INES: Interactive tool for construction and extrapolation of partitioned survival models.

BACKGROUND: INES (INteractive model for Extrapolation of Survival and cost) provides an open-access tool powered by R that implements three-state partitioned survival models (PSM). This article describes the properties of the tool, and the situations where INES may or may not be suitable. METHODS: INES is designed to be used by investigators or healthcare professionals who have a good grasp of the principles of economic evaluation and understand the strengths and weaknesses of partitioned survival models, but are not sufficiently familiar with a statistical package such as Excel or R to be able to construct and test a de-novo PSM themselves. INES is delivered to the user via a batch file. Once downloaded to the user's hard drive, it interacts with the user via a portable version of R with web interactivity built in Shiny. INES requires absolutely no knowledge of R and the user does not need to have R or any of its dependences installed. Hence the user will deal with a standalone Shiny app. Inputs (digitalized survival curves, unit costs, posology, hazard ratios, discount rate) can be uploaded from a template spreadsheet. RESULTS: The INES application provides a seamlessly integrated package for estimating a set of parametric hazard functions for progression free and overall survival, selecting an appropriate function from this menu, and applying this as an input to a PSM to calculate mean costs and quality-adjusted life years. Examples are given that may serve as a tutorial. CONCLUSION: INES offers a rapid, flexible, robust and transparent tool for parametric survival analysis and calculating a PSM that can be used in many different contexts.

Olaparib as first line in BRCA-mutated advanced ovarian carcinoma: Is it cost-effective in Spain?

OBJECTIVE: To estimate the cost-effectiveness of olaparib after being funded by the Spanish National Health Service (SNHS) as first-line monotherapy maintenance treatment in patients with advanced high-grade serous ovarian carcinoma (HGSOC) and BRCA mutations in Spain. METHODS: A semi-Markov model with one-month cycles was adapted to the Spanish healthcare setting, using the perspective of the SNHS, and a time horizon of 50 years. Two scenarios were compared: receiving olaparib vs. no maintenance treatment. The model comprised four health states and included the clinical results of the SOLO1 study, along with the direct healthcare costs associated with the use of first-line and subsequent treatment resources (2020 €). A discount rate of 3% was applied for future cost and quality-of-life outcomes. A probabilistic sensitivity analysis (PSA) was also carried out and a cost-effectiveness threshold of €25,000 per quality adjusted life year (QALY) was considered. RESULTS: The introduction of olaparib as a first-line maintenance treatment for advanced HGSOC patients with BRCA mutations implied a cost of €131,614.98 compared to €102,369.54 without olaparib (difference: €29,245.44), with an improvement of 2.00 QALYs (5.56 and 3.57, respectively). Therefore, olaparib is cost-effective for advanced HGSOC patients with BRCA mutations, with an incremental cost-effectiveness ratio of €14,653.2/QALY. The results from the PSA showed that 92.1% of the simulations fell below the €25,000/QALY threshold. The model showed that olaparib could improve the overall survival by 2 years, vs. no maintenance treatment. CONCLUSIONS: Olaparib as first-line maintenance treatment is cost-effective in advanced HGSOC patients with BRCA mutations in Spain.

Analysis of first-line treatment in older patients with metastasic colorectal cancer.

OBJECTIVE: The purpose of this study was to analyse the effectiveness and safety of first-line treatment of metastatic colorectal cancer (CRCm) in older patients treated in a tertiary hospital. MATERIAL AND METHODS: This was an observational and retrospective study, including patients aged 75 years or older, with CRCm, who received chemotherapy treatment in 2017. The main variables studied were type of treatment, Progression-Free Survival (PFS), Overall Survival (OS), dose reductions, and treatment delays due to adverse events. RESULTS: A total of 59 patients (71.2% men) with a median age of 76 years were enrolled in this study. About 70% presented colon cancer, with the left colon being the most frequent location. They were treated with 9 different schemes, in most cases using polychemotherapy and biological agents. The median PFS and OS was 12 and 30 months, respectively. A total of 23/59 of patients started treatment at doses lower than recommended in the clinical practice guidelines. In terms of safety, 34/59 of patients had at least one dose reduction, and 30/59 suffered one treatment delay. The most frequent adverse reactions were asthenia, peripheral neuropathy, diarrhoea, and palmoplantar erythrodysesthesia. CONCLUSION: Our patients presented baseline clinical characteristics similar to the general adult population, with no tumour characteristics associated with advanced age. The efficacy and toxicity were similar to those in the clinical trials, although our patients had more dose reductions. Considering the heterogeneity of patients and in the absence of clinical trials in the older population, real-life studies can be very useful.

Network meta-analysis of first-line treatments in transplant-ineligible multiple myeloma patients.

OBJECTIVES: Multiple myeloma (MM) is a complex disease. Lack of direct comparisons among treatments and incorporation of new alternatives make it necessary to perform studies that allow for clinical decision-making. A network meta-analysis (NMA) was developed to evaluate the comparative efficacy among different therapeutic alternatives in newly diagnosed transplant-ineligible MM patients. METHODS: MEDLINE® and EMBASE® were systematically searched up for these drugs: lenalidomide, thalidomide, bortezomib, and daratumumab. Comparative phase II-III randomized clinical trials (RCTs) were included. Progression-free survival (PFS) was selected as efficacy outcome. The NMA was developed using Bayesian methods. Fixed- and random-effects models were assessed using deviance information criteria. RESULTS: The systematic search yielded 593 results. Ten RCTs were included. No differences were observed between fixed- and random-effects models. The combination of daratumumab, bortezomib, melphalan, and prednisone showed the best HR in PFS (reference treatment). Along with this scheme, the best PFS results were obtained by combination of daratumumab, lenalidomide, and dexamethasone (HR 1.2, 95% CrI 0.64-2.4) and bortezomib with lenalidomide and dexamethasone (HR 1.6, 95% CrI 0.81-3.0). CONCLUSIONS: Schemes with the best PFS results were daratumumab treatments and combination of bortezomib, lenalidomide, and dexamethasone, although the latter scheme has been analyzed in heterogeneous populations.

Network meta-analysis of tofacitinib versus biologic treatments in moderate-to-severe rheumatoid arthritis patients.

WHAT IS KNOWN AND OBJECTIVE: Rheumatoid arthritis (RA) is an autoimmune disease characterized primarily by inflammation and pain in the joints. Tofacitinib is an oral drug recently approved for RA treatment; it inhibits Janus protein kinases (JAK) that reduces RA symptoms when conventional DMARDs do not trigger a response. This study aimed to compare the efficacy of biological DMARDs in monotherapy or combined with methotrexate in RA patients and compare the treatments. METHODS: We reviewed the literature for articles published up to June 2017, evaluating the efficacy and safety of the biological DMARDs indicated for RA in patients with inadequate responses to conventional DMARDs and naïve to biological DMARDs, in similar populations, considering ACR50 as the efficacy variable. The odds ratio (OR) and 95% confidence interval (CI) were calculated for each drug combination, and these parameters were transformed into differences in responses to assess the effectiveness of the alternative medicines. Equivalence therapeutic alternatives (ETA) were ensured to assess the possibility of considering these medications with equivalent efficacy. A network meta-analysis (NMA) was performed using Bayesian approaches and the fixed-effects model. RESULTS AND DISCUSSION: Twenty-seven randomized clinical trials (RCTs) that met the pre-established criteria were identified. The 95% CI of biological DMARDs was higher than that of placebo without methotrexate, except for certolizumab, golimumab-m, anakinra-m and adalimumab monotherapy. These DMARDs performed significantly better than the placebo, except for etanercept, certolizumab, tofacitinib and golimumab. Certolizumab-m was better than anakinra-m and adalimumab, and tocilizumab alone or combined with methotrexate was superior to adalimumab. Etanercept-m yielded a higher difference in responses compared with the other biological DMARDs, which presented more homogeneous responses, except for adalimumab and anakinra-m, which yielded worse results. None of the biological DMARDs displayed ETA to etanercept-m; however, they displayed ETA with certolizumab-m, except for adalimumab and anakinra-m. WHAT IS NEW AND CONCLUSION: All biological DMARDs used in combination with methotrexate, except for etanercept, anakinra, certolizumab and tocilizumab without methotrexate, were displayed ETA on using ACR50 at week 24 in patients naïve to biological DMARDs. Etanercept displayed a greater difference in responses, although the high uncertainty of the comparative results prevented the confirmation of the increased efficacy of this drug.

Cost-effectiveness analysis of sofosbuvir-based regimens for chronic hepatitis C.

BACKGROUND: A new scenario of therapy for chronic hepatitis C (CHC) is being established with the approval of sofosbuvir (SOF). OBJECTIVE: To estimate the cost-effectiveness of SOF-based regimens approved in the Summary of Product Characteristics (SmPC) versus the standard of care for different genotypes and patient populations (naive or pretreated). METHODS: A Markov model simulating CHC progression was used to estimate disease treatment costs and effects over patients' lifetimes, from the Spanish National Public Healthcare System perspective. Different therapeutic options were analysed for genotypes 1, 2 and 3 in naive population and for genotype 2 and 3 pretreated patients, according to data obtained from clinical trials. A one-way sensitivity analysis was performed to evaluate the uncertainty of certain parameters: treatment starting age, transition probabilities, drug costs and discount rate. A probabilistic sensitivity analysis was also carried out. RESULTS: For the naive population, the option SOF+pegylated-interferon-α (pIFN)+ribavirin (RBV) for 12 weeks recorded in SmPC for genotype 1 and 3 versus pIFN+RBV for 24 weeks estimated an incremental cost-effectiveness ratio (ICER) below the €40,000/quality-adjusted life-year (QALY) benchmark. For the pretreated population, SOF triple therapy reached an ICER on the threshold limit for genotype 3. Other options included in SmPC for different genotypes exceeded the accepted efficiency limit in our setting. CONCLUSIONS: The options that included SOF+RBV+pIFN in a 12-week course regimen fell below the efficiency threshold considered in our setting. IFN-free regimens administered for 24 weeks reached figures over the benchmark of €40,000/QALY.

The role of artificial intelligence in scientific publishing: Perspectives from Hospital Pharmacy. / El rol de la inteligencia artificial en la publicación científica: perspectivas desde la farmacia hospitalaria.

The article examines the impact of artificial intelligence on scientific writing, with a particular focus on its application in hospital pharmacy. It analyzes artificial intelligence tools that enhance information retrieval, literature analysis, writing quality, and manuscript drafting. Chatbots like Consensus, along with platforms such as Scite and SciSpace, enable precise searches in scientific databases, providing evidence-based responses and references. SciSpace facilitates the generation of comparative tables and the formulation of queries regarding studies, while ResearchRabbit maps the scientific literature to identify trends. Tools like DeepL and ProWritingAid improve writing quality by correcting grammatical, stylistic, and plagiarism errors. A.R.I.A. enhances reference management, and Jenny AI assists in overcoming writer's block. Python libraries such as LangChain enable advanced semantic searches and the creation of agents. Despite their benefits, artificial intelligence raises ethical concerns including biases, misinformation, and plagiarism. The importance of responsible use and critical review by experts is emphasized. In hospital pharmacy, artificial intelligence can enhance efficiency and precision in research and scientific communication. Pharmacists can use these tools to stay updated, enhance the quality of their publications, optimize information management, and facilitate clinical decision-making. In conclusion, artificial intelligence is a powerful tool for hospital pharmacy, provided it is used responsibly and ethically.

Dacomitinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: To assess the cost-effectiveness of first-line treatment with dacomitinib compared with gefitinib in patients newly diagnosed with advanced NSCLC EGFR-positive in the context of Spain. Materials & methods: A partitioned survival model was developed including costs, utilities and disutilities to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with dacomitinib versus gefitinib. Results: Dacomitinib presented higher QALYs (0.51) compared with gefitinib (0.45). Dacomitinib costs were €33,061 in comparison with €26,692 for gefitinib arm. An incremental cost-effectiveness ratio of €111,048 was obtained for dacomitinib. Conclusion: Dacomitinib was more effective in terms of QALYs gained than gefitinib. However, to obtain a cost-effectiveness alternative, a discount greater than 25% in dacomitinib acquisition cost is required.

Cost-effectiveness analysis of infliximab, adalimumab, golimumab, vedolizumab and tofacitinib for moderate to severe ulcerative colitis in Spain.

OBJECTIVE: Despite the biological drugs, the treatment of moderate to severe ulcerative colitis is still a challenge, particularly in resource-limited settings. The aim of this study was to assess the efficiency of biological drugs and tofacitinib for moderate to severe ulcerative colitis in the Spanish context. METHODS: A Markov model was built to simulate the progression of moderate to severe ulcerative colitis in a cohort of patients. The model used a time horizon of 10 years. The perspective chosen was the National Health Service, with a discount rate of 3%, and a threshold of €30,000/quality adjusted life-year (QALY). It carried out a one-way sensitivity analysis and probabilistic sensitivity analysis. RESULTS: The comparison of infliximab with adalimumab and golimumab estimated an incremental cost-effectiveness ratio (ICER) of €43,928.07/QALY and €31,340.69/QALY, with a difference of - 0.43 and - 0.82 QALY, respectively. Vedolizumab vs infliximab achieved an ICER of €122,890.19/QALY with a gain of 0.46 QALY. The comparison of infliximab with tofacitinib yielded an estimated ICER of €270,503.19/QALY, with a slight gain in QALY (0.16). The one-way sensitivity analysis showed a robust study. CONCLUSION: For a threshold of €30,000/QALY, adalimumab was the most cost-effective treatment versus infliximab for moderate to severe ulcerative colitis in Spain.

Cost-effectiveness analysis of second-line pharmacological treatment of acromegaly in Spain.

Objective: To estimate the cost-effectiveness of second-line pharmacological treatments in patients with acromegaly resistant to first-generation somatostatin analogues (FG SSA) from the Spanish National Health System (NHS) perspective.Methods: A Markov model was developed to analyze the cost-effectiveness of pegvisomant and pasireotide in FG SSA-resistant acromegaly, simulating a cohort of patients from the treatment beginning to death. Treatment with pegvisomant or pasireotide was compared to FG SSA retreatment. Efficacy data were obtained from clinical trials and utilities from the literature. Direct health costs were obtained from Spanish sources (€2018).Results: The Incremental Cost Effectiveness Ratio (ICER) of pegvisomant vs. FG SSA was €85,869/Quality-adjusted life years (QALY). The ICER of pasireotide vs. FG SSA was €551,405/QALY. The ICER was mainly driven by the incremental efficacy (4.41 QALY for pegvisomant vs. FG SSA and 0.71 QALY for pasireotide vs. FG SSA), with a slightly lower increase in costs with pegvisomant (€378,597 vs. FG SSA) than with pasireotide (€393,151 vs. FG SSA).Conclusion: The ICER of pasireotide compared to FG SSA was six times higher than the ICER of pegvisomant vs. FG SSA. Pegvisomant is a more cost-effective alternative for the treatment of acromegaly in FG SSA-resistant patients in the Spanish NHS.

Osimertinib in first-line treatment of advanced EGFR-mutated non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: Osimertinib improves progression-free survival in first-line EGFR mutation-positive non-small-cell lung cancer. Materials & methods: A Markov cohort model including costs, utilities and disutilities, was conducted to estimate quality-adjusted life-year (QALY) and incremental cost-effectiveness ratio when treating with osimertinib versus standard first-line tyrosine kinase inhibitors (TKIs). Results: Osimertinib presented higher QALYs (0.61) compared with standard EGFR-TKIs (0.42). Osimertinib costs were €83,258.99, in comparison with €29,209.45 for the standard EGFR-TKIs. An incremental cost-effectiveness ratio of €273,895.36/QALY was obtained for osimertinib. Conclusion: Osimertinib was more effective in terms of QALYs gained than comparators (erlotinib-gefitinib). However, to obtain a cost-effectiveness alternative, a discount greater than 60% in osimertinib acquisition cost is required.

Cost-effectiveness of lenalidomide maintenance in patients with multiple myeloma who have undergone autologous transplant of hematopoietic progenitor cells.

The objective of this article is to analyze the ratio of cost-effectiveness and budgetary impact of lenalidomide treatment in patients with multiple myeloma who have undergone autologous transplant in Spain. The analyses were based on clinical trials CALGB 100104 and IFM 2005-02, from the perspective of the National Health System. The alternatives compared were the treatment with lenalidomide against maintenance without treatment (MwT). Efficiency measures used were years of life gained (YGs) and quality-adjusted life years (QALYs). According to the CALGB 100104 trial data, the average health costs of patients who were treated with lenalidomide for 120 months was €836,534.31 and without treatment was €528,963.63. The effectiveness of the lenalidomide group was 7.59YGs (5.72 QALY) against 6.58 of MwT (4.61 QALY). The incremental cost-utility ratio (ICUR) was €277,456.72/QALY and the incremental cost-effectiveness ratio was €303,191.05/YGs. From the analysis, the IFM2005-02 trial obtained 5.13 QALY in the lenalidomide group against the 4.98 QALY in the MwT group, with an ICUR of €1,502,780.55/QALY. In terms of budgetary impact, a range between 799 and 1452 patients susceptible to receive treatment with lenalidomide was assumed in Spain. In conclusion, the results show a high ICUR and budgetary impact, which adds uncertainty about the maximum prudent duration of the treatment.

Systematic review and network meta-analysis of treatment for moderate-to-severe ulcerative colitis.

Background Biological drugs for moderate-to-severe ulcerative colitis have changed the therapeutic perspective, while small-molecule inhibitors and new promising drugs suggest new options. Aim Assess comparative efficacy and safety of biological and new small oral drugs: commercialized and under-investigation ones for patients naïve to biological drugs. Methods A systematic review was conducted to identify the randomized clinical trials phase 2 or 3, in adults with moderate-to-severe ulcerative colitis treated with biological drugs (infliximab, adalimumab, golimumab, vedolizumab and etrolizumab) or new oral small molecules (tofacitinib and ozanimod) as first line. A Bayesian network metaanalysis was performed to inform comparative efficacy and safety of different treatments. Efficacy outcomes were clinical remission, clinical response and mucosal healing for induction therapy and clinical remission, mucosal healing and sustained clinical remission for maintenance therapy. Safety was assessed with serious adverse events and rates of infections. Results 14 references were included for network meta-analysis. For induction therapy, infliximab was the best drug for induction of clinical response and remission, while ozanimod showed to be the best for induction of mucosal healing. Tofacitinib had the highest rate of maintaining clinical remission. All treatments were similar for serious adverse events, and vedolizumab and tofacitinib had the highest rates of infections. Conclusion This network meta-analysis suggests infliximab may be the best therapeutic option for moderate-to-severe ulcerative colitis. Vedolizumab seems to have better outcomes in maintenance than in induction therapy and it appears superior to golimumab and adalimumab. Tofacitinib, ozanimod and etrolizumab show encouraging results.

Cost-effectiveness analysis of infliximab, adalimumab, golimumab and vedolizumab for moderate to severe ulcerative colitis in Spain.

OBJECTIVES: Assess the efficiency of biologic treatment for moderate to severe ulcerative colitis (UC) which are indicated and financed for this pathology by Spain. METHODS: A Markov model was constructed to simulate the progression in a cohort of patients with moderate to severe UC. The perspective chosen was National Health Service with an over 10 years of time horizon, with a discount rate of 3%, and established threshold of €30,000/quality-adjusted life-year (QALY). RESULTS: The comparison between infliximab versus adalimumab achieved an incremental cost-effectiveness ratio (ICER) of €45,582/QALY, with a 0.900 QALYs difference of efficacy and an incremental cost of €41,036. Golimumab versus adalimumab reached an ICER of €2,175,992/QALY, with a difference of 0.001 QALY in efficacy and a raising cost to €2,611. The comparison between vedolizumab with adalimumab achieved an ICER of €90,532/QALY, 0.930 QALYs of difference and an increasing cost of €84,218. The probabilistic sensitivity analysis shows that adalimumab would be cost-effective in the 65.2% of the simulations, infliximab in the 18.4%, golimumab in the 16.4% and vedulizumab for the 0%. CONCLUSIONS: Among all these drugs studied, adalimumab is the most cost-effective drug for the treatment of moderate to severe UC for a threshold of €30,000/QALY in Spain.

Cost-effectiveness and Budget Impact of Treatment with Evolocumab Versus Statins and Ezetimibe for Hypercholesterolemia in Spain.

INTRODUCTION AND OBJECTIVES: To analyze the cost-effectiveness ratio and budget impact of treatment with evolocumab (PCSK9 inhibitor) for patients in secondary prevention in the Spanish National Health System. METHODS: A budget impact analysis, decision tree and Markov models were designed under the public health system perspective, based on the only study with morbidity and mortality data (FOURIER). The alternatives compared were evolocumab vs statins, and dual therapy with ezetimibe in 5% of the population. The measure of effectiveness used was the number of cardiovascular events avoided. Univariate and probabilistic sensitivity analyses were performed. RESULTS: The average annual cost of patients receiving evolocumab was 11 134.78€ and 393.83€ for standard treatment (statins plus ezetimibe). The incremental cost-effectiveness ratio was > 600 000 € per avoided cardiovascular event for both assessed outcomes (first: cardiovascular death, myocardial infarction, stroke, and hospitalization due to unstable angina or coronary revascularization; second: includes the first 3 events). To perform the 10-year Markov model, the average cost of standard treatment was 13 948.45€ vs 471 417.37€ with evolocumab. Treatment with evolocumab for patients with familial hypercholesterolemia would cost between 3 and 6.1 million euros, assuming a difference of 2.5 and 5.1 million euros with the standard treatment (2017). This difference would be between 204.3 and 1364.7 million euros (2021) for those with nonfamiliar hypercholesterolemia (secondary prevention). CONCLUSIONS: Treatment with evolocumab is associated with a lower frequency of cardiovascular events, but is inefficient for patients suitable to receive this drug in the Spanish National Health System.

Cost-effectiveness analysis of therapeutic options for chronic hepatitis C genotype 3 infected patients.

BACKGROUND: This study provides a cost-effectiveness analysis of therapeutic strategies for chronic hepatitis C genotype 3 infected patients in Spain. METHODS: A Markov model was designed to simulate the progression in a cohort of patients aged 50 years over a lifetime horizon. RESULTS: Sofosbuvir (SOF) plus peginterferon and ribavirin for 12 weeks was a cost-effective option when compared to standard of care (SoC) in the treatment of both 'moderate fibrosis' and 'cirrhotic' patients. Incremental cost-effectiveness ratios were €35,276/QALY and €18,374/QALY respectively. ICERs for SOF plus daclatasvir (DCV) regimens versus SoC were over the threshold limit considered, at €56,178/QALY and €77,378/QALY for 'moderate fibrosis' and 'cirrhotic' patients respectively. CONCLUSION: Addition of SOF to IFN-based regimens for genotype 3 was cost-effective for both 'moderate fibrosis' and 'cirrhotic' patients. IFN-free options including SOF and DCV association required price reductions lower than the list prices to be considered cost-effective.

Cost-effectiveness analysis of simeprevir with daclatasvir for non-cirrhotic genotype-1b-naïve patients plus chronic hepatitis C.

BACKGROUND: The cost of interferon-free combination therapies remains high to provide widespread access to treatment, regardless of fibrosis stage. AIM: To estimate the cost-effectiveness of simeprevir/daclatasvir (SMV/DCV) therapy in treatment-naïve chronic hepatitis C genotype-1b patients with moderate fibrosis. METHODS: A Markov model was developed to simulate the natural history of chronic hepatitis C progression. The model estimated lifetime healthcare costs and quality-adjusted life-years (QALY) for a cohort of patients from the Spanish National Healthcare System perspective. The cost-effectiveness threshold considered was €40,000/QALY. The treatment strategies analyzed were SMV/DCV, peginterferon/ribavirin/telaprevir, and peginterferon/ribavirin/boceprevir. A sensitivity analysis was carried out. RESULTS: The incremental cost-effectiveness ratios of the SMV/DCV strategy were €23,774/QALY and €28,524/QALY compared with that of telaprevir or boceprevir triple therapy, respectively, for genotype-1b patients with moderate fibrosis. CONCLUSIONS: SMV/DCV combination compared with the standard of care previous to the arrival of second-generation direct-acting antivirals fell below generally accepted willingness-to-pay threshold. Results obtained should be supported by ongoing clinical trials.

[Cost-effectiveness analysis of sofosbuvir-simeprevir regimens for chronic hepatitis C genotype 1 patients with advanced fibrosis]. / Análisis coste-efectividad del tratamiento de la hepatitis C crónica con sofosbuvir-simeprevir en pacientes con genotipo 1 y fibrosis avanzada.

BACKGROUND AND OBJECTIVE: The aim of this study was to measure the cost-effectiveness of the treatment with simeprevir and sofosbuvir in chronic hepatitis C genotype 1 patients with F3-F4 levels of fibrosis, according to the results of the COSMOS trial. MATERIAL AND METHODS: A Markov model was used to estimate the costs and clinical outcomes from the start of therapy. In the model, the progression was simulated alongside the different health states of the chronic liver disease associated with chronic hepatitis C using whole life as time-horizon. RESULTS: The 12-weeks treatment schemes was below the threshold of €40,000 per quality-adjusted life year. On the contrary, despite the 50% cost reduction, the 24-weeks regimen demonstrated a limited level of efficiency when compared with the willingness to pay used in the Spanish medical literature. CONCLUSIONS: This finding would support the introduction of a flat rate in the price of drugs without taking into account the duration of treatment to ensure that treatment with 24 weeks was efficient.

Sofosbuvir plus simeprevir for the treatment of genotype 1 chronic hepatitis C: a review of evidence.

INTRODUCTION: Sofosbuvir (SOF) with simeprevir (SIM) combination was the first interferon-free regimen that reached optimal results in terms of sustained viral response (SVR). Areas covered: A systematic review of the scientific literature concerning the effects that the SOF/SIM combination had on hepatitis C genotype 1 patients yielded 771 references. After the revision process, four clinical trials and 15 observational studies met the inclusion criteria; in total, these studies involved 5,766 patients. The SVR ranged from 67% to 100% depending on the patients' viral subtype and cirrhosis status. Adverse effects were common, but treatment discontinuation related to drug toxicity occurred in less than 5% of cases. Expert commentary: The SOF/SIM combination exhibits efficacy and tolerability profiles that are similar to those of the other available interferon-free combinations used for non-cirrhotic genotype 1b patients. Meanwhile, for patients with advanced cirrhosis or genotype 1a, this approach cannot be considered a routine treatment option due to the unsatisfactory results.

Trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel in the neoadjuvant setting of HER-2 positive breast cancer.

BACKGROUD: Neoadjuvant treatment based on the combination of trastuzumab plus chemotherapy is the standard of care in patients with HER2-positive early or locally advanced breast cancer. The concurrent use of trastuzumab, anthracyclines and taxanes is frequently used in this setting despite the potential cardiotoxicity of both anthracyclines and trastuzumab. However, not much information is available about this chemotherapy scheme. OBJECTIVE: We wanted to evaluate the efficacy and safety profile of the combination of trastuzumab, liposome-encapsulated doxorubicin and paclitaxel as neoadjuvant scheme. We also tried to establish predictive factors of pathologic complete response. SETTING: The study was carried out in a tertiary University Hospital of Spain. METHOD: This is a descriptive study of the clinical practice performed in our hospital. MAIN OUTCOME MEASURE: Efficacy was measured in terms of pathologic complete response, which was defined as the absence of invasive cancer cells in the breast and the axilla after neoadjuvant treatment. RESULTS: Thirty patients were included, the median age was 48. Seventeen (56.7 %) were hormonal receptor (HR) positive, 14 (46.6 %) had IIIa-b clinical stage and one of them had inflammatory breast cancer. 12 patients (40 %) achieved pCR. Patients with HR-negative BC achieved a higher pCR rate than those ones with HR-positive BC (61.5 % and 23.5 %, respectively; p value = 0.035). 21 patients (70 %) underwent breast conservative surgery. The treatment was in general well tolerated, most frequent grade 3-4 adverse events were neutropenia (20 %), asthenia and liver enzyme alteration (10 %) and febrile neutropenia (6.7 %). No patient developed heart failure, but one (3.3 %) presented a 10 % asymptomatic absolute reduction in left ventricular fraction ejection. CONCLUSIONS: The studied treatment for the neoadjuvant setting of HER2 positive breast cancer seems to be an effective therapeutic option. Despite the expected high rate of cardiotoxicity of this regimen, the study results shows that this treatment regimen appears to be safe. The combination of trastuzumab, non-pegylated liposomal-encapsulated doxorubicin and paclitaxel should be considered for the treatment of HER2-overexpressing breast cancer.