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Aim: We assessed relative efficacy and safety of amivantamab versus mobocertinib in patients with non-small-cell lung cancer with EGFR exon 20 insertion (exon20ins) mutations who progressed on prior platinum-based chemotherapy. Materials & methods: This matching-adjusted indirect comparison used patient-level data from CHRYSALIS (NCT02609776) and aggregate data from a mobocertinib trial (NCT02716116) to match populations on all clinically relevant confounders. Results: While both agents had similar efficacy for time-to-event outcomes, objective response rate was significantly higher for amivantamab. 15 of 23 any-grade treatment-related adverse events reported for mobocertinib were significantly less common for amivantamab versus only two for mobocertinib. Conclusion: Results suggest that amivantamab has an improved response rate with similar survival and a more favorable safety profile versus mobocertinib in EGFR exon20ins non-small-cell lung cancer.
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Compuestos de Anilina , Anticuerpos Biespecíficos , Carcinoma de Pulmón de Células no Pequeñas , Indoles , Neoplasias Pulmonares , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Receptores ErbB/genética , Exones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Mutación , Platino (Metal) , Inhibidores de Proteínas Quinasas/efectos adversosRESUMEN
This study explores sociocultural differences in alcohol-related impact on quality of life between France and United Kingdom. We included 38 alcohol-dependent patients in France and United Kingdom in 10 focus groups. We used a text-mining approach. Three classes of each corpus regarded identical themes across the countries: (a) core impact on quality of life, (b) drinking habits, (c) sources of help. Core impact was similar between the two countries. Main differences were in drinking habits and referral to sources of help. Despite differences in drinking habits, the domains of life impacted by alcohol were non-country specific.
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Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/epidemiología , Comparación Transcultural , Calidad de Vida , Adulto , Anciano , Minería de Datos , Femenino , Grupos Focales , Francia , Humanos , Masculino , Persona de Mediana Edad , Reino Unido , Adulto JovenRESUMEN
AIMS: To characterize a contemporaneous cohort of UK general practice patients with alcohol use disorder and describe their management. METHODS: Prospective observational study in 25 primary care practices in England and Scotland. Adult patients with known or suspected alcohol dependence (Alcohol Use Disorders Identification Test score ≥8) were followed for 6 months and were profiled using baseline data. Changes over time in treatment for alcohol dependence (strategy, goals, modality) and the level of compliance were examined. RESULTS: Targeted case identification was a feasible means of identifying patients with DSM-IV confirmed alcohol dependence in general practice. In the cohort (n = 218), mean total alcohol consumption was high (men: 86.9 g/day; women: 62.7 g/day) and psychiatric co-morbidities were common (depression: 25.8% of patients; anxiety disorders: 25.8% of patients). At baseline, about half of patients reported ongoing or planned treatment for alcohol dependence. Over 6 months' observation, treatment modalities did not change and most patients retained their original stated treatment goal of abstinence or reduced alcohol intake. CONCLUSIONS: Targeted case identification in general practice identifies patients with alcohol use disorder in need of treatment.
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Trastornos Relacionados con Alcohol/terapia , Medicina General/métodos , Pautas de la Práctica en Medicina , Adolescente , Adulto , Anciano , Trastornos Relacionados con Alcohol/complicaciones , Femenino , Medicina General/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Pautas de la Práctica en Medicina/estadística & datos numéricos , Estudios Prospectivos , Reino Unido , Adulto JovenRESUMEN
BACKGROUND: Most available pharmacotherapies for alcohol-dependent patients target abstinence; however, reduced alcohol consumption may be a more realistic goal. Using randomized clinical trial (RCT) data, a previous microsimulation model evaluated the clinical relevance of reduced consumption in terms of avoided alcohol-attributable events. Using real-life observational data, the current analysis aimed to adapt the model and confirm previous findings about the clinical relevance of reduced alcohol consumption. METHODS: Based on the prospective observational CONTROL study, evaluating daily alcohol consumption among alcohol-dependent patients, the model predicted the probability of drinking any alcohol during a given day. Predicted daily alcohol consumption was simulated in a hypothetical sample of 200,000 patients observed over a year. Individual total alcohol consumption (TAC) and number of heavy drinking days (HDD) were derived. Using published risk equations, probabilities of alcohol-attributable adverse health events (e.g., hospitalizations or death) corresponding to simulated consumptions were computed, and aggregated for categories of patients defined by HDDs and TAC (expressed per 100,000 patient-years). Sensitivity analyses tested model robustness. RESULTS: Shifting from >220 HDDs per year to 120-140 HDDs and shifting from 36,000-39,000 g TAC per year (120-130 g/day) to 15,000-18,000 g TAC per year (50-60 g/day) impacted substantially on the incidence of events (14,588 and 6148 events avoided per 100,000 patient-years, respectively). Results were robust to sensitivity analyses. CONCLUSIONS: This study corroborates the previous microsimulation modeling approach and, using real-life data, confirms RCT-based findings that reduced alcohol consumption is a relevant objective for consideration in alcohol dependence management to improve public health.
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Consumo de Bebidas Alcohólicas/epidemiología , Alcoholismo/epidemiología , Adulto , Abstinencia de Alcohol/estadística & datos numéricos , Simulación por Computador , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Estudios Prospectivos , Salud PúblicaRESUMEN
AIMS: In patients with alcohol dependence, health-related quality of life (QOL) is reduced compared with that of a normal healthy population. The objective of the current analysis was to describe the evolution of health-related QOL in adults with alcohol dependence during a 24-month period after initial assessment for alcohol-related treatment in a routine practice setting, and its relation to drinking pattern which was evaluated across clusters based on the predominant pattern of alcohol use, set against the influence of baseline variables METHODS: The Medical Outcomes Study 36-Item Short-Form Survey (MOS-SF-36) was used to measure QOL at baseline and quarterly for 2 years among participants in CONTROL, a prospective observational study of patients initiating treatment for alcohol dependence. The sample consisted of 160 adults with alcohol dependence (65.6% males) with a mean (SD) age of 45.6 (12.0) years. Alcohol use data were collected using TimeLine Follow-Back. Based on the participant's reported alcohol use, three clusters were identified: 52 (32.5%) mostly abstainers, 64 (40.0%) mostly moderate drinkers and 44 (27.5%) mostly heavy drinkers. Mixed-effect linear regression analysis was used to identify factors that were potentially associated with the mental and physical summary MOS-SF-36 scores at each time point. RESULTS: The mean (SD) MOS-SF-36 mental component summary score (range 0-100, norm 50) was 35.7 (13.6) at baseline [mostly abstainers: 40.4 (14.6); mostly moderate drinkers 35.6 (12.4); mostly heavy drinkers 30.1 (12.1)]. The score improved to 43.1 (13.4) at 3 months [mostly abstainers: 47.4 (12.3); mostly moderate drinkers 44.2 (12.7); mostly heavy drinkers 35.1 (12.9)], to 47.3 (11.4) at 12 months [mostly abstainers: 51.7 (9.7); mostly moderate drinkers 44.8 (11.9); mostly heavy drinkers 44.1 (11.3)], and to 46.6 (11.1) at 24 months [mostly abstainers: 49.2 (11.6); mostly moderate drinkers 45.7 (11.9); mostly heavy drinkers 43.7 (8.8)]. Mixed-effect linear regression multivariate analyses indicated that there was a significant association between a lower 2-year follow-up MOS-SF-36 mental score and being a mostly heavy drinker (-6.97, P < 0.001) or mostly moderate drinker (-3.34 points, P = 0.018) [compared to mostly abstainers], being female (-3.73, P = 0.004), and having a Beck Inventory scale score ≥8 (-6.54, P < 0.001), at baseline. The mean (SD) MOS-SF-36 physical component summary score was 48.8 (10.6) at baseline, remained stable over the follow-up and did not differ across the three clusters. Mixed-effect linear regression univariate analyses found that the average 2-year follow-up MOS-SF-36 physical score was increased (compared with mostly abstainers) in mostly heavy drinkers (+4.44, P = 0.007); no other variables tested influenced the MOS-SF-36 physical score. CONCLUSION: Among individuals with alcohol dependence, a rapid improvement was seen in the mental dimension of QOL following treatment initiation, which was maintained during 24 months. Improvement was associated with the pattern of alcohol use, becoming close to the general population norm in patients classified as mostly abstainers, improving substantially in mostly moderate drinkers and improving only slightly in mostly heavy drinkers. The physical dimension of QOL was generally in the normal range but was not associated with drinking patterns.
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Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/psicología , Calidad de Vida/psicología , Adulto , Femenino , Estado de Salud , Encuestas Epidemiológicas/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Análisis de RegresiónRESUMEN
BACKGROUND: Alcohol consumption is one of the most important factors for disease and disability in Europe. In clinical trials, nalmefene has resulted in a significant reduction in the number of heavy-drinking days (HDDs) per month and total alcohol consumption (TAC) among alcohol-dependent patients versus placebo. METHODS: A microsimulation model was developed to estimate alcohol-attributable diseases and injuries in patients with alcohol dependence and to explore the clinical relevance of reducing alcohol consumption. RESULTS: For all diseases and injuries considered, the number of events (inpatient episodes) increased with the number of HDDs and TAC per year. The model predicted that a reduction of 20 HDDs per year would result in 941 fewer alcohol-attributable events per 100,000 patients, while a reduction in intake of 3,000 g/year of pure alcohol (ethanol) would result in 1,325 fewer events per 100,000 patients. CONCLUSION: The potential gains of reducing consumption in alcohol-dependent patients were considerable.
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Consumo de Bebidas Alcohólicas/prevención & control , Trastornos Relacionados con Alcohol/prevención & control , Alcoholismo/rehabilitación , Reducción del Daño , Naltrexona/análogos & derivados , Antagonistas de Narcóticos/uso terapéutico , Heridas y Lesiones/prevención & control , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Trastornos Relacionados con Alcohol/etiología , Alcoholismo/complicaciones , Simulación por Computador , Inglaterra , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Modelos Teóricos , Naltrexona/uso terapéutico , Heridas y Lesiones/etiologíaRESUMEN
BACKGROUND: Amivantamab, an EGFR-MET bispecific antibody, is the first approved targeted therapy for patients with EGFR Ex20ins NSCLC after prior platinum-based chemotherapy-a population with historically poor outcomes before amivantamab approval. As antitumor activity in single-arm studies typically focuses on responders, the evaluation of outcomes in patients with stable disease (SD) as best response is of clinical interest. PATIENTS AND METHODS: Among 114 patients with post-platinum EGFR Ex20ins NSCLC in CHRYSALIS (NCT02609776; data cutoff: March 30, 2021), response was assessed by blinded independent central review via RECIST v1.1. Patients alive and receiving therapy at 12 weeks were grouped by response at this landmark: partial or complete response (PR+), SD, or progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) by response cohort were determined using the Kaplan-Meier method; hazard ratios (HRs) and 95% confidence intervals (CIs) between response cohorts were calculated using Cox proportional hazards regression. RESULTS: Among patients alive and receiving therapy at 12 weeks (n=107), 42 (39%) had PR+, 52 (49%) had SD, and 13 (12%) had PD. Among patients with PR+ and SD, median PFS was 12.2 and 7.0 months, respectively. A corresponding improvement in OS was observed in patients achieving PR+ (median: not reached; HR vs PD=0.21 [95% CI: 0.08-0.54]) and SD (median: 23.0 months; HR vs PD=0.33 [95% CI: 0.14-0.77]), relative to those with PD (median: 14.0 months). CONCLUSION: SD was observed in 49% of patients receiving amivantamab, with corresponding increases in OS that dramatically improved the prognoses of this patient population.
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Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data.
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INTRODUCTION: Patients with advanced, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) with Exon 20 insertion mutations (Exon20ins) have poor prognoses, exacerbated by a previous lack of specific treatment guidelines and unmet need for targeted therapies. Amivantamab, an EGFR and MET bispecific antibody, demonstrated efficacy and tolerability in patients with advanced EGFR-mutated NSCLC with Exon20ins following platinum-based therapy in CHRYSALIS (NCT02609776; Cohort D+). Since CHRYSALIS was single-arm, individual patient data (IPD)-based adjusted analyses versus similar patients in real-world clinical practice (RWCP) were conducted to generate comparative evidence. METHODS: RWCP cohorts were derived from seven European and US real-world sources, comprising patients fulfilling CHRYSALIS Cohort D+ eligibility criteria. Amivantamab was compared with a basket of RWCP treatments. Differences in prognostic characteristics were adjusted for using inverse probability weighting (IPW; average treatment effect among the treated [ATT]). Balance between cohorts was assessed using standardized mean differences (SMDs). Overall response rate (ORR; investigator- [INV] and independent review committee-assessed [IRC]), overall survival (OS), progression-free survival (PFS; INV and IRC) and time-to-next treatment (TTNT) were compared. Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively. RESULTS: Pre-adjustment, baseline characteristics were comparable between cohorts. IPW ATT-adjustment improved comparability, giving closely matched characteristics. ORR (INV) was 36.8% for amivantamab versus 17.0% for the adjusted EU + US cohort (response rate ratio [RR]: 2.16). Median OS, PFS (INV) and TTNT were 22.77 versus 12.52 months (hazard ratio [HR]: 0.47; p < 0.0001), 6.93 versus 4.17 months (HR: 0.55; p < 0.0001) and 12.42 versus 5.36 months (HR: 0.44; p < 0.0001) for amivantamab versus the adjusted EU + US cohort, respectively. Results were consistent versus EU- and US-only cohorts, and when using IRC assessment. CONCLUSION: Adjusted comparisons demonstrated significantly improved outcomes for amivantamab versus RWCP, highlighting the value of amivantamab in addressing unmet need in patients with advanced EGFR Exon20ins NSCLC following platinum-based therapy. TRIAL REGISTRATION: CHRYSALIS: NCT02609776.
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Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Estados Unidos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Antineoplásicos/uso terapéutico , Mutagénesis Insercional , Receptores ErbB/genética , Receptores ErbB/uso terapéutico , Mutación , Inhibidores de Proteínas Quinasas/uso terapéuticoRESUMEN
CONTEXT AND OBJECTIVE: The objective of assessing "quality of life" is to take better consideration of the patients' perception of their own state of health by developing specific measurement tools. Paradoxically, there is no questionnaire evaluating the impact of such treatment on women's quality of life. There was, therefore, a need for the creation of the CosmeceutiQoL. METHOD: The questionnaire was developed using methodology in accordance with international standards in terms of quality of life. RESULTS: The score of the CosmeceutiQoL was correlated to age. The more sensitive the skin is, the lower is the quality of life. For women who declared that their facial skin had started to sag, the quality of life was significantly lower. Deterioration of quality of life was also significantly observed in women who declared that they had age spots on the skin of their face and in women who said that their facial skin was dehydrated. We observed an altered CosmeceutiQoL score in women who declared that they had wrinkles, sagging skin or dark or brown spot. DISCUSSION: The CosmeceutiQoL scale which is essentially based on the women's point of view, is a valid, pertinent, and well accepted tool enabling the assessment of quality of life perceived through the skin. The more CosmeceutiQoL is altered, the more intense the signs of aging on the face, wrinkles, skin sagging, or dark or brown spots are observed, irrespective of the age.
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Calidad de Vida , Envejecimiento de la Piel , Encuestas y Cuestionarios , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Modelos Lineales , Persona de Mediana Edad , Trastornos de la Pigmentación/psicología , Análisis de Componente Principal , Fenómenos Fisiológicos de la PielRESUMEN
BACKGROUND: Information on the epidemiology of uncommon EGFR mutations including exon 20 insertions amongst non-small-cell lung cancer (NSCLC) is lacking. OBJECTIVE: The objective of this pragmatic literature review (PLR) and meta-analysis was to generate robust prevalence and incidence estimates based on ranges of exon 20 insertion mutations reported in the literature. MATERIALS AND METHODS: Searches of MEDLINE, Embase, congresses and reference lists for articles published from 2013 in key European countries of interest (Belgium, France, Germany, Italy, The Netherlands, Spain, Sweden, Switzerland, United Kingdom) were performed. Articles were reviewed against pre-specified criteria and their quality was appraised using a published checklist. Prevalence estimates were synthesised by random-effects meta-analyses. RESULTS: Eighty unique studies of moderate-to-high quality were included in the PLR. The meta-analysed prevalence for EGFR mutations was 12.5% (95% confidence interval [CI]: 11.0, 14.1) in any stage NSCLC and 14.8% (12.8, 17.1) in advanced/metastatic NSCLC. The prevalence of exon 20 insertions was 0.7% (0.4, 1.1) in any stage NSCLC and 6.1% (4.0, 9.4) in any stage EGFR-positive NSCLC. Mutation status was primarily measured using direct sequencing or a combination of methods. One study reporting exon 20 insertions in advanced/metastatic disease was identified, which reported a prevalence of 0.5% in overall NSCLC and 4.0% in EGFR-positive NSCLC. CONCLUSIONS: EGFR exon 20 insertion mutations are rare in NSCLC. There is a high unmet need in patients with exon 20 insertions, including effective therapies. Prospective cohort studies are needed to better clinically characterise these patients.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Receptores ErbB/genética , Exones , Humanos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Mutagénesis Insercional , Mutación , Prevalencia , Estudios Prospectivos , Inhibidores de Proteínas QuinasasRESUMEN
BACKGROUND: Hand-foot syndrome (HFS) is a common reaction to certain chemotherapies and new targeted therapies, impairing patient quality of life (QoL). However, there is currently no specific tool to measure QoL in patients with HFS. Objective. The objective was to develop and validate a HFS-specific QoL questionnaire (HFS-14). PATIENTS AND METHODS: From a list of 31 items identified from a literature review and patient interview notes, item reduction and pilot testing by cognitive debriefing resulted in a final 14-item questionnaire with excellent internal reliability. Clinical validity was assessed in 43 patients with HFS by comparing the HFS-14 score according to HFS clinical grade based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 3.0, and by measuring its correlation with the Dermatology Life Quality Index (DLQI), Skindex-16, and short-form 12 health-related questionnaires and pain measurement. RESULTS: The mean HFS-14 score was significantly higher in patients with clinical grade 2 and grade 3 HFS than in those with grade 1 HFS. The higher the HFS-14 score, the greater the QoL impairment. The HFS-14 score was highly correlated with the DLQI and Skindex-16 scores. In the population of patients with severe grade 3 NCI-CTCAE HFS, the HFS-14 score was significantly higher in patients having both hands and feet severely involved than in those with severe involvement of one limb (hands or feet) with the other one less severely affected. CONCLUSIONS: This scale specifically developed for patients with HFS is a valid and valuable tool for measuring HFS-related QoL impairment.
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Síndrome Mano-Pie/patología , Síndrome Mano-Pie/psicología , Calidad de Vida , Encuestas y Cuestionarios/normas , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: A microsimulation model was adapted to evaluate the cost-effectiveness of nalmefene combined with psychosocial support (NMF + PS) versus psychosocial support alone (PS). The economic impact of alcohol reduction using nalmefene treatment was not evaluated. METHOD: The model simulates patient-level alcohol consumption over a 5-year time horizon across different treatment cohorts. Study outcomes included probabilities of alcohol-attributable diseases and injuries as well as deaths from these events. The approach used nalmefene clinical trial data, a time horizon of 1 and 5 years, and a U.K. societal perspective. Extensive deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Compared with the PS strategy, NMF + PS was associated at Year 5 with a gain of 0.047 quality-adjusted life years (QALYs) and an additional £503, leading to an incremental cost-effectiveness ratio (ICER) of £10,613 per QALY gained. When compared with the strategy without treatment, NMF + PS was associated with a gain of 0.228 QALYs and an additional £1,795, leading to an ICER of £1,758 per QALY gained. The NMF + PS strategy dominated both treatment strategies when considering the U.K. societal perspective. Sensitivity analyses confirmed the robustness of the results. CONCLUSIONS: A combination of NMF and PS was better than PS alone, considering a 5-year time horizon and a societal perspective.
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Consumo de Bebidas Alcohólicas/prevención & control , Alcoholismo/terapia , Naltrexona/análogos & derivados , Años de Vida Ajustados por Calidad de Vida , Consumo de Bebidas Alcohólicas/economía , Análisis Costo-Beneficio , Femenino , Humanos , Masculino , Persona de Mediana Edad , Naltrexona/administración & dosificación , RiesgoRESUMEN
BACKGROUND: Alcohol dependence causes considerable harm to patients. Treatment with nalmefene, aiming to reduce consumption rather than maintain complete abstinence, has been licensed based on trials demonstrating a reduction in total alcohol consumption and heavy drinking days. Relating these trial outcomes to harmful events avoided is important to demonstrate the clinical relevance of nalmefene treatment. METHODS: A predictive microsimulation model was developed to compare nalmefene plus brief psychosocial intervention (BRENDA) versus placebo plus BRENDA for the treatment of patients with alcohol dependence and a high or very high drinking risk level based on three pooled clinical trials. The model simulated patterns and level of alcohol consumption, day-by-day, for 12 months, to estimate the occurrence of alcohol-attributable diseases, injuries and deaths; assessing the clinical relevance of reducing alcohol consumption with treatment. RESULTS: The microsimulation model predicted that, in a cohort of 100,000 patients, 971 (95 % confidence interval [CI] 904-1038) alcohol-attributable diseases and injuries and 133 (95 % CI 117-150) deaths would be avoided with nalmefene versus placebo. This level of benefit has been considered clinically relevant by the European Medicines Agency. CONCLUSIONS: This microsimulation model supports the clinical relevance of the reduction in alcohol consumption, and has estimated the extent of the public health benefit of treatment with nalmefene in patients with alcohol dependence and a high or very high drinking risk level.
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Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Alcoholismo/tratamiento farmacológico , Naltrexona/análogos & derivados , Salud Pública/métodos , Apoyo Social , Consumo de Bebidas Alcohólicas/efectos adversos , Consumo de Bebidas Alcohólicas/psicología , Alcoholismo/complicaciones , Alcoholismo/psicología , Ensayos Clínicos como Asunto/estadística & datos numéricos , Simulación por Computador , Europa (Continente) , Reducción del Daño/efectos de los fármacos , Humanos , Estudios Multicéntricos como Asunto/estadística & datos numéricos , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Evaluación de Procesos y Resultados en Atención de Salud/estadística & datos numéricos , Salud Pública/estadística & datos numéricosRESUMEN
BACKGROUND AND OBJECTIVE: When modelling the pathophysiology of a disease, it is important to select a modelling approach that can adequately replicate its course. The objective of this paper was to compare the outcomes obtained by the Markov and discrete-time microsimulation modelling approaches using nalmefene clinical trial data. METHODS: Markov and microsimulation modelling approaches assessing alcohol dependence treatment with psychosocial support with or without nalmefene were compared in terms of the modelled evolution of patients' alcohol consumption and the resulting occurrence of alcohol-attributable harmful events over 1 year. RESULTS: Comparison of the proportion of the modelled population at different levels of alcohol consumption over time revealed systematic differences arising from the different modelling techniques: a lower number of patients reaching abstinence, a higher number of patients at higher drinking levels, and, overall, a smoother evolution of alcohol consumption in the microsimulation. Reasons are discussed in the paper. While the models produced similar occurrences of alcohol-attributable harmful events as a whole, distinct results for the individual events were observed, explained by the specific pathophysiology of occurrence of these events and how their implementation was adapted to fit the limitations of the compared modelling approaches; however, these differences were only statistically significant for one of the eight events. CONCLUSIONS: For a general public health or health economic assessment of alcohol use disorders, it is possible to achieve similar results with the compared approaches. To assess a patients' disease course, taking into consideration alcohol-attributable harmful events, the microsimulation approach may provide more precise results. However, further external validation of the models is needed and this additional precision may be outweighed by the greater computational burden of a microsimulation approach.
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Consumo de Bebidas Alcohólicas/tratamiento farmacológico , Trastornos Relacionados con Alcohol/tratamiento farmacológico , Alcoholismo/tratamiento farmacológico , Naltrexona/análogos & derivados , Adulto , Femenino , Humanos , Naltrexona/administración & dosificaciónAsunto(s)
Melanosis/diagnóstico , Salud Mental , Calidad de Vida , Encuestas y Cuestionarios , Adulto , Comprensión , Características Culturales , Emociones , Femenino , Francia , Humanos , Lenguaje , Melanosis/etnología , Melanosis/psicología , Persona de Mediana Edad , Pacientes Ambulatorios , Valor Predictivo de las Pruebas , Psicometría , Recreación , Reproducibilidad de los Resultados , Conducta SocialRESUMEN
Reduction of long-term mortality risk, an important clinical outcome for people in alcohol dependence treatment, can rarely be established in randomized controlled trials (RCTs). We calculated the reduction in all-cause mortality risk using data from short-term (6 and 12 months) double-blind RCTs comparing as-needed nalmefene treatment to placebo, and mortality risks from meta-analyses on all-cause-mortality risk by reduction of drinking in people with alcohol dependence. A reduction in drinking in the RCTs was defined by shifts in drinking risk levels established by the European Medicines Agency. Results showed that the reduction of drinking in the nalmefene group was associated with a reduction in mortality risk by 8% (95% CI: 2%, 13%) when compared to the placebo group. Sensitivity analyses confirmed a significant effect. Thus comparing the difference between nalmefene and placebo in reduction in drinking levels with results on all-cause mortality risk from meta-analyses indicated a clinically relevant reduction in mortality risk. Given the high mortality risk of people with alcohol dependence, abstinence or a reduction in drinking have been shown to reduce mortality risk and should be considered treatment goals.
Asunto(s)
Alcoholismo/tratamiento farmacológico , Alcoholismo/mortalidad , Naltrexona/análogos & derivados , Método Doble Ciego , Femenino , Humanos , Masculino , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Placebos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The objective of this article was to investigate the effect of as-needed nalmefene on health-related quality of life (HRQoL) in patients with alcohol dependence, and to relate changes in drinking behavior and status to HRQoL outcomes. METHODS: This post hoc analysis was conducted on a pooled subgroup of patients with at least a high drinking risk level (men: >60 g/day; women: >40 g/day) who participated in one of two randomized controlled 6-month studies, ESENSE 1 and ESENSE 2. Patients received nalmefene 18 mg or placebo on an as-needed basis, in addition to a motivational and adherence-enhancing intervention (BRENDA). At baseline and after 12 and 24 weeks questionnaires for the Medical Outcomes Study (MOS) 36-item Short-Form Health Survey (SF-36), European Quality of life-5 Dimensions (EQ-5D) and the Drinker Inventory of Consequences (DrInC-2R) were completed. RESULTS: The pooled population consisted of 667 patients (nalmefene: 335; placebo: 332), with no notable between-group differences in baseline patient demographics/characteristics. At week 24, nalmefene had a superior effect compared to placebo in improving SF-36 mental component summary scores (mean difference [95% CI], p-value: 3.09 [1.29, 4.89]; p=0.0008), SF-36 physical component summary scores (1.23 [0.15, 2.31]; p=0.026), EQ-5D utility index scores (0.03 [0.00, 0.06]; p=0.045), EQ-5D health state scores (3.46 [0.75, 6.17]; p=0.012), and DrInC-2R scores (-3.22 [-6.12, 0.33]; p=0.029). The improvements in SF-36 mental component summary scores at week 24, and the DrInC-2R total score change from baseline to week 24, were significantly correlated to reductions in heavy drinking days and total alcohol consumption at week 24. CONCLUSIONS: As-needed nalmefene significantly improved almost all patient-reported HRQoL measures included in SF-36 and EQ-5D compared with placebo. These HRQoL gains were significantly correlated to reduced drinking behavior, as determined by reductions in heavy drinking days and total alcohol consumption.