Efficacy and safety of leuprorelin acetate for subjects with spinal and bulbar muscular atrophy: pooled analyses of two randomized-controlled trials.
Adult
Aged
Antineoplastic Agents, Hormonal
/ therapeutic use
Bulbo-Spinal Atrophy, X-Linked
/ blood
Double-Blind Method
Female
Follow-Up Studies
Humans
Leuprolide
/ therapeutic use
Male
Middle Aged
Multicenter Studies as Topic
Randomized Controlled Trials as Topic
Testosterone
/ blood
Treatment Outcome
Clinical trial
Disease-modifying therapy
Leuprorelin acetate
Motor neuron disease
Spinal and bulbar muscular atrophy
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
May 2019
May 2019
Historique:
received:
14
10
2018
accepted:
16
02
2019
revised:
14
02
2019
pubmed:
9
3
2019
medline:
14
8
2019
entrez:
9
3
2019
Statut:
ppublish
Résumé
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied. Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began. The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, - 4.12% (95% CI, - 8.40-0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups. The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.
Sections du résumé
BACKGROUND
BACKGROUND
Spinal and bulbar muscular atrophy (SBMA) is an adult-onset, hereditary neuromuscular disease characterized by muscle atrophy, weakness, contraction fasciculation, and bulbar involvement. Although the causative gene, androgen receptor, has been identified, the development of novel therapeutics for SBMA is incomplete. In this study, the efficacy and safety of leuprorelin acetate administration for patients with SBMA, using the pooled data of two randomized-controlled trials, was studied.
METHODS
METHODS
Two randomized double-blinded studies (JASMITT-06DB and JASMITT-11DB) were done as multicentric, investigator-initiated clinical trials in Japan. In both studies, eligible patients were randomly assigned 1:1 to receive leuprorelin acetate administration once per 12 weeks for 48 weeks. The primary endpoint was the longitudinal change of pharyngeal barium residues from the baseline data measured with videofluorographic swallowing analyses. The pooled analysis plan was decided upon after the 06B study was finished and before the 11DB study began.
RESULTS
RESULTS
The primary endpoint difference between the leuprorelin group and the placebo group was pharyngeal barium residue after initial swallowing, - 4.12% (95% CI, - 8.40-0.15; p = 0.058). The primary endpoint of this study does not reach significant results, although inter-group differences of pharyngeal barium residues after the initial swallowing indicated that leuprorelin acetate may be effective at each assessment point in both study groups.
CONCLUSIONS
CONCLUSIONS
The efficacy of leuprorelin acetate for patients with SBMA was statistically similar in two randomized-controlled trials, and suggested that leuprorelin acetate may be effective and safe. Further investigations are needed to clarify the promising efficacy of the drug.
Identifiants
pubmed: 30847645
doi: 10.1007/s00415-019-09251-x
pii: 10.1007/s00415-019-09251-x
doi:
Substances chimiques
Antineoplastic Agents, Hormonal
0
Testosterone
3XMK78S47O
Leuprolide
EFY6W0M8TG
Types de publication
Journal Article
Langues
eng
Pagination
1211-1221Subventions
Organisme : Ministry of Health, Labour and Welfare
ID : CCT-A-1603
Organisme : Ministry of Health, Labour and Welfare
ID : CCT-B-1701
Organisme : Ministry of Health, Labour and Welfare
ID : CCT-C-1810
Organisme : Ministry of Health, Labour and Welfare
ID : CCT-C-2340
Investigateurs
H Sasaki
(H)
M Aoki
(M)
I Nakano
(I)
S Ito
(S)
H Mizusawa
(H)
To Yamamoto
(T)
K Hasegawa
(K)
H Miyajima
(H)
G Sobue
(G)
N Kanda
(N)
K Nakajima
(K)
A Tsujino
(A)
M Uchino
(M)
M Morita
(M)
K Kanai
(K)
Ta Yamamoto
(T)
H Mizusawa
(H)
To Yamamoto
(T)
G Sobue
(G)
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