Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies.

Jonathan Chick,Kathrin Borchert,Jennifer S Haas,Elin Heldbo Reines,Kavitha Kuppan,Ole M Lemming,Sebastian Braun,Florence Tubach,Massoud Toussi,Sylvie Guillo,Frank Andersohn

doi:10.1093/alcalc/agab045

Abstract

AimsTwo post-authorisation studies assessed the safety and persistence of patients’ use of nalmefene.MethodsThe START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted ‘all comers’ without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities.ResultsSTART study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were ‘goal reached’ and ‘drug cost’. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year.ConclusionsDespite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.

Highlights

Alcohol dependence is a common medical and behavioural disorder with a high probability of a chronic relapsing and progressive course
Few patients took more than the recommended dose of one tablet per day, and there were fewer recorded instances of possible ‘overdosing’ (i.e. >1 tablet per day) in Germany and Sweden than in the UK (6.1% and 0.9% vs. 16.5%, respectively). Results from these routine practice studies provide valuable safety data in important subpopulations of patients who were not the main population studied in the previous pivotal studies (Gual et al, 2013; Mann et al, 2013; van den Brink et al, 2014; Miyata et al, 2019) and confirm the favourable benefit–risk profile of nalmefene treatment in the wider alcohol-dependent population
Results show no major differences in safety outcomes between the total population, and those with psychiatric and somatic comorbidities or a history of seizures, except a slightly greater prevalence of adverse drug reactions (ADRs) in the elderly

Summary

Introduction

Alcohol dependence is a common medical and behavioural disorder with a high probability of a chronic relapsing and progressive course. European approval of nalmefene was based on the results of a package of phase III clinical trials which consistently demonstrated that nalmefene, given on an as-needed basis and together with psychosocial support, significantly reduces the total amount of alcohol consumption and number of heavy drinking days in people with alcohol dependence (Gual et al, 2013; Mann et al, 2013; van den Brink et al, 2013; van den Brink et al, 2014; Miyata et al, 2019). Limited study sample sizes and duration of follow up do not allow the identification of potential rare adverse events or long term off-label use

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Results

Conclusion