Efficacy of as-needed nalmefene in alcohol-dependent patients with at least a high drinking risk level: results from a subgroup analysis of two randomized controlled 6-month studies

Abstract

Aims: The aim of the study was to investigate the efficacy and safety of as-needed use of nalmefene 18 mg versus placebo in reducing alcohol consumption in patients who did not reduce their alcohol consumption after an initial assessment, i.e. the pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) at both screening and randomization from the two randomized controlled 6-month studies ESENSE 1 (NCT00811720) and ESENSE 2 (NCT00812461).

Methods: Nalmefene 18 mg and placebo were taken on an as-needed basis. All the patients also received a motivational and adherence-enhancing intervention (BRENDA). The co-primary outcomes were number of heavy drinking days (HDDs) and mean total alcohol consumption (g/day) in Month 6 measured using the Timeline Follow-back method. Additionally, data on clinical improvement, liver function and safety were collected throughout the study.

Results: The pooled population consisted of 667 patients: placebo n = 332; nalmefene n = 335. There was a superior effect of nalmefene compared with placebo in reducing the number of HDDs [treatment difference: -3.2 days (95% CI: -4.8; -1.6); P < 0.0001] and total alcohol consumption [treatment difference: -14.3 g/day (-20.8; -7.8); P < 0.0001] at Month 6. Improvements in clinical status and liver parameters were greater in the nalmefene group compared with the placebo group. Adverse events and adverse events leading to dropout were more common with nalmefene than placebo.

Conclusion: As-needed nalmefene was efficacious in reducing alcohol consumption in patients with at least a high drinking risk level at both screening and randomization, and the effect in this subgroup was larger than in the total population.

Fig. 1.

Flow chart of patient disposition. *Adverse events were not by default set to primary reason for dropout.

Fig. 2.

Monthly adjusted mean change from baseline in (A) heavy drinking days and (B) total alcohol consumption for patients with high drinking risk level at screening (i.e. baseline) and randomization from ESENSE 1 and ESENSE 2 pooled. Numbers below the x-axis indicate number of patients contributing with observations at each month. *P < 0.05 compared to placebo. Values are means ± the standard error (SE). B = baseline.

Fig. 3.

Change in clinical global impression-severity of illness. Adjusted mean change from baseline in Clinical Global Impression-Severity of Illness (CGI-S) scores for patients with at least a high drinking risk level at screening and randomization in (A) ESENSE 1 and (B) ESENSE 2. Values are means ± the standard error (SE). *P < 0.05 compared with placebo. B, baseline.

Fig. 4.

Change in clinical global impression-global improvement. Adjusted mean Clinical Global Impression-Global Improvement (CGI-I) scores for patients with at least a high drinking risk level at screening and randomization in (A) ESENSE 1 and (B) ESENSE 2. Values are means ± the standard error (SE). *P < 0.05 compared with placebo.