such as SBMA, where traditional randomized controlled trials are often limited by insufficient statistical power to detect therapeutic efficacy. They also underscore the need for innovative methodologies to assess post-approval drug performance, paving the way for improved clinical outcomes for neurodegenerative diseases.
(Less)
- author
- Hashizume, Atsushi
; Hanazawa, Ryoichi
; Yamada, Shinichiro
; Ito, Daisuke
LU
; Kishimoto, Yoshiyuki
; Komori, Shota
; Kawase, Takahiro
; Iida, Madoka
; Kondo, Ayano
; Mori, Yu
; Obara, Kazuki
LU
; Morita, Mitsuya
; Yamamoto, Tomotaka
; Sato, Hiroyuki
; Hirakawa, Akihiro
and Katsuno, Masahisa
LU
(Less) - publishing date
- 2025-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Leuprorelin acetate, Random coefficient linear regression model, Real-world data, Spinal and bulbar muscular atrophy, Trend shift analysis
- in
- Journal of Neurology
- volume
- 272
- issue
- 12
- article number
- 772
- publisher
- Springer
- external identifiers
-
- pmid:41258507
- scopus:105022229802
- ISSN
- 0340-5354
- DOI
- 10.1007/s00415-025-13509-y
- language
- English
- LU publication?
- no
- additional info
- Publisher Copyright: © Springer-Verlag GmbH Germany, part of Springer Nature 2025.
- id
- f143b55f-8755-440b-b12c-5d265b7dab33
- date added to LUP
- 2025-12-22 14:50:38
- date last changed
- 2025-12-23 03:49:55
@article{f143b55f-8755-440b-b12c-5d265b7dab33,
abstract = {{<p>Although leuprorelin acetate, a luteinizing hormone-releasing hormone agonist, has been approved based on short-term clinical trials conducted in Japan, its long-term efficacy on physical function remains unclear. We aimed to evaluate the long-term therapeutic efficacy of leuprorelin acetate using real-world clinical data through a self-controlled trend-shift analysis. The analysis included 91 genetically confirmed patients with spinal and bulbar muscular atrophy, with follow-up data collected before and after treatment initiation. The functional outcomes assessed included the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) and modified Norris scales, grip power, and serum creatinine levels. Leuprorelin acetate significantly slowed disease progression. For instance, the annual ALSFRS-R decline rate improved from approximately 0.5 points pre-treatment to 0.2 points post-treatment. The subgroup analysis supported the potential benefit of early intervention. These findings highlight the value of leveraging patient registries and post-marketing real-world data to evaluate treatment efficacy in slowly progressive diseases, such as SBMA, where traditional randomized controlled trials are often limited by insufficient statistical power to detect therapeutic efficacy. They also underscore the need for innovative methodologies to assess post-approval drug performance, paving the way for improved clinical outcomes for neurodegenerative diseases.</p>}},
author = {{Hashizume, Atsushi and Hanazawa, Ryoichi and Yamada, Shinichiro and Ito, Daisuke and Kishimoto, Yoshiyuki and Komori, Shota and Kawase, Takahiro and Iida, Madoka and Kondo, Ayano and Mori, Yu and Obara, Kazuki and Morita, Mitsuya and Yamamoto, Tomotaka and Sato, Hiroyuki and Hirakawa, Akihiro and Katsuno, Masahisa}},
issn = {{0340-5354}},
keywords = {{Leuprorelin acetate; Random coefficient linear regression model; Real-world data; Spinal and bulbar muscular atrophy; Trend shift analysis}},
language = {{eng}},
number = {{12}},
publisher = {{Springer}},
series = {{Journal of Neurology}},
title = {{Therapeutic impact of leuprorelin acetate on spinal and bulbar muscular atrophy : pre- and post-marketing observational study}},
url = {{http://dx.doi.org/10.1007/s00415-025-13509-y}},
doi = {{10.1007/s00415-025-13509-y}},
volume = {{272}},
year = {{2025}},
}