Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands

OBJECTIVE: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands. METHODS: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens. RESULTS: With voriconazole, the mean cost for treating invasive aspergillosis per patient was E32 651 (2.5th percentile and 97.5th of uncertainty distribution: E30 037; E36 859), compared to E33 616 (E30 920; E39 633) for conventional amphotericin B and E29 115 (E23 537; E61 414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was E150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%. CONCLUSION: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.     

Invasive aspergillosis in pediatric patients

Abstract

This case-based review examines the growing literature on critical issues related to the epidemiology, diagnosis, and treatment of pediatric invasive aspergillosis. Immunocompromised children are at heightened risk for invasive aspergillosis. Children at highest risk include those with new-onset or relapsed hematologic malignancy and recipients of allogeneic stem cell transplants. Additional risk factors in stem cell transplant recipients include impaired lymphocyte engraftment and graft-versus-host disease. Pediatric invasive aspergillosis is associated with a high mortality rate (generally >50%) and requires prompt diagnosis and treatment to prevent dissemination and death. Tools available for diagnosis include radiologic examinations (primarily computed tomography), the galactomannan assay, bronchoalveolar lavage, and tissue biopsy. Age-related differences in computed tomography and galactomannan assay results have been suggested. Recommended primary therapy for pediatric invasive aspergillosis is voriconazole (7?mg/kg IV q12 hours). Currently approved alternative therapies include liposomal amphotericin B, amphotericin B lipid complex, and caspofungin. Posaconazole and itraconazole are also possibilities, but there is no established pediatric dose for posaconazole, and itraconazole dosing is difficult in children. In patients who do not benefit from initial antifungal therapy, options include switching to another agent with a different mechanism of action or combination therapy. Further research is required to better establish optimal approaches to the management of pediatric patients with invasive aspergillosis recalcitrant to initial primary therapy.     

symbol: see text]Caspofungin and [symbol: see text]voriconazole for fungal infections

Systemic fungal infections are difficult to treat and often fatal. Established treatment options include conventional amphotericin B or one of its lipid-based or liposomal formulations, or a triazole antifungal such as fluconazole or itraconazole. [symbol: see text]Caspofungin (Cancidas--Merck Sharp & Dohme) and [symbol: see text]voriconazole (Vfend--Pfizer) are two new antifungals for severe infections caused by Candida spp. (invasive candidiasis) and Aspergillus spp. (invasive aspergillosis). Caspofungin is the first licensed echinocandin antifungal, while voriconazole is a triazole. Promotional claims for caspofungin include that it "provides an effective, yet less toxic, alternative to amphotericin B" while voriconazole is claimed to offer "significantly improved survival in invasive aspergillosis compared with amphotericin B". Here we consider the place of caspofungin and voriconazole in managing patients with severe fungal infections.     

Comparative cost-effectiveness of voriconazole and amphotericin B in treatment of invasive pulmonary aspergillosis.

PURPOSE: The comparative cost-effectiveness of voriconazole and amphotericin B in the treatment of invasive pulmonary aspergillosis (IPA) was examined. METHODS: A decision-tree model was constructed comparing 12-week treatment outcomes in a subset of patients enrolled in a clinical trial comparing initial treatment of IPA with amphotericin B versus voriconazole. Patients included those with IPA who underwent a thoracic computed tomographic (CT) scan at baseline. Cost and survival were estimated for those with and without a halo sign at baseline. Incremental cost-effectiveness ratios comparing voriconazole with amphotericin B were calculated for both patient subgroups. RESULTS: Patients with a halo sign had similar costs and better survival rates than those without the sign. Within the subgroup of patients with the sign, total costs were lower and survival rates higher for those treated with voriconazole than for those treated with amphotericin B. For patients without a halo sign, total costs and survival rates were higher for those treated with voriconazole versus amphotericin B. CONCLUSION: Among patients treated for IPA, those with a baseline CT halo sign, an early indicator of the condition, appeared to have better survival rates and lower health care costs compared with patients without the sign. In patients with the halo sign, survival rates were higher and costs were lower when voriconazole rather than amphotericin B was used as first-line treatment; survival was better with voriconazole than with amphotericin B when the halo sign was not present. Voriconazole was cost-effective compared with amphotericin B when the halo sign was present, but voriconazole's cost-effectiveness when the sign was not present depended on the cost per life saved.     

Current strategies in the treatment of invasive Aspergillus infections in immunocompromised patients.

Aspergillus infections have a very high mortality rate. Their incidence is growing because of the increasing number of immunocompromised patients. Treatment of Aspergillus infection is difficult, and the agents used have numerous adverse effects and toxicities. Recently, new and less nephrotoxic formulations of amphotericin B have come onto the market and other new drugs, such as voriconazole and terbinafine, are under evaluation for this infection. Restoration of host immune defences by tapering of immunosuppressive therapy in transplant patients or correction of granulocytopenia in haematological disease is the cornerstone of modern treatment of aspergillosis in immunocompromised patients. In patients with invasive aspergillosis it is very important to achieve therapeutic concentrations of antimycotic drugs as quickly as possible. Patients at high risk of developing aspergillosis (e.g. those with granulocytopenia) should be treated on the basis of clinical or radiological criteria alone if microbiological or histological diagnosis would significantly delay treatment. Conventional amphotericin B is still the first-line treatment for patients with invasive aspergillosis. In transplant patients receiving other nephrotoxic drugs, particularly cyclosporin, first-line therapy with one of the new amphotericin B formulations should be considered. If the emergence of renal toxicity in any patient precludes aggressive treatment, the patient should be switched to one of the new formulations of amphotericin B. For patients cured with amphotericin B, secondary prophylaxis is needed at the end of the intravenous therapy. Amphotericin B by aerosol or itraconazole are possible solutions. In non-invasive forms of aspergillosis, such as suppurative bronchitis, patients could be treated either with amphotericin B or itraconazole as first-line therapy.     

Cost-effectiveness of statins in the prevention of coronary heart disease events in middle-aged Finnish men

ABSTRACT

Objective: This study evaluated the long-term cost-effectiveness of atorvastatin 20?mg, rosuvastatin 10?mg and simvastatin 40?mg in primary and secondary prevention of CHD in Finland.

Research design and methods: The effect of statin therapy on the incidence of CHD and the expected total costs of the disease were described using a Markov state transition model. Due to the limited amount of evidence concerning mortality and morbidity for rosuvastatin, the model was used to transmute the efficiency data of all statins (decrease in total cholesterol) into long-term endpoints (myocardial infarction, death) using risk functions of the FINRISK and 4S studies. The study followed a characterized cohort of 55-year-old Finnish men with an average 3.3–6.6?%?baseline risk of dying from cardiovascular disease within a 10-year period.

Main outcome measures: Incremental cost-effectiveness ratios (ICERs) for atorvastatin and rosuvastatin, compared with simvastatin, measured as cost of life years gained (€/LYG) and cost of quality adjusted life years gained (€/QALY).

Results: The use of rosuvastatin increased the life expectancy by 0.27 years on average (LYG) compared with simvastatin, producing additional 0.08 quality-adjusted life-years (QALYs). Compared with simvastatin, the cost of one LYG with rosuvastatin was €10 834 and the cost of one QALY gained was €36 548 (discount rate 5?%?per annum). Corresponding figures for atorvastatin were €31 286/LYG and €105 599/QALY.

Conclusions: If the decision makers’ willingness to pay for a QALY gained is around €40 000 there is a high probability (?>?50?%?) that rosuvastatin represents a cost-effective form of therapy in the prevention of CHD in middle-aged men with an average 3.3–6.6?%?risk of dying within 10 years from cardiovascular disease. However, the true clinical impact of these results needs confirmation from on-going clinical trials, as the role of rosuvastatin in reducing clinical events is pending, but for simvastatin and atorvastatin established.     

Voriconazole: in the treatment of invasive aspergillosis

Voriconazole, a broad-spectrum triazole antifungal agent, inhibits the cytochrome P450-dependent enzyme 14-alpha-sterol demethylase, thereby disrupting the fungal membrane and stopping fungal growth. The drug shows excellent in vitro activity against Aspergillus spp., including itraconazole- and amphotericin B-resistant A. fumigatus isolates. At 12 weeks, 52.8% of voriconazole recipients achieved a successful outcome (complete or partial response) versus 31.6% of amphotericin B recipients in a randomised, nonblind trial in 392 patients (aged > or =12 years) with invasive aspergillosis. Patients received intravenous voriconazole (6 mg/kg once every 12 hours on day 1, then 4 mg/kg once every 12 hours for > or =7 days; patients could then be switched to oral voriconazole 200mg once every 12 hours) or intravenous amphotericin B (1 to 1.5 mg/kg/day for > or=14 days). At the investigators' discretion, those who failed to respond to or experienced toxicity with the initial randomised drug could be switched to other licensed antifungal therapy. Voriconazole was generally well tolerated. The most common treatment-related adverse events were transient visual disturbances (approximately 30% of patients) and skin rashes (6%). Voriconazole was generally better tolerated than amphotericin B; voriconazole recipients experienced significantly (p < 0.02 both comparisons) fewer treatment-related adverse events or serious adverse events. The incidence of visual disturbances was significantly (p < 0.001) higher with voriconazole than amphotericin B treatment.     

Cost-effectiveness analysis of pregabalin versus gabapentin in the management of neuropathic pain due to diabetic polyneuropathy or post-herpetic neuralgia

ABSTRACT

Objective: To estimate the cost-effectiveness of branded pregabalin (PGB) versus generic gabapentin (GBP) in patients with neuropathic pain (NeP) due to painful diabetic polyneuropathy (DPN) or post-herpetic neuralgia (PHN) in Spain.

Methods: Using stochastic simulation, we estimated the cost-effectiveness of PGB 150–600?mg/d vs. GBP 900–3600?mg/d in a hypothetical cohort of 1000 patients. The model used data from three randomized controlled clinical trials. Pain was evaluated using a 0–10 scale. Mean baseline pain was 6.9 in both treatment groups. The model assigned untreated pain scores over 84 days. Treated scores were calculated using weekly changes in pain scores from trials. Outcomes included the numbers of days with no or mild pain (score < 4), days with ≥ 30% and ≥ 50% reductions in pain intensity, quality-adjusted life-years (QALYs), and estimated health costs.

Results: Compared with GBP, PGB yielded an estimated mean of 8 (standard error, 0.4) additional days with no or mild pain, 6 (0.4) days with ≥ 30% reduction in pain intensity, 9 (0.5) days with ≥ 50% reduction in pain intensity, and a gain of 0.1186 (0.0002) QALYs for 12 weeks. The estimated total health costs of therapies were €1049 (€35) for PGB and €951 (€38) for GBP, respectively. Incremental cost-effectiveness ratio (ICER) for PGB versus GBP were a mean of €12 (95% confidence interval, €1–24) per additional day with no or mild pain, €431 (dominant–€876) per additional patient with no or mild pain, and €20?535 (€1607–40?345) per QALY gained.

Conclusions: According with data used in this modeling in patients with NeP due to DPN and/or PHN, PGB was shown to be more cost-effective than generic gabapentin in Spain.     

Treatment of drug-resistant Aspergillus infection

Triazole antifungals are frontline drugs for the treatment and prophylaxis of infections due to Aspergillus species. Azole resistance is an emerging problem and is associated with treatment failure in several case series. The management of azole-resistant invasive aspergillosis remains a challenge and there are no guidelines with appropriate recommendations. The current clinical practice suggests that liposomal amphotericin B or a combination of voriconazole or posaconazole with an echinocandin may be effective. Although cross-resistance within the azoles seems to be common, the role of azoles in the management of azole-resistant aspergillosis remains unclear, but optimizing drug exposure is critical for treatment success.     

伏立康唑与伊曲康唑治疗慢性阻塞性肺疾病合并肺曲霉菌感染的循证药物经济学评价

目的： 通过Meta分析评价伏立康唑与伊曲康唑治疗慢性阻塞性肺疾病合并肺曲霉菌感染的安全性、有效性和经济性。方法： 计算机检索中国知网（CNKI）、万方数据库、维普数据库等中文数据库和PubMed、EMbase、Cochrane Library等英文数据库,检索伏立康唑与伊曲康唑治疗慢性阻塞性肺疾病合并肺曲霉菌感染的临床对照试验,使用RevMan5.3软件进行Meta分析,采用成本-效果分析方法进行经济学评价,并进行单因素敏感性分析和概率敏感性分析。结果： Meta分析结果显示,在疗效方面,伏立康唑优于伊曲康唑（OR=3.40,95%CI：2.22~5.21,P<0.01）,在安全性方面,2种方案无显著性差异（OR=0.86,95%CI：0.40~1.84,P=0.70）,均具有较好的安全性。药物经济学评价结果显示,相比于伊曲康唑,伏立康唑治疗的增量成本效果比（ICER）值为45 928.35元,敏感性分析结果与基本分析结果基本一致,说明基础分析结果较为稳定。结论： 伏立康唑治疗慢性阻塞性肺疾病合并肺曲霉菌感染的疗效优于伊曲康唑,但伏立康唑治疗的ICER值过高,因此伊曲康唑治疗慢性阻塞性肺疾病合并肺曲霉菌感染更具有经济性。     

Systematic review and network meta-analysis of clinical outcomes associated with isavuconazole versus relevant comparators for patients with invasive aspergillosis

Objectives: Voriconazole, amphotericin B (AmB) formulations, and isavuconazole are all included in guideline recommendations for treatment of patients with invasive aspergillosis (IA) but the relative efficacy of isavuconazole versus AmB formulations has not been directly compared. We aimed to estimate the relative efficacy of isavuconazole compared with AmB deoxycholate (AmB-D), liposomal AmB (L-AmB), and voriconazole for the treatment of patients with proven/probable IA.

Methods: Nine literature databases were screened for randomized controlled trials comparing treatments with any of voriconazole, AmB-D, L-AmB and isavuconazole for treatment of proven/probable IA. Articles meeting the criteria were included in a meta-analysis to determine the efficacy of AmB-D, L-AmB and voriconazole relative to isavuconazole based on all-cause mortality (ACM) and overall response using a fixed-effects model.

Results: Four articles were identified that compared L-AmB with AmB-D (Study 1), standard-dose L-AmB (3–5?mg/kg/day) with high-dose L-AmB (10?mg/kg/day; Study 2), voriconazole with AmB-D (Study 3), and isavuconazole with voriconazole (Study 4). In the network meta-analysis, isavuconazole was statistically superior to AmB-D on both ACM (odds ratio [95% credible intervals] shown as natural log, 1.00 [0.26, 1.74]) and overall response (?1.39 [?2.21, ?0.63]). Differences between isavuconazole, and standard-dose L-AmB, high-dose L-AmB and voriconazole were not statistically significant for either ACM (0.18 [?1.17, 1.53], 0.50 [?1.11, 2.13] and 0.32 [?0.19, 0.84], respectively) or overall response (?0.99 [?2.21, 0.29], ?0.89 [?2.41, 0.65] and 0.06 [?0.43, 0.57], respectively).

Conclusions: This data suggests that the efficacy of isavuconazole for treatment of IA is superior to AmB-D and comparable with both L-AmB and voriconazole.     

Cost-effectiveness in Italy of preventive treatment with ramipril in patients at high risk of cardiovascular events

ABSTRACT

Objectives: A cost-effectiveness analysis was conducted in Italy of preventive treatment with ramipril (an angiotensin converting enzyme [ACE] inhibitor) compared to no treatment in patients at high risk of cardiovascular death. The analysis was based on data extracted from the HOPE trial.

Methods: The current life table method was used in order to model a lifetime time horizon for outcomes and costs. The cohorts used were 1000 subjects on ramipril, and 1000 subjects on placebo enrolled in the HOPE trial. Kaplan–Meier curves at 5 years of the clinical study were fitted using an exponential model over a lifetime horizon, the outcome variables being myocardial infarction, stroke, revascularization and death. Total direct medical costs have been considered from a third-party payer's perspective – the Italian National Health Service. Resources involved in each event/activity were estimated using the modified Delphi technique with a panel of six clinicians. Types of resources reported included drug therapies, laboratory and imaging tests, physician visits, outpatient and inpatient rehabilitation, as well as medical and surgical hospital admissions. The incremental cost per life year gained was the main measure of the analysis.

Results: ICER (incremental cost-effectiveness ratio) decreases with the length of the treatment period. After the first year the ICER is €55?062 and subsequently decreases to about €12?770 at 5 years, €5945 at 10 years and €3726 at 20 years. The two ways sensitivity analysis showed that at 5 years ICERs range from a saving of €4059 to a cost of €22?929 (at 20 years they are €1814 and €4434), mainly depending on the cost of drug and cost of events. Previous analyses in other countries based on the HOPE study obtained ICER values which are comparable with our results, when taking into account the different cost structure of the health care systems.

Conclusions: On the basis of these results, the use of ramipril is likely to represent an efficient use of public health expenditure in the Italian healthcare system.     

Echinocandins: role in antifungal therapy, 2005

Novel therapies to treat invasive fungal infections have revolutionised the care of patients with candidiasis, aspergillosis and other less common fungal infections. Physicians in the twenty first century have access to safer versions of conventional drugs (i.e., lipid amphotericin B products), extended-spectrum versions of established drugs (i.e., voriconazole), as well as a new class of antifungal agents; the echinocandins. The increased number of options in the antifungal armamentarium is well timed, as the incidence of both invasive candidiasis and invasive aspergillosis, and the financial burden associated with these infections, have increased significantly in the past several decades. The increasing incidence of fungal infections has risen in parallel with the increase in critically ill and immunocompromised patients. Candida is the fourth most common bloodstream isolate, approximately 50% of which are non-albicans species. Estimates suggest there to be 9.8 episodes of invasive candidiasis per 1000 admissions to surgical intensive care units, with attributable mortality at 30% and cost per episode of US44,000 dollars. The burden of candidiasis is even higher in the paediatric population, with Candida being the second most common bloodstream infection. The increase in non-albicans candidiasis mandates the introduction of new antifungal agents capable of treating these often azole-resistant isolates. In addition, there has been a rise in the incidence of invasive aspergillosis, the most common invasive mould infection following haematopoietic stem cell transplantation, with an estimated incidence of 10 - 20%. The mortality associated with invasive aspergillosis has increased by 357% since 1980. Unfortunately, the overall survival rate among patients treated with amphotericin B, and even voriconazole, remains suboptimal, as evidenced by the failure of treatment in 47% of patients in the landmark voriconazole versus amphotericin B trial. Given the increasing incidence and suboptimal outcomes of these serious fungal infections, novel therapies represent an opportunity for significant advancement in clinical care. The current challenge is to discover the optimal place for the echinocandins in the treatment of invasive fungal infections.     

The economic value of anti-IgE in severe persistent,IgE-mediated (allergic) asthma patients:adaptation of INNOVATE to Sweden

ABSTRACT

Background: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma.

Methods: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an ‘optimized asthma control’ state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time.

Results: Total lifetime discounted costs and QALYs on ST were €52?702 and 11.60. Omalizumab add-on therapy cost an additional €42?754 for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of €56?091. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [€31?328; €120?552]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates.

Conclusions: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.     

Caspofungin: new preparation. A last resort in invasive aspergillosis

(1) Invasive aspergillosis is rare. It usually occurs in immunocompromised patients and is fatal despite treatment in 40-90% of cases. The reference treatments are standard amphotericin B, liposomal amphotericin B, and itraconazole. (2) Caspofungin, an antifungal drug, is now approved in the Europe Union for the treatment of invasive aspergillosis, when reference drugs fail or are poorly tolerated. (3) In a non comparative trial in 69 patients, intravenous caspofungin infusion was at least partly effective: 40% of patients survived with few relapses for at least one year following treatment. A historical comparison also favours caspofungin therapy. (4) The safety profile of caspofungin is poorly documented. It includes local reactions at the injection site, systemic reactions linked to the infusion (especially due to histamine release) and hepatic disorders. (5) Caspofungin is known to interact with tacrolimus (lower tacrolimus concentrations), ciclosporin (increased caspofungin bioavailability) and rifampicin (reduced caspofungin bioavailability). (6) In practice, caspofungin is an acceptable option for the treatment of invasive aspergillosis when standard amphotericin B, liposomal amphotericin B, and itraconazole are ineffective or poorly tolerated. Its clinical assessment is limited and must be continued.     

Voriconazole: new preparation. Invasive aspergillosis: benefits to be confirmed

(1) Amphotericin B is the antifungal drug of choice for the treatment of invasive aspergillosis, severe candidiasis and Fusarium infection. Voriconazole is an antifungal azole sold in France for oral and intravenous treatment of these infections. (2) In 391 patients with established or probable invasive aspergillosis, combined analysis of two trials comparing voriconazole (intravenously then orally) with conventional amphotericin (intravenously) showed that the 12-week survival rate was significantly higher with voriconazole (70.8% versus 57.9%). Unfortunately, these results are undermined by methodological flaws such as the lack of blinding, the very different intravenous treatment periods in the two groups, and subsequent oral treatment with different antifungal drugs. Voriconazole has not been compared with liposomal amphotericin B. (3) In the treatment of severe candidiasis, and severe Scedosporium and Fusarium infections, we only have the (favourable) results of non comparative trials in small numbers of patients refractory to other antifungal drugs. (4) The main adverse effects were visual disturbances, elevated hepatic enzyme levels, acute renal failure, and sometimes serious cutaneous reactions. It lengthens the QT interval and can cause torsades de pointes. It inhibits the cytochrome P450 isoenzymes CY3A4, CYP2C9 and CYP2C19, hence a high risk of potentially serious drug interactions. (5) Voriconazole can be given by mouth or by IV infusion, whereas liposomal amphotericin B must be given intravenously. (6) In practice, another more rigorous trial is needed to confirm the favourable results obtained with voriconazole in invasive aspergillosis. Voriconazole is the first-line treatment for severe Scedosporium infections, despite limited experience. It is a last resort for severe candidiasis and severe Fusarium infection.     

A cost-effectiveness model of smoking cessation based on a randomised controlled trial of varenicline versus placebo in patients with chronic obstructive pulmonary disease

Objectives: Smoking is an important risk factor in chronic obstructive pulmonary disease (COPD). A recent clinical trial demonstrated the efficacy of varenicline versus placebo as an aid to smoking cessation in patients with COPD. This study examines the cost-effectiveness of varenicline from the perspective of the healthcare systems of Spain (base case), the UK, France, Germany, Greece and Italy.

Methods: A Markov model was developed to determine the cost-effectiveness of varenicline as an aid to smoking cessation, compared to a placebo, in a COPD population. Cost-effectiveness was determined by the incremental cost per quality-adjusted life year (QALY) gained.

Results: In the Spanish base case varenicline had an incremental cost of €1021/person for an average of 0.24 life years (0.17 QALYs), gained over the lifetime of a cohort of COPD patients, resulting in an incremental cost-effectiveness ratio (ICER) of €5,566. In the other European countries, the ICER varied between €4,519 (UK) and €10,167 (Italy). Probabilistic sensitivity analysis suggested varenicline had a high probability (>95%) of being cost-effective at a threshold of €30,000/QALY.

Conclusions: Varenicline is expected to be a cost-effective aid to smoking cessation in COPD patients in all of the countries studied.     

Current antifungal treatment of fusariosis

Fungi of the genus Fusarium are well known as major plant pathogens and soil inhabitants, but also cause a broad spectrum of human infections. Fusariosis is the second most common mould infection after aspergillosis, and keratitis is the most encountered implantation infection in immunocompetent individuals. Natamycin is active against Fusarium species both in vitro and in vivo, and is used along with voriconazole as the mainstay of treatment for Fusarium keratitis. Onychomycosis is treated with terbinafine, voriconazole and sometimes itraconazole. Cure is possible despite high in vitro minimum inhibitory concentrations (MICs). Recently, disseminated infections have increased dramatically, mainly affecting severely immunocompromised patients. The remarkable intrinsic resistance of Fusarium species to most antifungal agents results in high mortality rates in this patient population. Recovery of neutropenia is essential for patient survival and treatment should include voriconazole or amphotericin B as first–line and posaconazole as salvage therapy.     

伏立康唑治疗侵袭性真菌感染有效性及安全性的Meta分析

目的系统评价伏立康唑治疗侵袭性真菌感染的有效性及安全性。方法检索PubMed、Co-chrane Library、EMbase、CNKI、CBM、VIP数据库,收集截至2011年12月已发表的伏立康唑治疗深部真菌感染的随机对照试验。由2名研究者按照纳入标准独立筛选文献、提取资料和评价质量后,采取RevMan 5.0软件进行Meta分析。结果共纳入研究7项,676例。Meta分析结果提示,伏立康唑、两性霉素B的治疗成功率比较,差异无统计学意义;伏立康唑、伊曲康唑的治疗成功率、不良反应发生率比较,差异均无统计学意义;伏立康唑治疗成功率略高于米卡芬净组(P=0.11),但差异无统计学意义,其不良反应发生率高于米卡芬净(P=0.000 6)。结论伏立康唑在治疗侵袭性真菌感染中表现出高效低毒的特点。随着其临床应用愈加广泛,其价值有待进一步检验。     

Voriconazole therapeutic drug monitoring: focus on safety

Importance of the field: Voriconazole has been widely used for the treatment of invasive fungal diseases, particularly invasive aspergillosis. Drug–drug interactions are, however, the main drawback associated with voriconazole use, since this drug suffers from extensive hepatic metabolism.

Areas covered in this review: This article reviews the current literature on voriconazole therapeutic drug monitoring, with a special focus on drug safety.

What the reader will gain: An update on voriconazole metabolism, drug interactions, toxicity and the relation of these with voriconazole drug concentrations.

Take home message: Therapy with voriconazole may be better guided by measuring voriconazole concentrations in the plasma.