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INTRODUCTION: The real-world effectiveness of the efmoroctocog alfa (recombinant FVIII Fc fusion protein, a rFVIIIFc) has been investigated in numerous studies, however, currently, there exists no comprehensive collection of the existing real-world evidence (RWE) on the performance of prophylactic use of rFVIIIFc. AIM: The aims of this systematic literature study were to identify, review, evaluate and collate the RWE of prophylactic rFVIIIFc for patients with haemophilia A reported in Europe. METHODS: We searched Medline and Embase from 2014 to February 2022 to identify publications reporting the effectiveness of rFVIIIFc in patients with haemophilia A. The outcomes of interest were annualised bleeding rates (ABR, AjBR, AsBR), injection frequency, factor consumption, adherence, development of inhibitors and quality-of-life measures. RESULTS: 46 eligible publications (eight full-text articles) were included. rFVIIIFc showed a low ABR in patients with haemophilia A. Studies assessing treatment switching from a standard half-life (SHL) treatment to rFVIIIFc found that the ABR and consumption were reduced in most patients. Studies assessing rFVIIIFc effectiveness reported a median ABR between 0.0 and 2.0 with median injections per week ranging between 1.8 and 2.4 and median doses between 60 and 105 IU/kg/week. Of the studies assessing inhibitor development, only one study reported an incidence of a low titre inhibitor, and no patients developed clinically significant inhibitors. CONCLUSION: rFVIIIFc prophylaxis treatment results in a low ABR across studies in patients with haemophilia A in a European real-world setting, which correlates with findings from clinical trials assessing the efficacy of rFVIIIFc in patients with haemophilia A.
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Hemofilia A , Humanos , Europa (Continente) , Fator VIII/uso terapêutico , Meia-Vida , Hemofilia A/tratamento farmacológico , Hemofilia A/prevenção & controle , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêuticoRESUMO
INTRODUCTION: The economic and clinical burden of haemophilia A is high. Primary prophylaxis with factor VIII replacement therapy is the recognised standard of care, but the emergence of non-factor therapies, such as emicizumab, is extending treatment options for people with haemophilia A. AIM: There are currently no direct comparisons of efficacy or cost between recombinant factor FVIII Fc-fusion protein efmoroctocog alfa (a recombinant factor FVIII Fc-fusion protein referred to herein as rFVIIIFc) and emicizumab; therefore, a cost-effectiveness model was developed to compare prophylactic treatment with rFVIIIFc versus emicizumab in patients with haemophilia A without inhibitors in the UK. METHODS: The cost-effectiveness model was based on a matching-adjusted indirect comparison and included male patients, aged ≥12 years, with haemophilia A without inhibitors. The model was designed as a Markov process with a flexible lifelong time horizon, and cost-effectiveness was presented as an incremental cost-effectiveness ratio. Base-case analysis and sensitivity analyses (including scenario analyses, one-way deterministic sensitivity analysis [DSA] and probability sensitivity analysis [PSA]) were performed using the following treatment strategies: individualised prophylaxis with rFVIIIFc and prophylaxis with emicizumab administered once weekly (scenario analyses used regimens of once every 2 weeks or once every 4 weeks). RESULTS: Base-case analysis, DSA and PSA indicated that, compared with emicizumab administered once weekly, rFVIIIFc individualised prophylaxis was the dominant treatment strategy, with lower costs, a greater number of quality-adjusted life years, and a lower number of bleeds. CONCLUSIONS: rFVIIIFc has proven efficacy and is cost-effective compared with emicizumab, providing clinicians with a viable treatment option to improve the health outcomes for adults and adolescents with haemophilia A in the UK.
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Fator VIII , Hemofilia A , Humanos , Adulto , Masculino , Adolescente , Fator VIII/uso terapêutico , Hemofilia A/terapia , Análise Custo-Benefício , Antígeno Prostático Específico/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Reino UnidoRESUMO
BACKGROUND: Atopic dermatitis (AD) is associated with a substantial burden on quality of life (QoL). OBJECTIVE: To evaluate the effects of tralokinumab on health-related QoL in patients with moderate-to-severe AD using patient-reported outcomes. METHODS: This was a phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study in adults with moderate-to-severe AD. The patients received subcutaneous tralokinumab or placebo (1:1:1:1) every 2 weeks for 12 weeks and class 3 topical corticosteroid cream or ointment at least once daily from the run-in to end of follow-up. Patient-reported outcome end points were change from baseline to week 12 in the Dermatology Life Quality Index (dermatology life quality index (DLQI); prespecified secondary objective), the Short Form 36 Health Survey (SF-36) version 2, and sleep interference numeric rating scale score (prespecified exploratory objectives). RESULTS: A total of 204 patients were randomized to placebo (n = 51) or tralokinumab (45 mg, n = 50; 150 mg, n = 51; 300 mg, n = 52). Tralokinumab 300 mg every 2 weeks improved total Dermatology Life Quality Index vs placebo at week 12 (placebo-adjusted mean change, -3.51 [95% confidence interval, -6.00 to -1.02]). At week 12, both the mental component summary (4.23 [0.98-7.47]) and the physical component summary (4.26 [1.83-6.69]) and all 8 domains of the Short Form 36 Health Survey were improved in patients treated with tralokinumab 300 mg vs placebo. Sleep interference was improved at week 12 with all tralokinumab doses vs placebo. CONCLUSION: Tralokinumab improved health-related QoL in patients with moderate-to-severe atopic dermatitis, providing further evidence of the value of targeting interleukin-13 in such patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02347176; https://clinicaltrials.gov/ct2/show/NCT02347176.
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Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Qualidade de Vida/psicologia , Sono/efeitos dos fármacos , Adolescente , Adulto , Idoso , Método Duplo-Cego , Feminino , Inquéritos Epidemiológicos , Humanos , Interleucina-13/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Placebos/uso terapêutico , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
PURPOSE: To develop a mapping algorithm for generating EQ-5D-5-level (EQ-5D-5L) utility scores from the Dermatology Life Quality Index (DLQI) in patients with atopic dermatitis (AD). METHODS: The algorithm was developed using data from 1232 patients from four countries participating in the National Health and Wellness Study. Spearman's rank correlation coefficient was used to evaluate the conceptual overlap between DLQI and EQ-5D-5L. Six mapping models (ordinary least squares [OLS], Tobit, three different two-part models, and a regression mixture model) were tested with different specifications to determine model performance and were ranked based on the sum of mean absolute error (MAE), and root mean squared error (RMSE). RESULTS: The mean DLQI score was 7.23; mean EQ-5D-5L score was 0.78; and there were moderate negative correlations between DLQI and EQ-5D-5L scores (p = - 0.514). A regression mixture model with total DLQI, and age and sex as independent variables performed best for mapping DLQI to EQ-5D-5L (RMSE = 0.113; MAE = 0.079). CONCLUSION: This was the first study to map DLQI to EQ-5D-5L exclusively in patients with AD. The regression mixture model with total DLQI, and age and sex as independent variables was the best performing model and accurately predicted EQ-5D-5L. The results of this mapping can be used to translate DLQI data from clinical studies to health state utility values in economic evaluations.
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Dermatite Atópica/epidemiologia , Qualidade de Vida/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
AIMS: To compare the cost-effectiveness of 2 glucagon-like peptide-1 (GLP-1) receptor agonists, liraglutide 1.8 mg and lixisenatide 20 µg, in the UK setting based on the LIRA-LIXI trial (NCT01973231). MATERIALS AND METHODS: Projections of costs (in 2015 pounds sterling [£]) and clinical outcomes were made over patient lifetimes using the IMS CORE Diabetes Model (IMS Health, Basel, Switzerland). The baseline cohort and treatment effects applied after initiation of GLP-1 receptor agonists were taken from the LIRA-LIXI trial. Future costs and clinical benefits were discounted at 3.5% annually. RESULTS: Liraglutide 1.8 mg was associated with improved discounted quality-adjusted life expectancy (8.87 vs 8.76 quality-adjusted life years [QALYs]) vs lixisenatide 20 µg. A greater reduction in glycated haemoglobin with liraglutide 1.8 mg led to fewer diabetes-related complications and delayed their time of onset. Liraglutide 1.8 mg was associated with increased total costs (£37 153 vs £36 174), driven by higher acquisition costs, but this was partially offset by savings from diabetes-related complications avoided (£26 969 vs £27 912). Liraglutide 1.8 mg was associated with an incremental cost-effectiveness ratio of £8901 per QALY gained vs lixisenatide 20 µg. CONCLUSIONS: Long-term projections suggest that treatment of patients with type 2 diabetes with liraglutide 1.8 mg is likely to be considered highly cost-effective compared with lixisenatide 20 µg treatment in the UK setting.
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Análise Custo-Benefício , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/economia , Liraglutida/economia , Peptídeos/economia , Adulto , Estudos de Coortes , Complicações do Diabetes/economia , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/economia , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Anos de Vida Ajustados por Qualidade de Vida , Reino UnidoRESUMO
Background: Hemophilia-associated bleeding and resultant joint pain and mobility restrictions can predispose patients to poor health-related quality of life (HRQoL). Therefore, efficacy of a treatment needs to address more than just annualized bleed rates. Objectives: Describe the evolution of HRQoL, pain, and activity in patients with hemophilia A, treated with efmoroctocog alfa prophylaxis. Design: A post hoc analysis from Kids A-LONG (NCT01458106), A-LONG (NCT01181128), and long-term extension study ASPIRE (NCT01454739) assessed change in pain and activity-related patient-reported outcomes (PROs). Methods: Physical health, pain, and HRQoL were assessed by PROs for a cumulative treatment duration of up to ~6 years. The primary endpoint was change from baseline in EuroQoL (EQ)-5D and Haemophilia Quality of Life Questionnaire (Haem-A-QoL). Results: 118 adult/adolescents and 71 pediatric patients were included. The proportion of adults and adolescents reporting no problem in the EQ-5D analysis of 'pain/discomfort' significantly increased from A-LONG baseline (35.04%; 41/117) to ASPIRE month 30 (44.68%; 21/47; p = 0.024). Mean (standard deviation) Haem-A-QoL subdomain scores for 'feeling' and 'physical health' at A-LONG baseline improved by -3.24 (15.13; p = 0.018) and -3.85 (23.07; p = 0.047), respectively, at study end. Proportion of pediatric patients reporting no problem on the EQ-5D analysis of 'pain/discomfort', significantly increased from A-LONG baseline (75.0%; 42/56) to ASPIRE baseline (95.56%; 43/45; p = 0.046). Satisfaction levels for pediatric patients were high at A-LONG baseline and maintained until study end. Conclusion: Long-term efmoroctocog alfa prophylaxis reduces pain and improves HRQoL in adult and adolescent patients with hemophilia A. In pediatric patients, it reduces perceived pain and maintains satisfaction levels. Trial registration: NCT01458106, NCT01181128, NCT01454739.
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INTRODUCTION: Patients with chronic refractory gout face a considerable burden of disease due to unexpected flares characterized by severe and debilitating pain, which can lead to chronic pain and joint damage. This study aimed to understand the symptoms and impacts of chronic refractory gout on health-related quality of life (HRQoL). METHODS: A targeted literature review was conducted to identify and review key articles describing the symptoms and impacts of gout, and articles examining the psychometric performance of the Medical Outcomes Survey Short Form-36 (SF-36) and Health Assessment Questionnaire-Disability Index (HAQ-DI) in gout. Qualitative interviews were conducted with 20 participants with chronic refractory gout. The results were used to develop the conceptual model and determine the appropriateness of the SF-36 and HAQ-DI in evaluating HRQoL in this population. RESULTS: Most frequently reported symptoms included bodily pain (n = 18, 90.0%), joint swelling (n = 18, 90.0%), joint tenderness (n = 18, 90.0%), and joint pain (n = 16, 80.0%). Most frequently reported impacts were difficulties climbing a flight (n = 20, 100.0%) or several flights of stairs (n = 20, 100.0%), climbing five steps (n = 19, 95.0%), completing chores (n = 19, 95.0%), and running errands and shopping (n = 19, 95.0%). All assessed items from SF-36 and HAQ-DI were reported by ≥ 25% (n = 5) of participants and mapped sufficiently to concepts elicited by participants. CONCLUSIONS: Patients with chronic refractory gout report symptoms and impacts that are highly bothersome and burdensome to everyday life. Items included in the HAQ-DI and SF-36 mapped directly to these symptoms and impacts and are relevant to understand the burden of disease of chronic refractory gout.
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OBJECTIVES: To describe clinical characteristics, factor consumption, and events of interest in patients with haemophilia A without inhibitors receiving prophylaxis in France, and the clinical impact of switching to Elocta® in this population. METHODS: This retrospective, observational study using the Système National des Données de Santé database, analysed data from patients with haemophilia A without inhibitors using prophylactic factor VIII (FVIII) replacement therapy during 2016-2019. Clinical characteristics, treatment patterns and switches, factor consumption, and rate of events of interest were determined. In a sub-cohort of patients treated with Elocta®, clinical characteristics, factor consumption, and rate of events of interest before and after switching to Elocta® were compared. RESULTS: For 545 patients, with mean age (standard deviation [SD]) 25.4 (17.8) years, Elocta® was the most used treatment. Bleeding events and articular non-bleeding events leading to hospitalization occurred in 15.4% and 13.9% of patients, respectively, and 9.9% of patients had surgeries or procedures related to haemophilic arthropathy. The mean (SD) FVIII product consumption was 344 (93) IU/kg/month for extended half-life treatment, and 331 (98) IU/kg/month for standard half-life products. For the sub-cohort of 146 patients, bleeding events (SD) decreased from 0.32 (2.2) to 0.09 (0.42) events/patient/year (p = 0.227) after switching to Elocta®. There was no statistically significant difference in rates of factor consumption or articular non-bleeding events before and after initiation of Elocta®. CONCLUSION: This study provides real-world insights that advance the understanding of treatment patterns and events of interest in patients with haemophilia A on prophylactic regimens in France.
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Hemofilia A , Humanos , Adulto , Hemofilia A/tratamento farmacológico , Hemofilia A/epidemiologia , Estudos Retrospectivos , Hemartrose , Cognição , Bases de Dados FactuaisRESUMO
Background: Pain is a common symptom of hemophilia that may adversely affect patients' quality of life (QoL). Previous post hoc analyses of prophylaxis with recombinant factor IX Fc fusion protein (rFIXFc) have been published for adults and adolescents, demonstrating improvements in health-related QoL (HRQoL) when assessed by the haemophilia-specific QoL (HaemAQoL) questionnaire. Objective: To describe in depth the evolution of QoL, pain- and activity-related domains and questions for pediatric, adolescent, and adult patients with hemophilia B treated with rFIXFc prophylaxis. Design: A post hoc analysis of data from a series of clinical trials. Methods: This post hoc, long-term analysis assessed patient-reported outcomes (PROs) from the Kids B-LONG (NCT01440946: pediatric) and B-LONG (NCT01027364: adults and adolescents) parent studies and the B-YOND (NCT01425723: all age groups) extension study. Results: Ninety-two adult and adolescent patients that started in the B-LONG study were assessed, with a median (range) duration of follow-up of 58.9 (0.0-78.4) months. The Haem-A-QoL total score was significantly reduced from baseline by 4.45 (p ⩽ 0.01), as were the subdomains 'physical health' (9.10; p = 0.001), 'sports and leisure' (11.25; p ⩽ 0.01), 'treatment' (2.69; p = 0.05), and 'view of self' (5.81; p = 0.002). Thirty pediatric patients that started in the Kids B-LONG study were assessed, with a median (min-max) duration of follow-up of 36.7 (9.0-59.9) months. The high level of satisfaction demonstrated by the PROs at baseline was maintained. Conclusion: rFIXFc prophylaxis reduced perceived pain and increased levels of physical activity with sustained, long-term improvements in QoL in adult and adolescent patients with hemophilia B and maintained high QoL scores in pediatric patients.
Helping to reduce pain and increase physical activity in patients with hemophilia B People with hemophilia B do not produce factor IX (FIX) that works properly, so they need to be given additional FIX to help their blood clot. Recombinant factor IX Fc fusion protein (rFIXFc), is an extended half-life (meaning it remains active for longer than standard, unmodified FIX) treatment for hemophilia B. People with hemophilia B can experience episodes of bleeding, which can result in other symptoms, including pain, difficulty participating in sport, and poor mental health. This study shows that regularly taking rFIXFc over approximately 5 years to prevent or treat bleeds could also help to make these other symptoms better.
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INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory disorder which, despite recent therapeutic developments, leads to significant burden and morbidity, impacting on daily functioning, physical and mental health, and health-related quality of life. The objective of this study was to investigate the impact of new therapeutic approaches in the treatment of moderate to severe AD and quantify subsequent differences in disease and symptom control. METHODS: Data were drawn from the 2018 Adelphi US AD Disease Specific Programme™ (DSP™), a cross-sectional survey of physicians (n = 150) and their patients with a history of moderate to severe AD (n = 749, 52.7% female, 72.1% white, mean age 40.1 ± 16.3 years). Inadequately controlled AD as rated by the physician was defined as currently flaring, and/or deteriorating/changeable AD and/or physician dissatisfaction with disease control on current treatment. RESULTS: The overall inadequate control rate was 42.3%, an improvement from 58.7% as identified in the 2014 DSP survey. The proportion of inadequately controlled patients increased as physician subjective severity (ranked from mild through to severe) increased; 15.4% of patients classified as having mild disease were inadequately controlled, compared to 94.5% of patients classified with severe disease. Relative to patients with controlled disease, patients with inadequately controlled disease were more likely to be unemployed, reported more frequent flares, and had a greater burden of symptoms and worse quality of life measures including itch, stress, anxiety, depression, and sleep disturbance (all p < 0.0001). CONCLUSION: Despite the introduction of new therapies, the burden and impact of AD and lack of symptom control, although reduced compared with previous studies, still remains high.
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BACKGROUND: The use of prescription anti-obesity medication (AOM) is becoming increasingly common as treatment options grow and become more accessible. However, AOM may not be without a wide range of potentially negative impacts on patient functioning and well being. The Treatment Related Impact Measure (TRIM-Weight) is an obesity treatment-specific patient reported outcomes (PRO) measure designed to assess the key impacts of prescription anti-obesity medication. This paper will present the validation findings for the TRIM-Weight. METHODS: The online validation battery survey was administered in four countries (the U.S., U.K., Australia, and Canada). Eligible subjects were over age eighteen, currently taking a prescription AOM and were currently or had been obese during their life. Validation analyses were conducted according to an a priori statistical analysis plan. Item level psychometric and conceptual criteria were used to refine and reduce the preliminary item pool and factor analysis to identify structural domains was performed. Reliability and validity testing was then performed and the minimally importance difference (MID) explored. RESULTS: Two hundred and eight subjects completed the survey. Twenty-one of the 43 items were dropped and a five-factor structure was achieved: Daily Life, Weight Management, Treatment Burden, Experience of Side Effects, and Psychological Health. A-priori criteria for internal consistency and test-retest coefficients for the total score and all five subscales were met. All pre-specified hypotheses for convergent and known group validity were also met with the exception of the domain of Daily Life (proven in an ad hoc analysis) as well as the 1/2 standard deviation threshold for the MID. CONCLUSION: The development and validation of the TRIM-Weight has been conducted according to well-defined principles for the creation of a PRO measure. Based on the evidence to date, the TRIM-Weight can be considered a brief, conceptually sound, valid and reliable PRO measure.
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Fármacos Antiobesidade/uso terapêutico , Peso Corporal , Obesidade/tratamento farmacológico , Avaliação de Resultados em Cuidados de Saúde/métodos , Fármacos Antiobesidade/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos TestesRESUMO
: The aim of this study was to conduct 3 literature reviews to examine the impact of atopic dermatitis (AD) and chronic hand eczema (CHE) on health-related quality of life (HRQoL) compared with other chronic conditions by comparing reported utility scores of 4 commonly used generic HRQoL instruments. A systematic search was performed using PubMed, ScienceDirect, MEDLINE, EMBASE, Health Technology Assessment database, and ScHARRHUD. Inclusion criteria included, but were not limited to, patients of any age, studies from any location, publications reporting utility data based on EuroQoL 5 dimensions, the EuroQoL 5-dimension Visual Analog Scale, the Short-Form Health Survey, and the Short-Form 6 Dimensions in the English language. Inclusion criteria were met by 16 articles for AD, 25 articles for chronic conditions, and 9 articles for CHE. The findings of this review highlight that the disutility and loss in HRQoL of patients with AD and CHE are similar to or higher than other chronic conditions, such as cancer or hepatitis.
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Dermatite Atópica/fisiopatologia , Dermatoses da Mão/fisiopatologia , Qualidade de Vida , Doença Crônica , Dermatite Atópica/psicologia , Eczema/fisiopatologia , Eczema/psicologia , Dermatoses da Mão/psicologia , HumanosRESUMO
AIMS: This retrospective, longitudinal study characterised 2430 adults (mean age 40.8±16.1years) with newly diagnosed type 1 diabetes (T1D) over the first 5years of insulin treatment. METHODS: Data from 1year pre- and up to 5 years post-insulin initiation were extracted from the UK Clinical Practice Research Datalink (1990-2013). Baseline HbA1c, BMI and Charlson comorbidity index (CCI) score were compared with data at 1, 2, 3 and 5 years. RESULTS: Mean HbA1c decreased significantly from baseline 95±32.8mmol/mol (10.8±3.0%) to 61±21.9mmol/mol (7.7±2.0%) at 1year, remaining significantly lower at 2, 3 and 5 years (p<0.0001). One year after initiating insulin, only 6.3% of patients had HbA1c <48mmol/mol (<6.5%). There was no further improvement in HbA1c after 1year. Mean BMI increased significantly from baseline 25.3±5.5kg/m2 to 27.2±5.8kg/m2 at 1year; p<0.0001), remaining significantly higher thereafter, with over two-thirds having overweight/obesity by year 5. Mean CCI score increased significantly (1.32, baseline; 1.46, year 1; 1.75, year 5). CCI patterns were similar within BMI and HbA1c strata. CONCLUSIONS: More intensive support to reach and maintain glycaemic targets soon post-diagnosis, while avoiding weight gain, and prevention and optimal management of comorbidities are warranted.
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Glicemia/efeitos dos fármacos , Índice de Massa Corporal , Diabetes Mellitus Tipo 1/tratamento farmacológico , Controle Glicêmico , Hipoglicemiantes/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Glicemia/metabolismo , Comorbidade , Bases de Dados Factuais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Insulina/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia , Adulto JovemRESUMO
Patient-reported outcome measures (PROMs) provide an important complement to physician-assessed clinical outcome measures in dermatologic diseases such as atopic dermatitis (AD) and chronic hand eczema (CHE). AD and CHE are chronic and relapsing inflammatory skin conditions that often co-occur. While both diseases result in various signs and symptoms that are burdensome and can negatively affect patients' lives, there may be distinct differences in the signs, symptoms, burden, and health-related quality of life (HRQOL) impact of these diseases. The objective of this study was to identify and evaluate PROMs used in studies of AD and CHE. The aim was to explore the assessment of key symptoms and impacts, and identify any gaps in the measures in use. A structured review of the PubMed database was conducted to identify PROMs used or developed for use in AD or CHE. The Dermatology Life Quality Index (DLQI), the Pruritus/Itch Numeric Rating Scale (NRS), the Patient-Oriented Eczema Measure (POEM), and the Quality of Life in Hand Eczema Questionnaire (QOLHEQ) were identified and reviewed in detail. With these measures, the AD and CHE symptoms and impacts most commonly evaluated in the literature include dermatology-related HRQOL in the domains of symptoms and feelings, daily activities, leisure, work and school, personal relationships, and adverse effects; pruritus; sleep disturbance; AD-specific symptoms (dryness, itching, flaking, cracking, bleeding, and weeping/oozing); and CHE-specific symptoms (pain, itch, fissuring, redness, bleeding, and dryness). A review of regulatory labels of drugs approved for AD by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) found that, among the four measures reviewed, the Pruritus NRS was included in the FDA and EMA labels for dupilumab, the DLQI was included in the EMA labels for dupilumab and tacrolimus, and the POEM was included in the EMA label for dupilumab. Key symptoms of AD (e.g. itching, flaking, cracking) and CHE (e.g. pain, itching, fissuring) are increasingly being assessed with PROMs; however, primary endpoints in clinical trials are often based on clinician-reported outcome measures. As therapeutic strategies in dermatology are targeted at specific dermatologic symptoms and diseases affecting specific sites (e.g. CHE), future research should explore patients' experiences with these symptoms and sites and the changes with treatment that are most meaningful to them.
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Doença Crônica , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/fisiopatologia , Eczema/tratamento farmacológico , Eczema/fisiopatologia , Mãos/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Adulto , HumanosRESUMO
OBJECTIVE: Acute postprandial hyperglycemia (aPPHG) is often symptomatic and can be associated with behavioral changes such as impaired working memory and attention. However, there is little evidence of the impact of aPPHG on the daily lives of patients. The aim of this study was to explore the frequency and severity of aPPHG episodes and their impact on daily functioning in people with insulin-treated diabetes. METHODS: Adults (n = 1200) with insulin-treated diabetes mellitus type 1 (T1DM) or 2 (T2DM), most of whom experienced aPPHG, were recruited to complete an online cross-sectional survey in the USA and UK. The survey captured self-reported severity and frequency of aPPHG episodes and included a newly developed questionnaire (aPPHG-Q) assessing the impact of aPPHG episodes on patients' daily lives. Data was analyzed separately according to diabetes type and country. Regression analyses were used to assess the relationship between severity or frequency and scores on the aPPHG-Q. RESULTS: Between 70% and 86% of USA, and 87% and 88% of UK participants reported experiencing aPPHG episodes. Increasing frequency and severity of aPPHG episodes were associated with worse scores on the aPPHG-Q in patients with both T1DM and T2DM in both countries (p < .014) on all subscale scores (excluding the worry and concerns scores for T1DM in the UK), although the magnitude of the association was smaller for aPPHG frequency. CONCLUSIONS: Increased severity and frequency of aPPHG episodes in patients with insulin-treated diabetes is associated with greater burden and experience of symptoms, and can negatively impact daily functioning.
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Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Hiperglicemia/epidemiologia , Período Pós-Prandial/fisiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Atopic dermatitis (AD) is a pruritic or painful dermatologic disease characterized by xerosis and eczema lesions. The symptoms/signs of AD can significantly impact patients' health-related quality of life (HRQoL). This study aimed to qualitatively explore the adult and adolescent experience of AD. A targeted literature review and qualitative concept elicitation interviews with clinicians (n = 5), adult AD patients (n = 28), and adolescent AD patients (n = 20) were conducted to elicit AD signs/symptoms and HRQoL impacts experienced. Verbatim transcripts were analyzed using thematic analysis. Twenty-nine symptoms/signs of AD were reported, including pruritus, pain, erythema, and xerosis. Atopic dermatitis symptoms/signs were reported to substantially impact HRQoL. Scratching was reported to influence the experience of symptoms and HRQoL impacts. Four proximal impacts (including discomfort and sleep disturbance) were reported. Ten domains of distal impact were reported, including impacts on psychological and social functioning and activities of daily living. A conceptual model was developed to summarize these findings. This study highlights the range of symptoms and HRQoL impacts experienced by adults and adolescents with AD. To our knowledge, this study was first to explore the lived experience of AD in both adult and adolescent patients, providing valuable insight into the relatively unexplored adolescent experience of AD.
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Efeitos Psicossociais da Doença , Dermatite Atópica/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Atividades Cotidianas , Adolescente , Adulto , Dermatite Atópica/complicações , Feminino , Comportamentos Relacionados com a Saúde , Humanos , MasculinoRESUMO
AIMS: To determine the comparative efficacy and safety of liraglutide and dipeptidyl peptidase-4 (DPP-4) inhibitors as antidiabetics for Japanese patients with uncontrolled type 2 diabetes (T2DM). METHODS AND MATERIALS: We searched for randomized controlled trials (RCTs) evaluating outcomes among Japanese adults with uncontrolled T2DM and including liraglutide or DPP-4 inhibitors up to August 2016. We extracted data on trial and patient characteristics, and the following outcomes: HbA1c, weight, patients meeting HbA1c <7%, patients experiencing hypoglycemic events, microalbuminuria, estimated glomerular filtration rate (eGFR) and creatinine. We synthesized data using network meta-analyses (NMA) using a Bayesian framework. Continuous outcomes were modeled using normal likelihoods and an identity link, while dichotomous outcomes were modeled using a binomial likelihood and a logit link. RESULTS: The systematic literature review yielded 39 publications pertaining to 38 trials. A total of 27 trials (5032 patients) reported change in HbA1c at 12 weeks and at 24 weeks 9 trials (2091 patients). All treatments showed statistically significant reductions in HbA1c relative to placebo at 12 and 24 weeks. Liraglutide 0.9 mg was statistically superior to all DPP-4 interventions (vildagliptin, sitagliptin, linagliptin, alogliptin, teneligliptin, trelagliptin and omarigliptin) at 12 weeks and 24 weeks among those reporting. Treatments were not statistically differentiable with respect to weight change and risk of hypoglycemia. Finally, no comparisons of eGFR and microalbuminuria were conducted, as this data was reported in too few trials to conduct analyses. LIMITATIONS: Some important outcomes were limited by poor reporting (eGFR and microalbuminuria) or low event rates (hypoglycemia). The follow-up time was relatively short. Clinically, the 24 week time point is more important as it demonstrates more sustained results. CONCLUSIONS: Our research suggests that liraglutide 0.9 mg offers a more efficacious treatment option for T2DM than the DPP-4 inhibitors among adult Japanese patients and that it is a viable option for this population.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Liraglutida/uso terapêutico , Adulto , Feminino , Hemoglobinas Glicadas , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/uso terapêutico , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Maintaining glycemic control is the key treatment target for patients with type 2 diabetes mellitus. In addition, the glucagon-like peptide-1 (GLP-1) receptor agonists may be associated with other favorable treatment characteristics, such as reduction in body weight and reduced risk of hypoglycemia compared with traditional diabetes interventions. The aim of the present analysis was to compare the long-term cost-effectiveness of 2 GLP-1 receptor agonists, liraglutide 1.8 mg and lixisenatide 20 µg (both administered once daily), in the treatment of patients with type 2 diabetes failing to achieve glycemic control with metformin monotherapy in the Italian setting. METHODS: The IMS CORE Diabetes Model was used to project long-term clinical outcomes and subsequent costs (in 2015 Euros []) associated with liraglutide 1.8 mg versus lixisenatide 20 µg treatment in a cohort with baseline characteristics derived from the open-label LIRA-LIXI trial (Efficacy and Safety of Liraglutide Versus Lixisenatide as Add-on to Metformin in Subjects With Type 2 Diabetes; NCT01973231) over patient lifetimes from the perspective of a health care payer. Efficacy data were taken from the 26-week end points of the same trial, including changes in glycated hemoglobin, body mass index, serum lipid levels, and hypoglycemic event rates. Outcomes projected included life expectancy, quality-adjusted life expectancy, cumulative incidence and time to onset of diabetes-related complications, and direct medical costs. Outcomes were discounted at 3% annually, and sensitivity analyses were performed. FINDINGS: Liraglutide 1.8 mg was associated with improved discounted life expectancy (14.07 vs 13.96 years) and quality-adjusted life expectancy (9.18 vs 9.06 quality-adjusted life years [QALYs]) compared with lixisenatide 20 µg. These improvements were mostly attributable to a greater reduction in glycated hemoglobin level with liraglutide 1.8 mg versus lixisenatide 20 µg, leading to reduced incidence and increased time to onset of diabetes-related complications. Compared with lixisenatide 20 µg, liraglutide 1.8 mg was associated with increased total costs over patient lifetimes (41,623 vs 41,380), but this was offset by lower costs of treating diabetes-related complications (26,682 vs 27,476). Liraglutide 1.8 mg was associated with an incremental cost-effectiveness ratio of 2001 per QALY gained versus lixisenatide 20 µg. At a willingness-to-pay threshold of 30,000 per QALY gained, liraglutide 1.8 mg had a probability of 77.2% of being cost-effective. IMPLICATIONS: Based on long-term projections, liraglutide 1.8 mg is likely to be considered cost-effective compared with lixisenatide 20 µg for the treatment of patients with type 2 diabetes in Italy.
Assuntos
Diabetes Mellitus Tipo 2/economia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/economia , Liraglutida/economia , Peptídeos/economia , Índice de Massa Corporal , Análise Custo-Benefício , Complicações do Diabetes/tratamento farmacológico , Complicações do Diabetes/economia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemia/economia , Hipoglicemiantes/uso terapêutico , Itália , Expectativa de Vida , Liraglutida/uso terapêutico , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Peptídeos/uso terapêutico , Anos de Vida Ajustados por Qualidade de VidaRESUMO
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists are used successfully in the treatment of patients with type 2 diabetes as they are associated with low hypoglycemia rates, weight loss and improved glycemic control. This study compared, in the Spanish setting, the cost-effectiveness of liraglutide 1.8 mg versus lixisenatide 20 µg, both GLP-1 receptor agonists, for patients with type 2 diabetes who had not achieved glycemic control targets on metformin monotherapy. METHODS: The IMS CORE Diabetes Model was used to project clinical outcomes and costs, expressed in 2015 Euros, over patient lifetimes. Baseline cohort data and treatment effects were taken from the 26-week, open-label LIRA-LIXI™ trial (NCT01973231). Treatment and management costs of diabetes-related complications were retrieved from published sources and databases. Future benefits and costs were discounted by 3% annually. Sensitivity analyses were conducted. RESULTS: Compared with lixisenatide 20 µg, liraglutide 1.8 mg was associated with higher life expectancy (14.42 vs. 14.29 years), higher quality-adjusted life expectancy [9.40 versus 9.26 quality-adjusted life years (QALYs)] and a reduced incidence of diabetes-related complications. Higher acquisition costs resulted in higher total costs for liraglutide 1.8 mg (EUR 42,689) than for lixisenatide 20 µg (EUR 42,143), but these were partly offset by reduced costs of treating diabetes-related complications (EUR 29,613 vs. EUR 30,636). Projected clinical outcomes and costs resulted in an incremental cost-effectiveness ratio of EUR 4113 per QALY gained for liraglutide 1.8 mg versus lixisenatide 20 µg. CONCLUSIONS: Long-term projections in the Spanish setting suggest that liraglutide 1.8 mg is likely to be cost-effective compared with lixisenatide 20 µg in type 2 diabetes patients who have not achieved glycemic control targets on metformin monotherapy. Liraglutide 1.8 mg presents a clinically and economically attractive treatment option in the Spanish setting.
RESUMO
INTRODUCTION: In clinical trials, liraglutide has proven to be an effective drug for the treatment of type 2 diabetes mellitus (T2DM). The real-world effectiveness of liraglutide has been investigated in numerous studies. The aim of this systematic literature review is to collate evidence on the real-world clinical effectiveness of liraglutide. METHODS: A review of publications from Medline, EMBASE, the Cochrane Library, and conference proceedings was conducted to identify observational studies that assessed the clinical effectiveness of liraglutide in real-world clinical practice. This review was conducted according to the National Institute of Health and Care Excellence (NICE) guidance. No language or time limits were applied, except to the conference proceedings (2013-2015). Endpoints for data extraction were decided a priori. Study quality appraisal was done for full-text journal articles. RESULTS: Of 124 publications included in the review, 43 were full-text articles. Liraglutide significantly reduces glycated hemoglobin (HbA1c) within 6 months of initiating treatment (mean change in HbA1c from baseline: -0.9% to -2.2%; HbA1c <7.0%: 29.5-65.0%). The NICE composite endpoint (HbA1c reduction ≥1% and weight reduction ≥3%) was met in 16.9-47.0% of patients with liraglutide treatment. Liraglutide therapy led to a mean change in absolute weight from baseline of -1.3 to -8.65 kg. Liraglutide treatment was well tolerated in patients with T2DM. The rate of occurrence of hypoglycemia with liraglutide monotherapy was ≤0.8%. Hypoglycemia was more common in patients taking antidiabetic medications (0.0-15.2%) together with liraglutide. The beneficial glycemic and weight effect of liraglutide therapy in patients with T2DM was maintained for at least 12 months. CONCLUSION: Evidence from observational studies reflecting real-world clinical practice demonstrates that liraglutide therapy improves glycemic control with a low risk of hypoglycemia, and is associated with significant weight loss in patients with T2DM. These observations are consistent with clinical trial findings. FUNDING: Novo Nordisk A/S, Søborg, Denmark.