A Multinational Pharmacoeconomic Evaluation of Acute Major Depressive Disorder (MDD): a Comparison of Cost-Effectiveness Between Venlafaxine, SSRIs and TCAs

AbstractMethodsWe conducted a multinational pharmacoeconomic evaluation comparing the immediate release form of a new class of serotonin norepinephrine reuptake inhibitor (SNRI), venlafaxine IR to the selective serotonin reuptake inhibitors (SSRIs) and the tricyclic antidepressants (TCAs) in the treatment of acute major depressive disorder (MDD) in 10 countries (Germany, Italy, Netherlands, Poland, Spain, Sweden, Switzerland, United Kingdom, United States, and Venezuela). We designed a decision analytic model assessing the acute phase of MDD treatment within a 6-month time horizon. Six decision tree models were customized with country-specific estimates from a clinical management analysis, meta-analytic rates from two published meta-analyses, and a resource valuation of treatment costs representing the inpatient and outpatient settings within each country. The meta-analyses provided the clinical rates of success defined as a 50% reduction in depression scores on the Hamilton Depression Scale (HAM-D) or the Montgomery-Asberg Depression Rating Scale (MADRS). Treatment regimen costs were determined from standard lists, fee schedules, and communication with local health economists in each country. The meta-analytic rates were applied to the decision analytic model to calculate the expected cost and expected outcomes for each antidepressant comparator. Cost-effectiveness was determined using the expected values for both a successful outcome, and a composite measure of outcome termed symptom-free days. A policy analysis was conducted to examine the health system budget impact in each country of increasing the utilization of the most effective antidepressant found in our study.ResultsInitiating treatment of MDD with venlafaxine IR yielded a lower expected cost compared to the SSRIs and TCAs in all countries except Poland in the inpatient setting, and Italy and Poland within the outpatient settings. The weighted average expected cost per patient varied from US$632 (Poland) to US$5647 (US) in the six-month acute phase treatment of MDD. The estimated total budgetary impact for each 1% of venlafaxine utilization, assuming a population of one million MDD patients, ranged from US$1600 (Italy) to US$29,049 (US).ConclusionsWithin the inpatient and outpatient treatment settings, venlafaxine IR was a more cost-effective treatment of MDD compared to the SSRIs and TCAs. Additionally, the results of this investigation indicate that increased utilization of venlafaxine in most settings across Europe and the Americas will have favorable impact on health care payer budgets.ADR, adverse drug reaction; CMA, clinical management analysis; ECT, electroconvulsive therapy; HAM-D, Hamilton Depression Scale; MADRS, Montgomery-Asberg depression rating scale; MDD, major depressive disorder; SFD, symptom-free day; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; TCA, tricyclic antidepressant; WHO, world health organization

PCN20 MAINTENANCE ERLOTINIB VERSUS PEMETREXED FOR THE TREATMENT OF NON-SMALL CELL LUNG CANCER: INDIRECT COMPARISON APPLYING REAL-LIFE OUTCOMES

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Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison

Background: Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. Methods: Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. Results: Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. Conclusions: The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments

Real-world impact of fremanezumab on migraine symptoms and resource utilization in the United States

BACKGROUND: Fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), is approved for migraine prevention in adults. Real-world data on the effectiveness of fremanezumab are limited. This retrospective, observational cohort study assessed patient-reported migraine symptoms, health care resource utilization (HCRU), and direct medical costs before and after fremanezumab treatment initiation. METHODS: Data were extracted from September 2018 through June 2020 from the Midwest component of EMRClaims+®, an integrated health services database containing \u3e 20 million medical records from national commercial insurance claims, Medicare claims, and regional electronic medical records. Patients included in the cohort analysis were aged ≥ 18 years and were administered fremanezumab, with enrollment or treatment history for ≥ 6 months prior (pre-index) to initiating fremanezumab (index date) and ≥ 1 month after the index date (post-index), and without pregnancy or pregnancy-related encounters during the study period. Patient-reported headache frequency, migraine pain intensity (MPI), composite migraine symptoms, and HCRU were assessed pre-index and ≥ 1 month after fremanezumab initiation. Wilcoxon signed-rank tests were used to compare means of migraine symptoms and outcomes and HCRU before and after fremanezumab initiation. RESULTS: Overall, 172 patients were eligible for analysis. Of patients who self-reported (n = 129), 83.7% reported improvement in headache frequency or symptoms after fremanezumab treatment. Specifically, headache frequency decreased by 63% after fremanezumab initiation: mean (standard deviation) headache frequency was 22.24 (9.29) days per month pre-index versus 8.24 (7.42) days per month post-index (P \u3c 0.0001). Mean MPI also decreased by 18% after fremanezumab initiation: MPI was 5.47 (3.19) pre-index versus 4.51 (3.34) post-index (P = 0.014). Mean emergency room (ER) visits per month decreased from 0.72 to 0.54 (P = 0.003), and mean outpatient visits per month decreased from 1.04 to 0.81 (P \u3c 0.001). Mean hospitalizations per month decreased, but the results did not reach statistical significance (P = 0.095). Hospitalization and ER costs decreased, while outpatient costs increased, from pre-index to post-index, but differences were not statistically significant (P ≥ 0.232). CONCLUSIONS: Significant reductions in headache frequency, MPI, and HCRU were observed after fremanezumab initiation in patients with migraine in a US real-world setting

The Grizzly, September 18, 1987

Union to Be Bumped to Wismer • Tremper Tackles New College Art Facilities • Constitution Celebrates 200th • Monthly Film Series Started • REM: Documental Proof • Letters: Parking a Problem; Light the Lounge! • Bet They Didn\u27t Get U.C. • Ec / BA Invests • Reaching for STARs • Notes: Oct. 11 Will be a Super Sunday; Myrin Hosts Art Exhibit; Annual Fall Book Sale to Begin • Despite Hopes, Bears Lose 21-0 • Men Harriers Ace First Tryst • Runner O\u27Donohue Athlete of the Week for Record Fourth Time • Fourth Down for the NFL • Hockey Ties Place in Season Openers • Forum to Present Peace • Ursinus in Kutztown? • New Look for Myrin • Jazz Kicks off Forum Fine Arts Serieshttps://digitalcommons.ursinus.edu/grizzlynews/1192/thumbnail.jp

MYC regulates fatty acid metabolism through a multigenic program in claudin-low triple negative breast cancer

Background: Recent studies have suggested that fatty acid oxidation (FAO) is a key metabolic pathway for the growth of triple negative breast cancers (TNBCs), particularly those that have high expression of MYC. However, the underlying mechanism by which MYC promotes FAO remains poorly understood. Methods: We used a combination of metabolomics, transcriptomics, bioinformatics, and microscopy to elucidate a potential mechanism by which MYC regulates FAO in TNBC. Results: We propose that MYC induces a multigenic program that involves changes in intracellular calcium signalling and fatty acid metabolism. We determined key roles for fatty acid transporters (CD36), lipases (LPL), and kinases (PDGFRB, CAMKK2, and AMPK) that each contribute to promoting FAO in human mammary epithelial cells that express oncogenic levels of MYC. Bioinformatic analysis further showed that this multigenic program is highly expressed and predicts poor survival in the claudin-low molecular subtype of TNBC, but not other subtypes of TNBCs, suggesting that efforts to target FAO in the clinic may best serve claudin-low TNBC patients. Conclusion: We identified critical pieces of the FAO machinery that have the potential to be targeted for improved treatment of patients with TNBC, especially the claudin-low molecular subtype

Prognostic value of increase in transcript levels of Tp73 ΔEx2-3 isoforms in low-grade glioma patients

Glial tumours are a devastating, poorly understood condition carrying a gloomy prognosis for which clinicians sorely lack reliable predictive parameters facilitating a sound treatment strategy. Tp73, a p53 family member, expresses two main classes of isoforms – transactivatory activity (TA)p73 and ΔTAp73 – exhibiting tumour suppressor gene and oncogene properties, respectively. The authors examined their expression status in high- and low-grade adult gliomas. Isoform-specific real-time reverse transcription-polymerase chain reaction was used for the analysis of Tp73 isoform transcript expression in a series of 51 adult patients harbouring glial tumours, in order to compare tumour grades with each other, and with non-tumoural samples obtained from epileptic patients as well. Our data demonstrate increase of TAp73 and ΔTAp73 transcript levels at onset and early stage of the disease. We also show that ΔEx2–3 isoform expression in low-grade tumours anticipates clinical and imaging progression to higher grades, and correlates to the patients' survival. Expression levels of P1 promoter generated Tp73 isoforms – and particularly ΔEx2–3 – indeed allow for prediction of the clinical progression of low-grade gliomas in adults. Our data are the first such molecular biology report regarding low-grade tumours and as such should be of help for sound decision-making