Tafamidis medication adherence and persistence in patients with transthyretin amyloid cardiomyopathy in Japan.

AIMS: This study aimed to describe baseline characteristics and adherence among patients with transthyretin amyloid cardiomyopathy (ATTR-CM) treated with tafamidis (VYNDAQEL®) in Japan using the Japanese Medical Data Vision (MDV) database. METHODS AND RESULTS: This study was a non-interventional, retrospective cohort study of adult (≥18 years old) patients in the Japanese MDV claims database diagnosed with ATTR-CM and with at least two tafamidis prescriptions of dose strength 4 × 20 mg/day between 1 March 2019 and 31 August 2021. The date of the first prescription was defined as the index date, with follow-up time defined as the time between the first and last prescription plus the days' supply from the last refill. Baseline characteristics were assessed during a 12 month pre-index period. Adherence was measured using two metrics: (i) the modified medication possession ratio (mMPR), calculated by taking the sum of days supplied for all fills within the follow-up period, divided by the number of days of follow-up, and reported as a percentage, with patients classified as adherent with an mMPR of ≥80%, and (ii) the proportion of days covered (PDC), calculated by taking the total number of days' supply dispensed during the follow-up period divided by the number of days of follow-up, adjusting for any days' supply overlap. A total of 210 patients were identified; the mean (standard deviation) age of the cohort was 77 (5.9) years, and the majority (89%) were male. The most common baseline cardiovascular comorbidities were heart failure (85%), ischaemic heart disease (66%), hypertensive diseases (49%), and diabetes (35%); 75% of patients received heart failure medications in the 12 months prior to index, with the most common being beta-blockers (49%), diuretics (48%), angiotensin receptor blockers (30%), angiotensin-converting enzyme inhibitors (22%), and sodium-glucose cotransporter-2 inhibitors (8.1%). Over an average 14 month follow-up, mean mMPR was 96% with a median of 100% [inter-quartile range (IQR): 97-101%]; 93% of patients were adherent (defined as an mMPR ≥ 80%). In the same follow-up period, mean PDC was 93.6% with a median of 99% (IQR: 93-100%). Persistence was high with 78% of patients having a 0 day gap between prescription refills. CONCLUSIONS: This study found high adherence rates to tafamidis in this real-world Japanese patient population. Adherence rates in this study were similar to those reported by the tafamidis clinical trial and a previously published US commercial claims adherence analysis. Further studies should be conducted to assess the impact of real-world adherence on real-world outcomes.

Burden of untreated transthyretin amyloid cardiomyopathy on patients and their caregivers by disease severity: results from a multicenter, non-interventional, real-world study.

Background: The humanistic burden of transthyretin amyloid cardiomyopathy (ATTR-CM) is poorly defined. Methods: An international study to comprehensively characterize the burden of ATTR-CM on patients naïve to disease-modifying therapy and their unpaid primary caregivers using study-specific and established surveys (patients: Kansas City Cardiomyopathy Questionnaire Overall Summary [KCCQ-OS], 12-Item Short Form Health Survey [SF-12], Hospital Anxiety and Depression Scale [HADS], Patient-Reported Outcomes Measurement Information System [PROMIS] Fatigue and Dyspnea; caregivers: SF-12, HADS, PROMIS Fatigue, Zarit Burden Interview [ZBI]). All data were summarized descriptively. Results: 208 patient and caregiver pairs were included. 86% of patients were male, median age was 81 years, and 91% (141/155 with genetic testing) had wild-type ATTR-CM. Patient responses characterized the mental and physical burden of ATTR-CM, which was numerically higher among those who were New York Heart Association (NYHA) class III (n = 43) vs. class I/II (n = 156). NYHA class III patients had particularly low KCCQ-OS (36) and SF-12 physical component (27) scores, and 67% had a HADS depression score ≥8. Caregivers (median age 68 years; 85% female; 59% spouse of the patient; median duration of caregiving 1.5 years) reported that NYHA III patients more frequently required help with a range of physical activities than NYHA class I/II patients. 51% of caregivers to NYHA class III patients reported at least a mild-to-moderate burden in the ZBI. A plain language summary of this paper can be found as a supplemental material. Conclusions: Untreated ATTR-CM is a burden to both patients and their caregivers.

A plain language summary on preventing fungal infections with isavuconazole in people with blood-related conditions.

WHAT IS THIS SUMMARY ABOUT?: People with blood-related conditions have a higher chance of getting invasive fungal infections (IFIs). IFIs are severe fungal infections that can lead to death. Only a few medications, known as antifungals, exist that can be used to prevent IFIs, and sometimes they can cause very bad side effects. Isavuconazole is an antifungal which has been approved to treat IFIs, but it has not been approved to prevent IFIs. In this study, we reviewed published studies that looked at how well isavuconazole prevented IFIs in people who have a higher chance of getting IFIs. WHAT WERE THE RESULTS?: This review showed that isavuconazole could be effective at preventing IFIs in people with blood-related conditions, as well as being a safe medication. WHAT DO THE RESULTS OF THE STUDY MEAN?: Isavuconazole can prevent IFIs in people who have a higher chance of getting IFIs. Guidelines should consider that patients need new antifungals to prevent IFIs, and more research needs to be done to see which medicines work best, and which have fewer side effects. Clinical Trial Registration: Please note that 7 studies included in this review were planned studies (1 prospective, 6 retrospective), 2 were real- world studies, 1 of which was registered as a clinical trial NCT03019939 (ClinicalTrials.gov).

Improved long-term survival with tafamidis treatment in patients with transthyretin amyloid cardiomyopathy and severe heart failure symptoms.

AIM: The value of disease-modifying therapies (such as tafamidis) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and severe heart failure symptoms has been debated. This study assessed long-term all-cause survival in patients with New York Heart Association (NYHA) class III symptoms in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) long-term extension (LTE) study. METHODS AND RESULTS: At the baseline of ATTR-ACT, 55/176 (31.3%) patients receiving tafamidis 80 mg and 63/177 (35.6%) receiving placebo had NYHA class III symptoms. After 30 months of treatment, patients could join an ongoing LTE study to receive open-label tafamidis. In an interim analysis of the LTE study (August 2021), all-cause mortality was lower among patients with NYHA class III symptoms who received continuous tafamidis in ATTR-ACT and the LTE study (hazard ratio 0.64; 95% confidence interval 0.41-0.99; median follow-up: 60 months), as compared with those who received placebo in ATTR-ACT and tafamidis in the LTE study (median follow-up: 56 months). Similar findings were observed in patients with NYHA class I/II symptoms at baseline (0.50; 0.35-0.73; tafamidis 80 mg n = 121; placebo n = 114; median follow-up of 61 and 60 months, respectively). CONCLUSION: We observed reduced all-cause mortality with continuous tafamidis treatment compared with delayed tafamidis treatment (placebo then tafamidis) in patients with NYHA class III symptoms at baseline over a median follow-up of ∼5 years. These findings demonstrate the value of tafamidis treatment in patients with ATTR-CM and severe heart failure symptoms, and emphasize the importance of early treatment. CLINICAL TRIAL REGISTRATIONS: ClinicalTrials.gov NCT01994889 and NCT02791230.

Matching-Adjusted Indirect Comparisons of Lorlatinib Versus Chemotherapy for Patients With Second-Line or Later Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

OBJECTIVES: This study aimed to compare the relative efficacy of lorlatinib, an anaplastic lymphoma kinase-tyrosine kinase inhibitor, with chemotherapy, for patients with second-line or later advanced anaplastic lymphoma kinase-positive non-small cell lung cancer. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). METHODS: Evidence for lorlatinib was informed by the single-arm phase I/II trial B7461001. A systematic literature review (SLR) was performed to identify OS and PFS data for chemotherapy. Unanchored matching-adjusted indirect comparisons (MAICs) between lorlatinib and chemotherapy (pemetrexed/docetaxel, platinum-based, or systemic therapy) were performed. RESULTS: The SLR identified 3 relevant studies reporting PFS. Lorlatinib was associated with a significant decrease in the hazard of progression versus the 2 types of chemotherapy assessed. For PFS, the MAIC of lorlatinib versus the combined treatment arm of docetaxel or pemetrexed resulted in an adjusted hazard ratio (HR) of 0.22 (95% confidence interval [CI] 0.15-0.31). When lorlatinib was compared with platinum-based chemotherapy through an MAIC, the adjusted HR for PFS was 0.40 (95% CI 0.29-0.55). An exploratory comparison was performed for OS with evidence for systemic therapy (assumed equivalent to chemotherapy) not identified in the SLR. Lorlatinib provided a significant decrease in hazard of death (OS) versus systemic therapy, with HRs ranging from 0.12 (95% CI 0.05-0.27) to 0.43 (95% CI 0.27-0.60). CONCLUSIONS: Lorlatinib demonstrated a significant improvement in PFS compared with chemotherapy, although limitations in the analyses were identified. The evidence informing OS comparisons was highly limited but suggested benefit of lorlatinib compared with systemic therapy.

Effectiveness and safety of isavuconazole prophylaxis for invasive fungal infections in the haematologic setting.

OBJECTIVES: Patients with haematologic malignancies are at high risk of developing invasive fungal infections (IFIs). Current guidelines recommend the use of azoles for IFI prophylaxis; however, in many clinical situations, antifungal prophylaxis is used off-label. We conducted a systematic literature review to provide haematologists with the available evidence on the effectiveness and safety of isavuconazole in IFI prophylaxis in interventional and real-world, observational studies. METHODS: Embase, MEDLINE and Cochrane Library databases, and relevant conference proceedings and clinical trial registries, were searched for studies on the effectiveness and safety of isavuconazole prophylaxis in adults at high risk of IFIs. Studies were assessed for inclusion and risk of bias. RESULTS: Nine studies were eligible for inclusion in the review, eight of which were in haematologic populations (patients undergoing haematopoietic stem cell transplantation or with acute myeloid leukaemia or myelodysplastic syndromes; n = 5) or included haematologic populations (n = 3). Evidence from these studies suggests isavuconazole is effective for IFI prophylaxis in the haematologic setting. However, the studies frequently lacked safety data, most were based on small patient populations from single centres and risk of bias could not be assessed for five studies. DISCUSSION: These findings provide evidence for isavuconazole as an alternative azole for prophylaxis in high-risk populations. Limitations include lack of applicability of risk of bias assessment tools, level of filtering applied in the search strategy and focus on English-language publications. CONCLUSION: Isavuconazole may be an effective azole for IFI prophylaxis in high-risk haematologic populations, although further studies are needed.

Real-World Financial and Clinical Impact of Diagnostic-Driven and Empirical-Treatment Strategies in High-Risk Immunocompromised Patients with Suspected Aspergillus Infection in the United Kingdom.

A diagnostic-driven (DD) treatment strategy has proven successful for treating invasive fungal infections (IFIs) caused by Aspergillus. However, uptake of this treatment strategy is not fully embraced. This study compares the economic and clinical impact of DD and empirical-treatment (ET) strategies used within hospitals. Methods: a decision-analytic model was developed to compare costs and clinical outcomes associated with ET or a DD strategy of identifying infections caused by Aspergillus via galactomannan-antigen testing or Aspergillus polymerase chain reaction (PCR) in neutropenic patients with unexplained fever. Patients were treated prophylactically with antifungal treatments as seen in United Kingdom (UK) hospitals. The IFI incidence, response, mortality, resource use, and adverse events were obtained from meta-analyses and other clinical studies. Analyses were performed from the U.K. hospital perspective, and costs were obtained from standard costing sources. Although diagnostic-testing costs increased, total cost and length of stay were reduced by £1,121 and 1.54 days when treating via a DD strategy. Intensive care and general ward days accounted for > 40% of total costs and > 58% of the cost reduction came from reduced antifungal costs. Treating with a DD strategy reduced the number of patients being treated with antifungal agents while survival was increased. Thus, a DD strategy was cost savings (-£136,787 cost per death avoided) compared with an ET strategy. Conclusion: this study suggests that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever. IMPORTANCE Patients at risk of invasive fungal infections (IFIs), such as Aspergillus spp., tend to be immunocompromised and usually take several medications which may generate many side effects. Prescribing is further complicated by comorbidities, drug interactions and challenges accessing diagnostics. Therefore, adding another agent may be neither straightforward nor the best option for these types of patients. A diagnostic-driven (DD) treatment strategy has proven successful for treating IFIs. However, uptake of this treatment strategy is not fully embraced in clinical practice perhaps because this strategy is thought to be more costly and/or to result in higher mortality relative to treating empirically. We developed a decision-analytic model to examine the impact of these 2 strategies on costs and health outcomes. This study indicates that incorporating a DD strategy as the preferred treatment protocol may be a cost-saving and clinically improved treatment strategy for managing neutropenic patients with unexplained fever.

Health-related quality of life in hereditary transthyretin amyloidosis polyneuropathy: a prospective, observational study.

BACKGROUND: Hereditary Transthyretin Amyloidosis Polyneuropathy is a rare life-threatening neurologic disease that imposes considerable mortality and it is associated with progressive related disabilities. In this study, we aimed to assess the effect of the disease across health-related quality of life dimensions, in both carriers of the mutation and patients, to compare health-related quality of life with general population, as well as to explore health-related quality of life prognostic factors among patients, including disease progression and treatment. METHODS: This study was a multi-institutional, longitudinal, prospective, observational study of hereditary Transthyretin Amyloidosis Polyneuropathy Portuguese adult subjects (621 asymptomatic carriers and 733 symptomatic patients) enrolled in the Transthyretin Amyloidosis Outcomes Survey. Health-related quality of life was captured with the preference-based instrument EQ-5D-3 L. For general population the dataset included all subjects enrolled in a representative national study (n = 1500). Different econometric models were specified; multivariate probit, generalized linear model and generalized estimating equations model; including demographic and clinical covariates. RESULTS: Hereditary Transthyretin Amyloidosis Polyneuropathy patients have their health status severely impaired in all quality of life dimensions and more anxiety/depression problems were found among asymptomatic carriers. No differences on utility were found between carriers and general population (p = 0.209). Among patients, the utility value is estimated to be 0.51 (0.021), a decrement of 0.27 as compared with general population utility. Higher disease duration, advanced disease stage and not receiving treatment are associated with impaired health-related quality of life. No differences were found between genders (p = 0.910) or between late (≥50 years) and early-onset patients (p = 0.254). The utility estimate ranged from 0.63 (0.009) in stage I to 0.01 (0.005) in stage IV. CONCLUSIONS: Hereditary Transthyretin Amyloidosis Polyneuropathy symptoms and progressive associated disabilities substantially decrease patient's health-related quality of life. Clinical strategies focused on health-related quality of life preservation such as close follow-up of asymptomatic carriers, prompt diagnosis and adequate, early treatment would benefit patient's long-term outcomes, slowing the progressive decline in health-related quality of life.

Societal costs and burden of hereditary transthyretin amyloidosis polyneuropathy.

Background: Hereditary transthyretin amyloidosis polyneuropathy (ATTRv-PN) is a rare life-threatening disease that imposes considerable mortality and morbidity associated with increased costs, high social support and productivity losses. This study aims to estimate the societal costs and burden of ATTRv-PN.Methods: A cost-of-illness (COI) and burden of disease model were specified from a societal perspective, using a prevalence-based approach. Direct and indirect costs were included. Healthcare resource use was retrieved from public databases, previous Portuguese studies and the literature. The burden of disease was expressed in terms of disability-adjusted life years (DALYs), as defined by the World Health Organisation.Results: In 2016, the total annual COI of ATTRv-PN in Portugal was 52,502,796€ and the mean cost per patient was 28,152€ (79% direct; 21% indirect costs). Treatments accounted for 52% of total costs, while 0.18% were devoted to disease prevention. A total of 2056 DALYs were lost, 26% due to disability and 74% due to death.Conclusions: Annual costs and burden of ATTRv-PN were considerable but within the range of other rare diseases. Policies and public interventions to prevent and reduce the burden of disease should be prioritised, since patients experience excess morbidity, mortality and total costs will likely increase in the future.

Cost-effectiveness of the 13-valent pneumococcal conjugate vaccine in adults in Portugal versus "no vaccination" and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine.

The burden of pneumococcal disease in adults is substantial from a social and economic point of view. This study assessed the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults versus "no vaccination" and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A Markov model was used to simulate three strategies: no vaccination, complete vaccination with PPSV23 and complete vaccination with PCV13. The comparison between strategies allowed the estimation of clinical and economic outcomes including incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR). The model took into account the distributions of age, risk profile, vaccination status, type of immunization and time since vaccination in the population. A societal perspective was adopted and a lifetime horizon was considered. Different sources of data and assumptions were used to calibrate PPSV23 and PCV13 effectiveness. Inpatient costs were based on the 2013 diagnosis-related group (DRG) database for National Health Service (NHS) hospitals and expert opinion; NHS official tariffs were the main source for unitary costs. PCV13 shows ICURs of €17,746/QALY and €13,146/QALY versus "no vaccination" and vaccination with PPSV23, respectively. Results proved to be robust in univariate sensitivity analyses, where all ratios were below a €20,000 threshold, with the exception of the scenario with PCV13 effectiveness halved. In a probabilistic sensitivity analysis, 94% of simulations showed cost-effectiveness ratios lower than €20,000/QALY, in both strategies. It was found that PCV13 is a cost-effective strategy to prevent pneumococcal disease in adults in Portugal.

Natural history and survival in stage 1 Val30Met transthyretin familial amyloid polyneuropathy.

OBJECTIVE: To assess the natural history and treatment effect on survival among patients with transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) stage 1 Val30Met. METHODS: Multi-institutional, hospital-based study of patients with TTR-FAP Val30Met prospectively followed up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx)-treated (n = 957), or tafamidis-treated (n = 432) cohorts. Standardized mortality ratios, Kaplan-Meier, and Cox methods were used to estimate excess mortality, survival, and adjusted hazard ratios (HRs) for all-cause mortality. RESULTS: Disease-modifying treatments decreased TTR-FAP excess mortality from 10 to 4 (standardized mortality ratio 3.92, 95% confidence interval [CI] 2.64-5.59). Median overall survival of untreated and LTx-treated cohorts was 11.61 (95% CI 11.14-11.87) and 24.73 years (95% CI 22.90-27.09), respectively, and was not reached in the tafamidis-treated cohort (maximum follow-up, 10 years). Both disease-modifying treatments improved survival. Among early-onset patients (younger than 50 years of age), tafamidis reduced the mortality risk compared with untreated patients by 91% (HR 0.09, 95% CI 0.03-0.25, p < 0.001) and with LTx-treated patients by 63% (HR 0.37, 95% CI 0.14-1.00, p = 0.050). Previous tafamidis treatment did not affect mortality risk after LTx (HR 0.83, 95% CI 0.25-2.78, p = 0.763). Among late-onset patients (50 years and older), tafamidis reduced mortality risk by 82% compared with untreated patients (HR 0.18, 95% CI 0.06-0.49, p = 0.001). CONCLUSION: LTx and tafamidis convey substantial survival benefits, but TTR-FAP mortality remains higher than in the general population. These results strongly reinforce the importance of timely diagnosis and earlier treatment, boosting the pursuit for an increased life expectancy. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with stage 1 Val30Met TTR-FAP, LTx and tafamidis increase survival.

Epidemiology of Transthyretin Familial Amyloid Polyneuropathy in Portugal: A Nationwide Study.

BACKGROUND: Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a rare, hereditary, progressive and neurodegenerative disease. We aimed to study -TTR-FAP epidemiology in Portugal. METHODS: National, observational, prospective and retrospective, case identification of adults with TTR-FAP. Countrywide patient multiple identification sources included reference centers registries and centralized medical electronic prescription database. Crude rates were reported per 100,000 adult inhabitants. RESULTS: Over 2010-2016 period, mean incidence rates was 0.87/100,000 (95% CI 0.68-1.10) corresponding to 71 new patients yearly, that has decreased 31% in the last 7 years. The proportion of late-onset cases (age ≥50 years) among incident cases was 28.7%. Estimated crude 2016 prevalence was 22.93/100,000 adult inhabitants (95% CI 21.90-23.99) corresponding to 1,865 TTR-FAP individuals in Portugal (45.8% male; mean age: 52.3 ± 15.4 years). In 2016, the Portuguese region with the highest TTR-FAP prevalence shows a 16% prevalence increase over the last 25 years. CONCLUSIONS: In Portugal, TTR-FAP affects both genders and mainly young adults. TTR-FAP incidence appears to be decreasing while prevalence is increasing. In comparison to previous studies, there is an increased representativeness of late-onset patients. This epidemiological setting poses future and complex challenges for the social and healthcare system, strengthening the relevance of regular epidemiologic surveillance.

Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for atrial fibrillation in Portugal.

INTRODUCTION AND OBJECTIVES: Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. METHODS: A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). RESULTS: Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. CONCLUSIONS: Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.

A cost-utility analysis of pregabalin versus venlafaxine XR in the treatment of generalized anxiety disorder in Portugal.

BACKGROUND: Generalized anxiety disorder is characterized by excessive anxiety and worry about several events and activities. The estimated 1-year prevalence for adults is around 2% and the lifetime prevalence could reach more than 6%. The disease is associated with reduced quality of life, being comparable to that of major depressive disorder and to chronic illnesses such as diabetes and arthritis, and high consumption of health care resources. METHODS: A previously published patient-level simulation cost-utility model was adapted to the Portuguese context in order to evaluate clinical and economic consequences of using pregabalin in place of venlafaxine XR in the treatment of generalized anxiety disorder. The model predicts the evolution of 1,000 patients with generalized anxiety disorder, simulating their pathway in weekly cycles over one year treatment. This is done by setting a pre-treatment Hamilton Anxiety Scale score and projecting the weekly impact of the pharmacotherapy on this score. The model uses clinical data from an 8-week flexible dose direct comparison clinical trial between the two drugs; utility values based on a Spanish study; and Portuguese economic data, being the resource consumption obtained via an expert panel. RESULTS: Pregabalin patients benefited from 0.738 quality adjusted life years while those on venlafaxine XR achieved 0.712. Moreover, the number of weeks with no or minimal anxiety symptoms was estimated to be 12.9 for pregabalin and only 3.8 for venlafaxine XR. Those clinical gains were achieved at the expense of an extra 715€ per patient, implying an incremental cost per quality adjusted life year of 27,199€ and an incremental cost per week with no or minimal symptoms of 79€. Sensitivity analysis shows that results are robust to main assumptions. CONCLUSIONS: Assuming a threshold of 30,000€ per quality adjusted life year, pregabalin is cost-effective in comparison with venlafaxine XR in the treatment of generalized anxiety disorder in Portugal.

An economic evaluation based on a randomized placebo-controlled trial of varenicline in smokers with cardiovascular disease: results for Belgium, Spain, Portugal, and Italy.

BACKGROUND: An estimated 17.2% of patients continue to smoke following diagnosis of cardiovascular disease (CVD). To reduce the risk of further morbidity or mortality in cardiovascular patients, smoking cessation has been shown to reduce the risk of mortality by 36% and myocardial infarction by 32%. The objective of this study was to evaluate the long-term health and economic consequences of smoking cessation in patients with CVD. DESIGN AND METHODS: Results of a randomized clinical trial comparing varenicline plus counselling vs. placebo plus counselling were extrapolated using a Markov model to simulate the lifetime costs and health consequences of smoking cessation in patients with stable CVD. For the base case, we considered a payer's perspective including direct costs attributed to the healthcare provider, measuring cumulative life years (LY) and quality adjusted life (QALY) years as outcome measures. Secondary analyses were conducted from a societal perspective, evaluating lost productivity due to premature mortality. Sensitivity and subgroup analyses were also undertaken. Results were analysed for Belgium, Spain, Portugal, and Italy. RESULTS: Varenicline plus counselling was associated with a gain in LY and QALY across all countries; relative to placebo plus counselling. From a payer's perspective, incremental cost effectiveness ratios were € 6120 (Belgium), € 5151 (Spain), € 5357 (Portugal), and € 5433 (Italy) per QALY gained. From a societal perspective, varenicline in addition to counselling was less costly than placebo and counselling in all cases. Sensitivity analyses showed little sensitivity in outcomes to model assumptions or uncertainty in model parameters. CONCLUSIONS: Varenicline in addition to counselling is cost-effective compared to placebo and counselling in smokers with CVD.

[Probabilistic cost-effectiveness analysis of oral eletriptan in the treatment of acute migraine in Portugal]. / Análise probabilística de custo-efectividade: utilização do eletriptano no tratamento das crises de enxaqueca em Portugal.

This article explores the application of cost-effectiveness analyses to the use of triptanes (5-HT1 Serotonin agonist) in the pharmacologic treatment of migraine, on the primary and secondary health care, in Portugal. The cost-effectiveness of oral eletriptan (40 and 80 mg) is compared to two matrices defined by the consumption of naratriptan (2.5 mg), sumatriptan (50 and 100 mg) and zolmitriptan (2.5 and 5 mg). The effectiveness vector was calculated based on the time without incapacity caused by migraine. The costs reflect the society perspective. We concluded that the utilization of eletriptan allows health gains with cost reduction in the treatment of migraine, and thereby can be considered a cost-effective alternative to the other oral triptans co-financed by the Portuguese National Health Service.