TY - JOUR
T1 - Clinical moderators of response to nalmefene in a randomized-controlled trial for alcohol dependence
T2 - An exploratory analysis
AU - Hashimoto, Nozomu
AU - Habu, Hiroshi
AU - Takao, Soshi
AU - Sakamoto, Shinji
AU - Okahisa, Yuko
AU - Matsuo, Keitaro
AU - Takaki, Manabu
AU - Kishi, Yoshiki
AU - Yamada, Norihito
N1 - Funding Information:
N.H. has received honoraria for his participation as a speaker at educational events sponsored by Otsuka. S.S. has received unrestricted research funding from Eli Lilly, which was deposited into research accounts at Okayama University Hospital. S.S. has received honoraria for his participation as a speaker at an educational event sponsored by Otsuka and Meiji-Seika. M.T. has received honoraria for his participation as a speaker at educational events sponsored by Otsuka, Dainippon Sumitomo, and Takeda. N.Y. has received unrestricted research funding from Daiichi Sankyo, Eisai, Pfizer, Otsuka, Astellas, and Merck Sharp & Dohme, which was deposited into research accounts at Okayama University. N.Y. has received honoraria for his participation as a speaker at educational events from UCB Japan, Tsumura, Pfizer, Dainippon-Sumitomo, Daiichi-Sankyo, Merck Sharp & Dohme, Pfizer, Eisai, Meiji-Seika, and Mochida. H.H., S.T., Y.O., K.M., Y.K. report no additional financial or other relationship relevant to this article.
Funding Information:
The authors would like to thank the Zikei Institute of Psychiatry (Okayama, Japan). This publication is based on research using data from data contributor ?Otsuka Pharmaceuticals? that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication. N.H. has received honoraria for his participation as a speaker at educational events sponsored by Otsuka. S.S. has received unrestricted research funding from Eli Lilly, which was deposited into research accounts at Okayama University Hospital. S.S. has received honoraria for his participation as a speaker at an educational event sponsored by Otsuka and Meiji-Seika. M.T. has received honoraria for his participation as a speaker at educational events sponsored by Otsuka, Dainippon Sumitomo, and Takeda. N.Y. has received unrestricted research funding from Daiichi Sankyo, Eisai, Pfizer, Otsuka, Astellas, and Merck Sharp & Dohme, which was deposited into research accounts at Okayama University. N.Y. has received honoraria for his participation as a speaker at educational events from UCB Japan, Tsumura, Pfizer, Dainippon-Sumitomo, Daiichi-Sankyo, Merck Sharp & Dohme, Pfizer, Eisai, Meiji-Seika, and Mochida. H.H. S.T. Y.O. K.M. Y.K. report no additional financial or other relationship relevant to this article.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - Background: Nalmefene is the only medication marketed to reduce the consumption of alcohol in patients with alcohol dependence, but it remains unclear which patients could most benefit from it. This study aimed to identify clinical moderators that affect treatment response to nalmefene in patients with alcohol dependence. Methods: In a multicenter, randomized, controlled, double-blind, phase 3 study of nalmefene on Japanese patients with alcohol dependence, the relationship between the reduction of heavy drinking days (HDD) and total alcohol consumption (TAC) at 12 and 24 weeks of treatment and baseline variables of the participants were analyzed in a linear regression and multiple adjusted analysis. Results: Age < 65, no family history of problem drinking, age at onset of problem drinking ≥ 25, and not currently smoking were possible positive moderators. Nalmefene showed a significant HDD reduction in patients with age < 65 or no family history of problem drinking, and a significant TAC reduction in patients with age at onset of problem drinking ≥ 25 or who were not currently smoking. After multiple adjusted analyses, age < 65 (p =.028), no family history of problem drinking (p =.047), and age at onset of problem drinking ≥ 25 (p =.030) were statistically significant. Not currently smoking (p =.071) was marginally significant. In combination, these moderators indicated synergistic effects. Conclusions: Alcohol-dependent patients with favorable prognostic factors such as non-smoking status, no family history of problem drinking, and a late-onset of problem drinking selectively benefit from nalmefene. Further research is needed to validate these exploratory results.
AB - Background: Nalmefene is the only medication marketed to reduce the consumption of alcohol in patients with alcohol dependence, but it remains unclear which patients could most benefit from it. This study aimed to identify clinical moderators that affect treatment response to nalmefene in patients with alcohol dependence. Methods: In a multicenter, randomized, controlled, double-blind, phase 3 study of nalmefene on Japanese patients with alcohol dependence, the relationship between the reduction of heavy drinking days (HDD) and total alcohol consumption (TAC) at 12 and 24 weeks of treatment and baseline variables of the participants were analyzed in a linear regression and multiple adjusted analysis. Results: Age < 65, no family history of problem drinking, age at onset of problem drinking ≥ 25, and not currently smoking were possible positive moderators. Nalmefene showed a significant HDD reduction in patients with age < 65 or no family history of problem drinking, and a significant TAC reduction in patients with age at onset of problem drinking ≥ 25 or who were not currently smoking. After multiple adjusted analyses, age < 65 (p =.028), no family history of problem drinking (p =.047), and age at onset of problem drinking ≥ 25 (p =.030) were statistically significant. Not currently smoking (p =.071) was marginally significant. In combination, these moderators indicated synergistic effects. Conclusions: Alcohol-dependent patients with favorable prognostic factors such as non-smoking status, no family history of problem drinking, and a late-onset of problem drinking selectively benefit from nalmefene. Further research is needed to validate these exploratory results.
KW - Alcohol dependence
KW - Alcohol use disorder
KW - Clinical moderators
KW - Kappa opioid receptors
KW - Nalmefene
KW - Naltrexone
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U2 - 10.1016/j.drugalcdep.2022.109365
DO - 10.1016/j.drugalcdep.2022.109365
M3 - Article
C2 - 35228081
AN - SCOPUS:85125250347
SN - 0376-8716
VL - 233
JO - Drug and Alcohol Dependence
JF - Drug and Alcohol Dependence
M1 - 109365
ER -
