Pharmacological Acromegaly Treatment: Cost-Utility and Value of Information Analysis.

OBJECTIVES: To conduct a cost-utility analysis comparing drug strategies involving octreotide, lanreotide, pasireotide, and pegvisomant for the treatment of patients with acromegaly who have failed surgery, from a Brazilian public payer perspective. METHODS: A probabilistic cohort Markov model was developed. One-year cycles were employed. The patients started at 45 years of age and were followed lifelong. Costs, efficacy, and quality of life parameters were retrieved from the literature. A discount rate (5%) was applied to both costs and efficacy. The results were reported as costs per quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated when applicable. Scenario analyses considered alternative dosages, discount rate, tax exemption, and continued use of treatment despite lack of response. Value of information (VOI) analysis was conducted to explore uncertainty and to estimate the costs to be spent in future research. RESULTS: Only lanreotide showed an ICER reasonable for having its use considered in clinical practice (R$ 112,138/US$ 28,389 per QALY compared to no treatment). Scenario analyses corroborated the base-case result. VOI analysis showed that much uncertainty surrounds the parameters, and future clinical research should cost less than R$ 43,230,000/US$ 10,944,304 per year. VOI also showed that almost all uncertainty that precludes an optimal strategy choice involves quality of life. CONCLUSIONS: With current information, the only strategy that can be considered cost-effective in Brazil is lanreotide treatment. No second-line treatment is recommended. Significant uncertainty of parameters impairs optimal decision-making, and this conclusion can be generalized to other countries. Future research should focus on acquiring utility data.

Cost-Effectiveness of Initial Versus Delayed Lanreotide for Treatment of Metastatic Enteropancreatic Neuroendocrine Tumors.

BACKGROUND: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. METHODS: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide's cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. RESULTS: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide's price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. CONCLUSIONS: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.

New sustainable alternatives to reduce the production costs for surfactin 50 years after the discovery.

In 1968, Arima et al. discovered the heptapeptide, known as surfactin, which belongs to a family of lipopeptides. Known for its ability to reduce surface tension, it also has biological activities such as antimicrobial and antiviral. Its non-ribosomal synthesis mechanism was later discovered (1991). Lipopeptides represent an important class of surfactants, which can be applied in many industrial sectors such as food, pharmaceutical, agrochemicals, detergents, and cleaning products. Currently, 75% of the surfactants used in the various industrial sectors are from the petrochemical industry. Nevertheless, there are global current demands (green chemistry concept) to replace the petrochemical products with environmentally friendly products, such as surfactants by biosurfactants. The production biosurfactants still are costly. Thus, an alternative to reduce the production costs is using agro-industrial waste as a culture medium associated with an efficient and scalable purification process. This review puts a light on the agro-industrial residues used to produce surfactin and the techniques used for its recovery.

Production of the natural iron chelator deferriferrichrysin from Aspergillus oryzae and evaluation as a novel food-grade antioxidant.

BACKGROUND: Deferriferrichrysin (Dfcy) is a siderophore found in foods fermented by Aspergillus oryzae and is a promising candidate for an antioxidant food additive because of its high binding constant toward iron. However, the Dfcy concentration is typically low in foods and cultures. RESULTS: We optimised culture conditions to improve Dfcy production to 2800 mg L(-1) from 22.5 mg L(-1) under typical conditions. Then, we evaluated the potential of Dfcy as a food additive by measuring its safety, stability, and antioxidant activity. Dfcy was sufficiently stable that over 90% remained after pasteurisation at 63 °C for 30 min at pH 3-11, or after sterilisation at 120 °C for 4 min at pH 4-6. Dfcy showed high antioxidant activity in an oil-in-water model, where inhibition of lipid oxidation was measured by peroxide value (PV) and thiobarbituric acid reactive substances (TBARS) assays. Dfcy decreased PV and TBARS by 83% and 75%, respectively. Antioxidant activity of Dfcy was equal to or higher than that of the synthetic chelator EDTA. CONCLUSION: Our study provides the first practical method for production of Dfcy. Dfcy can be a novel food-grade antioxidant and the first natural alternative to the synthesised iron chelator EDTA. © 2015 Society of Chemical Industry.

Improvement of surfactin production in Bacillus subtilis using synthetic wastewater by overexpression of specific extracellular signaling peptides, comX and phrC.

Surfactin is a biological surfactant with numerous potential applications. In this study, Bacillus subtilis was engineered to improve surfactin production by the activation of two competence-stimulating pheromones, ComX and competence and sporulation factor (CSF) to stimulate the transcription of srfA operon. Both signaling factors, encoded by comX and phrC, were successfully overexpressed and subsequently increased surfactin production. Surfactin produced by engineered strains showed functional groups similar to the commercially available surfactin analyzed via Fourier transform infrared spectroscopy (FTIR). Surfactin production in the B. subtilis (pHT43-comXphrC) strain was 6.4-fold greater than in the wild strain, with approximately 135.1 mg/L surfactin produced after 48 h cultivation. To reduce the production costs of surfactin, synthetic wastewater was used, from which the B. subtilis (pHT43-comXphrC) strain produced approximately 140.2 mg/L surfactin. The results obtained demonstrated the production of surfactin from synthetic wastewater, which is beneficial in lowering the overall production costs.

Cost-Effectiveness and Efficacy of a Novel Combination Regimen in Acromegaly: A Prospective, Randomized Trial.

CONTEXT: Combination therapy with somatostatin receptor ligand (SRL) plus pegvisomant for patients with acromegaly is recommended after a maximizing dose on monotherapy. Lower-dose combination regimens are not well studied. OBJECTIVE: To compare cost-effectiveness and efficacy of 3 lower-dose combination regimens in controlled and uncontrolled acromegaly. DESIGN AND SETTING: Prospective, randomized, open-label, parallel arm study at a tertiary referral pituitary center. PATIENTS: Adults with acromegaly regardless of response to prior SRL and biochemical control status at baseline, stratified by an SRL dose required for insulin-like growth factor (IGF)-I normalization during any 3-month period within 12 months preceding enrollment. INTERVENTION: Combination therapy for 24 to 32 weeks on arm A, high-dose SRL (lanreotide 120 mg/octreotide long-acting release [LAR] 30 mg) plus weekly pegvisomant (40-160 mg/week); arm B, low-dose SRL (lanreotide 60 mg/octreotide LAR 10 mg) plus weekly pegvisomant; or arm C, low-dose SRL plus daily pegvisomant (15-60 mg/day). MAIN OUTCOME MEASURE: Monthly treatment cost in each arm in participants completing ≥ 24 weeks of therapy. RESULTS: Sixty patients were enrolled and 52 were evaluable. Fifty of 52 (96%) demonstrated IGF-I control regardless of prior SRL responsiveness (arm A, 14/15 [93.3%]; arm B, 22/23 [95.7%]; arm C, 14/14 [100%]). Arm B was least costly (mean, $9837 ±â€…1375 per month), arm C was most expensive (mean, $22543 ±â€…11158 per month), and arm A had an intermediate cost (mean, $14261 ±â€…1645 per month). Approximately 30% of patients required pegvisomant dose uptitration. Rates of adverse events were all < 10%. CONCLUSIONS: Low-dose SRL plus weekly pegvisomant represents a novel dosing option for achieving cost-effective, optimal biochemical control in patients with uncontrolled acromegaly requiring combination therapy.

Synthetic Cross-linking of Peptides: Molecular Linchpins for Peptide Cyclization.

Peptide-derived drugs constitute a significant fraction of therapeutic agents. In 2013, The global market of peptide therapeutics was ca. $19 billion; this value does not include revenue from insulin derivatives of $28 million. The combined sales of insulin and non-insulin peptide drugs is estimated to exceed $70 billion by 2019. A significant fraction of peptide-derived drugs is composed of an amino acid sequence and additional chemical functionalities that improve biological and pharmacological properties of the drug. In this review, we focus on synthetic cross-linkers that we refer to as "linchpins", which are commonly used to constrain the secondary structure of peptides and equip them with added benefits such as resistance to proteolytic degradation and conformational stability. The latter property leads to an increase in binding potency and increased bioavailability due to increased permeation through biological membranes. Some linchpins can even introduce properties not found in natural peptides such as light-responsiveness. Peptides cyclized by linchpins can be viewed as a sub-class of a larger family of peptide-derived drugs with desired pharmacological performance in vivo. To understand how chemical modifications by linchpins improve drug discovery, this review also briefly summarizes canonical examples of chemical modification used in modern peptide therapeutics.

LanroNET - A Non-Interventional Prospective Study to Assess the Resource Utilisation and Cost of Lanreotide Autogel 120 mg in the Population of Polish Patients with Symptomatic Neuroendocrine Tumours.

Wstep: Celem badania LanroNET byla ocena wykorzystania zasobów medycznych oraz kosztów objawowego leczenia polskich chorych na nowotwory neuroendokrynne z zastosowaniem lanreotydu autogel 120 mg. Material i metody: LanroNET to wieloosrodkowe, nieinterwencyjne, obserwacyjne, prospektywne badanie przeprowadzone w 12 osrod-kach w Polsce. W badaniu uczestniczyli dorosli chorzy na wydzielajace nowotwory neuroendokrynne leczeni lanreotydem autogel 120 mg od przynajmniej 3 miesiecy przed wlaczeniem do badania. Podczas 24-miesiecznej obserwacji rzeczywistej praktyki klinicznej zbierano dane dotyczace wykorzystania zasobów medycznych oraz przebiegu terapii chorych z wydzielajacymi nowotworami neuroendokrynnymi. WYNIKI: W badaniu uczestniczylo 54 chorych na wydzielajace nowotwory neuroendokrynne. Przecietny czas stosowania lanreotydu wynosil 1,7 roku (zakres 0,0-2,2 lata). Badanie ukonczylo 33 pacjentów, najczestsza przyczyna przedwczesnego zakonczenia leczenia (8/16) byla progresja choroby. Calkowity sredni koszt wykorzystanych zasobów bez kosztów farmakoterapii oszacowano na 26 307 zl/EUR 6.030,35 na pacjenta/rok. W czasie badania sredni odstep miedzy wstrzyknieciami lanreotydu wynosil 31,7 dni (6,7). Pod koniec obserwacji, po 24 miesiacach od follow-up, 7 pacjentów stosowalo 42-dniowe odstepy miedzy dawkami. Sredni rzeczywisty koszt lanreotydu autogel 120 mg wyniósl 4216,30 zl/966,49 EUR na pacjenta/28 dni we wspólnej perspektywie platnika i pacjenta i byl nizszy o 554,16 zl/127,02 EUR niz koszt stosowania standardowych 28-dniowych odstepów miedzy dawkami. WNIOSKI: Badanie LanroNET jest pierwszym w Polsce obserwacyjnym dwuletnim badaniem chorych na czynne hormonalnie nowotwo-ry neuroendokrynne zoladkowo-jelitowo-trzustkowe oceniajacym koszty codziennej praktyki klinicznej i koszty leczenia lanreotydem autogel.

68 Ga-somatostatin analogue PET-CT: Analysis of costs and benefits in a public hospital setting.

INTRODUCTION: Between 2009 and 2012, 68 Ga-somatostatin analogue PET-CT progressively replaced 111 In-octreotide scintigraphy for imaging neuroendocrine tumours in WA public hospitals due to published literature demonstrating improved diagnostic accuracy and increased availability. Despite significantly improved sensitivity and specificity, 68 Ga-somatostatin analogue PET is currently unfunded in Australia. This study sought to undertake cost analysis of the two modalities in a public hospital setting and to compare them with regard to patient factors such as imaging time and radiation dose. METHODS: This analysis was based on retrospective clinical data from 95 111 In-octreotide scintigraphies performed in 2007 and 2008 at Sir Charles Gairdner (SCGH) and Royal Perth (RPH) hospitals and 219 68 Ga-somatostatin analogue PET-CT studies performed in 2013 at SCGH. Whole body effective radiation dose was derived from the radiopharmaceutical and low-dose CT scan. The cost analysis included radiopharmaceutical and imaging costs. RESULTS: The median imaging time for an 111 In-octreotide scintigraphy was 152 min at SCGH, 100 min at RPH and 20 min for a 68 Ga-somatostatin analogue PET-CT scan. The mean effective radiation dose for 111 In-octreotide scintigraphy was 18.1 mSv at SCGH and 13.8 mSv at RPH. The effective dose for 68 Ga-somatostatin analogue PET-CT was 8.7-10.8 mSv. The average cost of 68 Ga-somatostatin analogue PET-CT was four times less than 111 In-octreotide scintigraphy. CONCLUSION: 68 Ga-somatostatin analogue PET-CT is not only more accurate than 111 In-octreotide scintigraphy, this study has also shown that it is significantly less expensive, delivers a lower radiation dose to patients and requires less imaging time for patients and staff. 68 Ga-somatostatin PET-CT provides an important combination of both reduced cost and improved clinical care for patients.

Micafungin: a new echinocandin antifungal.

The echinocandins represent the newest class of antifungals to combat infections caused by Candida sp. Micafungin is an echinocandin recently approved by the United States Food and Drug Administration. It is indicated in adults for esophageal candidiasis and prophylaxis against candidal infections in hematopoietic stem cell transplant recipients. Micafungin exhibits in vitro fungicidal activity against Candida sp, including fluconazole-resistant isolates. Its in vivo efficacy is comparable to that of fluconazole in the treatment of esophageal candidiasis and superior to that of fluconazole for prophylaxis of invasive candidal infections. Because it is not significantly metabolized by the cytochrome P450 3A system, micafungin is associated with few drug interactions. Micafungin does not require adjustment in patients with renal and/or hepatic impairment, and it has been shown to be well tolerated in both adult and pediatric patients. Its efficacy against Candida sp, coupled with its overall safety and drug interaction profiles, makes it an attractive option in the treatment against esophageal candidiasis and prophylaxis against invasive candidal infections.

Pharmacoeconomic analysis of caspofungin versus liposomal amphotericin B as empirical antifungal therapy for neutropenic fever.

PURPOSE: An analysis was conducted that evaluated and compared the cost differences between caspofungin and liposomal amphotericin B when the medications were used as empirical antifungal therapy for persistent fever during neutropenia. METHODS: Rates of drug use and impaired renal function (IRF) were based on data from published studies. IRF was defined as a doubling of the serum creatinine level or, if the creatinine level was elevated at enrollment, an increase of at least 1 mg/dL. The estimates of the costs for drug acquisition and treating IRF were derived using published data and applied to compare caspofungin with liposomal amphotericin B. Sensitivity analyses were performed by varying the IRF and relative acquisition costs to assess the effect of these factors on the cost differences. RESULTS: The acquisition costs per patient were 6942 dollars for liposomal amphotericin B and 3996 dollars for caspofungin. The estimated cost per patient from IRF was 3173 dollars for liposomal amphotericin B and 793 dollars for caspofungin. Combining drug acquisition and IRF costs, the overall treatment cost per patient for caspofungin was 5326 dollars less than for liposomal amphotericin B. In sensitivity analyses of drug costs, the price of liposomal amphotericin B would have to be 23.95 dollars per vial for the overall treatment costs to be equal. CONCLUSION: Comparison of cost estimates derived from published data revealed that a combined estimate of acquisition costs and costs related to the treatment of IRF was lower for caspofungin than for liposomal amphotericin B for empirically treating patients with neutropenic fever.

Economic evaluation of voriconazole versus caspofungin for the treatment of invasive aspergillosis in Spain.

BACKGROUND AND OBJECTIVE: Invasive fungal infections are becoming increasingly prevalent and are more frequently the aetiological agents responsible for nosocomial infections. Since mid-2002, two new antifungal drugs - voriconazole, a third-generation azole, and caspofungin, a member of a new class of drugs called echinocandins - have been marketed in Spain. Both drugs have proven [corrected] efficacy in the treatment of aspergillosis, are better tolerated than amphotericin B and are cheaper [corrected] than liposomal amphotericin B. The objective of this study was to conduct an economic evaluation of voriconazole versus caspofungin for the treatment of invasive aspergillosis in Spain. METHODS: This was a cost-minimisation analysis (2006 costs) from the hospital perspective. Duration of treatment and bodyweight of patients were obtained from the Fungcost study and the incidence of adverse events was obtained from different published sources. Only direct costs were considered. Mean expected cost and incremental cost were calculated, and univariate and bivariate (bodyweight/treatment duration) sensitivity analyses were conducted. RESULTS: The mean expected cost per episode was 6041.93 euro (intravenous treatment acquisition cost 5524.75 euro) for voriconazole and 7174.05 euro (intravenous treatment acquisition cost 6672.80 euro) for caspofungin in invasive aspergillosis; the incremental cost was 1132.18 euro. Results were robust for any treatment duration and sensitive to bodyweights <103.42 kg. CONCLUSION: Voriconazole is a more cost-effective option than caspofungin in invasive aspergillosis in patients with a bodyweight <103.42 kg.

Cost savings with implementation of PNA FISH testing for identification of Candida albicans in blood cultures.

Antifungal expenditures are substantial for many hospitals. Using caspofungin for the treatment of candidemia accounts for a sizable proportion of the costs. A cost minimization study that used a decision analytic model was done to compare in-hospital diagnosis and treatment costs using the Candida albicans peptide nucleic acid fluorescence in situ hybridization (PNA FISH) test versus the C. albicans screen test for differentiating C. albicans from non-albicans Candida species bloodstream infections. Assuming physician notification of yeast identity concurrent with blood culture positivity, potential savings resulting from use of the C. albicans PNA FISH test compared with the C. albicans screen test averaged $1837 per patient treated, although laboratory costs for doing the C. albicans PNA FISH test ($82.72) exceeded those for the C. albicans screen test ($2.83). Savings were realized through a decrease in antifungal drug costs, particularly caspofungin. Incorporating the C. albicans PNA FISH test as part of the initial identification algorithm for yeasts recovered from blood can result in substantial savings for hospitals.

Empirical anti-Candida therapy among selected patients in the intensive care unit: a cost-effectiveness analysis.

BACKGROUND: Mortality from invasive candidiasis is high. Low culture sensitivity and treatment delay contribute to increased mortality, but nonselective early therapy may result in excess costs and drug resistance. OBJECTIVE: To determine the cost-effectiveness of anti-Candida strategies for high-risk patients in the intensive care unit (ICU). DESIGN: Cost-effectiveness decision model. DATA SOURCES: Published data to 10 May 2005, identified from MEDLINE and Cochrane Library searches, ICU databases, expert estimates, and actual hospital costs. TARGET POPULATION: Patients in the ICU with suspected infection who have not responded to antibacterial therapy. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTIONS: Fluconazole, caspofungin, amphotericin B, or lipid formulation of amphotericin B given as either empirical or culture-based therapy and no anti-Candida therapy. OUTCOME MEASURES: Incremental life expectancy and incremental cost per discounted life-year (DLY) saved. RESULTS OF BASE-CASE ANALYSIS: Ten percent of the target population will have invasive candidiasis. Empirical caspofungin therapy is the most effective strategy but is expensive (295,115 dollars per DLY saved). Empirical fluconazole therapy is the most reasonable strategy (12,593 dollars per DLY saved) and decreases mortality from 44.0% to 30.4% in patients with invasive candidiasis and from 22.4% to 21.0% in the overall target cohort. RESULTS OF SENSITIVITY ANALYSIS: Empirical fluconazole therapy is reasonable for likelihoods of invasive candidiasis greater than 2.5% or fluconazole resistance less than 24.0%. For higher resistance levels, empirical caspofungin therapy is preferred. For low prevalences of invasive candidiasis, culture-based fluconazole is reasonable. For prevalences exceeding 60%, empirical caspofungin therapy is reasonable. For caspofungin to be reasonable at a prevalence of 10%, its cost must be reduced by 58%. LIMITATIONS: Less severe illness and limited use of broad-spectrum antimicrobial agents, typical of smaller hospitals, could result in a lower risk for invasive candidiasis. CONCLUSIONS: In patients in the ICU with suspected infection who have not responded to antibiotic treatment, empirical fluconazole should reduce mortality at an acceptable cost. The use of empirical strategies in low-risk patients is not justified.

Caspofungin versus amphotericin B for candidemia: a pharmacoeconomic analysis.

BACKGROUND: In a randomized, comparative, clinical trial, caspofungin was found to be as effective as amphotericin B deoxycholate (ampho B) for treating candidemia (favorable outcomes in 71.7% and 62.8% of patients, respectively) and exhibited a generally better safety profile, particularly with respect to impaired renal function (IRF) (P = 0.02). OBJECTIVE: The goal of this study was to examine whether cost savings generated from the reduced rates of IRF observed in the clinical trial would be enough to offset the higher acquisition cost of caspofungin relative to ampho B. METHODS: We developed an economic model in which 100 hypothetical patients with candidemia were treated with caspofungin or ampho B. Rates of IRF and duration of drug therapy were taken from the clinical trial. Information on the cost of treating IRF was obtained through a search of MEDLINE using the terms amphotericin and cost, amphotericin and resource, amphotericin and hospital, and amphotericin and toxicity; and the medical subject headings kidney failure, acute/drug therapy; kidney failure, acute/epidemiology; kidney failure, acute/etiology; kidney/drug effects; cost of illness; costs and cost analysis; kidney failure, acute, and economics; and kidney failure, acute/economics. In addition, the Web site was searched for relevant references, and the Merck publication alert system was used. Antifungal drug costs were estimated using data from IMS Health. Costs were reported in year-2003 US dollars. RESULTS: In the base case, the model projected that using caspofungin instead of ampho B would result in substantially lower treatment costs for IRF, which would more than offset the higher drug acquisition cost (cost-offset percentage, 122%), leading to a net mean savings of 758.60 US dollars per patient. These results were not very sensitive to the difference in daily drug cost, but were sensitive to the mean cost attributable to treating IRF. As that varied, the cost-offset percentage varied from 61% (substantial cost offset) to 183% (cost savings). CONCLUSIONS: The results of this economic model suggest that, based only on differences in drug acquisition cost and renal toxicity, the use of caspofungin instead of ampho B in patients with candidemia may be a cost-saving strategy from the perspective of a hospital.

[Economic evaluation of the treatment of systemic fungal infections in immunocompromised patients: the role of itraconazole]. / Aspetti farmacoeconomici del trattamento delle micosi sistemiche profonde in pazienti immunocompromessi: il ruolo di itraconazolo.

In recent years, the incidence of HIV infection, the intensity of chemotherapy regimens for cancer and the use of bone marrow transplantation have all increased. This results in an increase in the incidence of systemic fungal infections, which are associated high rates of morbidity and mortality in this immunosuppressed population; the incidence is growing: 50% for neutropenic/transplant bone marrow patients and 5-20% for organ transplant. Fluconazole, itraconazole, amphotericin-B and, in the recent years, caspofungin and voriconazole are the most frequently used antifungal agents. However, the newly developed formulations of itraconazole and lipid-associated formulations of amphotericin-B have provide new treatment options for systemic fungal infection and have prompted a number of comparisons of the treatment costs of empirical therapy. The i.v. formulation of itraconazole may be more cost effective than either conventional or liposomial formulations of amphotericin-B when used as empirical therapy for neutropenic patients with persistent fever despite broad spectrum antibiotic therapy, but further studies are required. The lack of studies, national and international, and the small amount of available data on the cost of systemic fungal infections mean that the costs saving from prophylactic and empirical use of antifungals are difficult to estimate.

Dosage and costs of lanreotide Autogel 120 mg administered as part of routine acromegaly care in Poland - two years of data from Lanro-Study.

INTRODUCTION: To evaluate, over 24 months of prospective follow-up, the dosage and costs of lanreotide AUTOGEL 120 mg (ATG120) administered as part of routine acromegaly care in Poland. MATERIAL AND METHODS: A multicentre, non-interventional, observational prospective study on resource utilisation in Polish acromegalic patients treated with ATG120 at 4-week or extended (> 4 weeks) dosing interval. The study population consisted of adult acromegalic patients treated for at least 3 injections of ATG120. The endpoints were: percentage of patients treated with ATG120 at an extended dosing interval (> 4 weeks), mean time between injections, and the cost of ATG120 during a 24-month prospective observation. Costs were calculated in PLN from the public health-care payer and patient perspective for the year 2014. RESULTS: 143 patients were enrolled in, and 132 completed (70% women, 81% macroadenoma, 75% previous surgery) the analysis. During two years, changes in the treatment pattern were reported in 41 patients: 17% of them had increased injection interval and 10% switched to octreotide LAR and then returned to ATG120. Sixty-three patients (48%) received ATG120 at an extended dosing interval. ATG120 was predominantly administered in an out-patient setting (84%) by a health care professional (97%). CONCLUSIONS: The results demonstrated that extended dosing interval of ATG120 is used in a substantial proportion of patients in routine clinical practice in Poland. Such findings support the potential for ATG120 in reducing treatment burden in the real-world clinical environment.

Optimizing somatostatin analog therapy in acromegaly: long-acting formulations.

Somatostatin peptide analogs have revolutionized the medical treatment of patients with acromegaly. More recent deep intramuscular depot preparations have further improved control, with consistent suppression of growth hormone secretion and optimal lowering of insulin-like growth factor-1. Effective control of growth hormone should, with long-term use, reduce morbidity and mortality from acromegaly and has been shown to result in partial involution of the pituitary adenoma in the majority of treated patients. The currently available depot formulations allow for an injection frequency of 14 days (lanreotide LA 30mg) to 28 days (octreotide LAR 20mg) according to the manufacturers' recommendations. In clinical practice, dose titration by evaluating a growth hormone day profile prior to the next injection can extend the interval between injection (to 6 or even 8 weeks in certain individuals). This is especially true for octreotide LAR, which also has increased flexibility regarding dosage with a 10 and 30mg preparation. The annual 'drug cost' is broadly similar between the two formulations though the additional expenditure on nurse time and clinic visits incurred by an increased injection frequency is a significant consideration. Decreased injection frequency improves acceptability for the patient without a loss in treatment efficacy. A subjective return of typical acromegalic symptoms, such as sweating and headache, also seem to be useful in predicting the timing of the next injection. Other formulations and doses of lanreotide are currently being evaluated, but more interestingly, newer analogs with greater efficacy at the type 5 somatostatin receptor subtype, and pan-receptor analogs, are being developed. These peptides, in conjunction with the likely availability of a growth hormone receptor blocking agent (pegvisomant), will further expand the medical therapy options for patients with acromegaly.