Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis.

Background: Atopic dermatitis is a chronic relapsing inflammatory skin condition. One of the most common skin disorders in children, atopic dermatitis typically manifests before the age of 5 years, but it can develop at any age. Atopic dermatitis is characterised by dry, inflamed skin accompanied by intense itchiness (pruritus). Objectives: To appraise the clinical and cost effectiveness of abrocitinib, tralokinumab and upadacitinib within their marketing authorisations as alternative therapies for treating moderate-to-severe atopic dermatitis compared to systemic immunosuppressants (first-line ciclosporin A or second-line dupilumab and baricitinib). Data sources: Studies were identified from an existing systematic review (search date 2019) and update searches of electronic databases (MEDLINE, EMBASE, CENTRAL) to November 2021, from bibliographies of retrieved studies, clinical trial registers and evidence provided by the sponsoring companies of the treatments under review. Methods: A systematic review of the clinical effectiveness literature was carried out and a network meta-analysis undertaken for adults and adolescents at different steps of the treatment pathway. The primary outcome of interest was a combined response of Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4; where this was consistently unavailable for a step in the pathway, an analysis of Eczema Area and Severity Index 75 was conducted. A de novo economic model was developed to assess cost effectiveness from the perspective of the National Health Service in England. The model structure was informed through systematic review of the economic literature and by consulting clinical experts. Effectiveness data were obtained from the network meta-analysis. Costs and utilities were obtained from the evidence provided by sponsoring companies and standard UK sources. Results: Network meta-analyses indicate that abrocitinib 200 mg and upadacitinib 30 mg may be more effective, and tralokinumab may be less effective than dupilumab and baricitinib as second-line systemic therapies. Abrocitinib 100 mg and upadacitinib 15 mg have a more similar effectiveness to dupilumab. Upadacitinib 30 and 15 mg are likely to be more effective than ciclosporin A as a first-line therapy. Upadacitinib 15 mg, abrocitinib 200 and 100 mg may be more effective than dupilumab in adolescents. The cost effectiveness of abrocitinib and upadacitinib for both doses is dependent on the subgroup of interest. Tralokinumab can be considered cost-effective as a second-line systemic therapy owing to greater cost savings per quality-adjusted life-year lost. Conclusions: The primary strength of the analysis of the three new drugs compared with current practice for each of the subpopulations is the consistent approach to the assessment of clinical and cost effectiveness. However, the conclusions are limited by the high uncertainty around the clinical effectiveness and lack of data for the primary outcome for comparisons with baricitinib and for the adolescent and adult first-line populations. Future work and limitations: The most significant limitation that Eczema Area and Severity Index 50 + Dermatology Life Quality Index ≥ 4 could not be obtained for the adolescent and adult first-line systemic treatment populations is due to a paucity of data for dupilumab and ciclosporin A. A comparison of the new drugs against one another in addition to current practice would be beneficial to provide a robust view on which treatments are the most cost-effective. Study registration: This study is registered as PROSPERO CRD42021266219. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: 135138) and is published in full in Health Technology Assessment; Vol. 28, No. 4. See the NIHR Funding and Awards website for further award information.

Atopic dermatitis is one of the most common skin conditions in children but can also develop in adulthood. People with atopic dermatitis have dry, red (inflamed) skin that is also extremely itchy (pruritus). There is no cure for atopic dermatitis. Therapy starts with topical treatments that are applied to the skin, such as emollients. Severe forms of atopic dermatitis are often treated with systemic treatments, which are drugs that are provided as tablets or an injection. Ciclosporin A is often the first systemic therapy given. If atopic dermatitis does not get better with ciclosporin A, options available in the National Health Service are dupilumab and baricitinib. New therapies that have been evaluated in clinical trials for atopic dermatitis but have not been assessed for use in the National Health Service are abrocitinib, tralokinumab and upadacitinib. The aim of this project is to review the medical benefits, risks and value for money for the National Health Service of abrocitinib, tralokinumab and upadacitinib for the treatment of moderate-to-severe atopic dermatitis in a multiple technology appraisal. Our review found that: For children aged between 12 and 18 years, abrocitinib and a low dose of upadacitinib (15 mg) are good value for money for the National Health Service. For adults who need a first systemic treatment, upadacitinib is unlikely to be good value for money for the National Health Service. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, upadacitinib 15 mg and tralokinumab could be good value for money for the National Health Service if they are used on their own. For adults who are still suffering from their atopic dermatitis after having a systemic treatment and need a different drug, but need to take it with steroid cream, abrocitinib 100 mg, upadacitinib 15 mg and tralokinumab could all be good value for money for the National Health Service.

Biologic Therapy for Ulcerative Colitis.

Five biologics are approved for the treatment of ulcerative colitis (UC): infliximab, adalimumab, golimumab, vedolizumab, and ustekinumab. These drugs have varying levels of efficacy and are recommended as first-line treatment of moderate to severe UC. There has been only 1 head-to-head trial comparing the efficacy of the biologics, adalimumab and vedolizumab, which has important implications for management. Therapeutic drug monitoring of biologics, especially anti-TNF alpha agents, may improve the long-term efficacy of these agents. The future of treatment may include personalization of medications, based on patient-specific and disease-specific characteristics as well as biomarkers, along with appropriate therapeutic drug monitoring.

A Critical Look at the Efficacy and Costs of Biologic Therapy for Chronic Rhinosinusitis with Nasal Polyposis.

PURPOSE OF REVIEW: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent disease that results in significant healthcare-related costs as well as costs to society with lost productivity and time. Unfortunately, a significant percentage of patients who suffer with this disease will not find relief from current standard of care medications and surgery. With ongoing efforts to understand the pathophysiology of CRSwNP has come the introduction of monoclonal antibodies, or "biologics," targeting specific elements of the inflammatory pathway in CRSwNP. Despite efficacy, these come at significant cost and, to date, no studies on the cost-efficacy of these biologics in CRSwNP have been published. RECENT FINDINGS: Multiple studies have now demonstrated efficacy for biologics in the treatment of CRSwNP as a primary indication. However, the gains in quality of life and objective measures, while consistent, are small and, arguably, the clinical significance is still unclear. In addition, the high cost of these medications may be hard to justify when evaluated in cost-efficacy studies against standard of care therapy in CRSwNP. Furthermore, while the current literature is most robust in showing the benefit of the biologics in asthma, it does not fully support cost-efficacy for biologics. This review evaluates the current literature regarding efficacy of monoclonal antibodies for the treatment of CRSwNP and considers this efficacy in light of the cost implications to individuals and society.

The Headache Pipeline: Excitement and Uncertainty.

There are many new treatment options available for migraine and more are coming. Three calcitonin gene-related peptide (CGRP) antagonist monoclonal antibodies have been approved and a 4th is due in early 2020. Small molecule CGRP receptor-blocking oral compounds, both for acute care and prevention, are also coming. Four neurostimulators are available, with others on the way. New acute treatments coming soon include the 5HT1F agonist lasmiditan, a zolmitriptan intradermal micro-needle patch, and a nasal mist sumatriptan with a permeability enhancer. Farther out, three novel dihydroergotamine delivery systems, and a liquid-filled capsule of celecoxib show early promise. A new, safer form of methysergide is in the works, as is a longer-duration onabotulinumtoxinA. As always with new products, questions regarding safety, tolerability, cost, and insurance coverage will need to be addressed. Despite these concerns and uncertainties, a robust headache treatment pipeline is good for patients who are not satisfied with the results of their treatment and/or cannot tolerate existing treatments.

[Developability assessment with case studies highlighting the decision taking]. / Exemples d'études de développabilité apportant un éclairage à la prise de décision.

Therapeutic antibodies generation has to be faster with less development costs. This requires combination of in silico predictions associated with cutting edge screening and characterization technologies. Here, non-exhaustive examples illustrate this simultaneity need.

TITLE: Exemples d'études de développabilité apportant un éclairage à la prise de décision. ABSTRACT: De nos jours, la génération d'anticorps thérapeutiques doit être plus rapide avec des coûts de développement moins importants. Pour cela, des prédictions in silico sont associées à des technologies de criblage et de caractérisation de pointe. Les exemples choisis ici sont non-exhaustifs mais illustrent ce besoin de travailler en parallèle.

Persistence rates and medical costs of biological therapies for psoriasis treatment in Japan: a real-world data study using a claims database.

BACKGROUND: Biological therapies (BTs) including infliximab (IFX), adalimumab (ADL), secukinumab (SCK) and ustekinumab (UST) are approved in Japan for the treatment of psoriasis. Although the persistence rates and medical costs of BTs treatment have been investigated in multiple foreign studies in recent years, few such studies have been conducted in Japan and the differences between patients who adhered to treatment and those who did not have not been reported. This study is aimed at investigating the persistence rates and medical costs of BTs in the treatment of psoriasis in Japan, using the real-world data from a large-scale claims database. METHODS: Claims data from the JMDC database (August 2009 to December 2016) were used for this analysis. Patient data were extracted using the ICD10 code for psoriasis and claims records of BT injections. Twelve-month and 24-month persistence rates of BTs were estimated by Kaplan-Meier methodology, and 12-month-medical costs before and after BT initiation were compared between persistent and non-persistent patient groups at 12 months. RESULTS: A total of 205 psoriasis patients treated with BTs (BT-naïve patients: 177) were identified. The 12-month/24-month persistence rates for ADL, IFX, SCK, and UST in BT-naïve patients were 46.8% ± 16.6%/46.8 ± 16.6%, 53.0% ± 14.9%/41.0% ± 15.5%, 55.4%/55.4% (95% CI not available) and 79.4% ± 9.9%/71.9% ± 12.2%, respectively. Statistically significant differences in persistence were found among different BT treatments, and UST was found to have the highest persistence rate. The total medical costs during the 12 months after BT initiation in BT-naïve patients were (in 1000 Japanese Yen): 2218 for ADL, 3409 for IFX, 465 for SCK, 2824 for UST (average: 2828). Compared with the 12-month persistent patient group, the total medical costs in the persistent group was higher (Δ:+ 118), but for some medications such as IFX or UST cost increases were lower for persistent patients. CONCLUSIONS: UST was found to have the highest persistence rate among all BTs for psoriasis treatment in Japan. The 12-month medical costs after BT initiation in the persistent patient group may not have increased as much as in the non-persistent patient group for some medications.

Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

Ixekizumab for Treating Moderate-to-Severe Plaque Psoriasis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

The National Institute for Health and Care Excellence invited Eli Lilly and Company Ltd, the company manufacturing ixekizumab (tradename Taltz®), to submit evidence for the clinical and cost effectiveness of ixekizumab. Ixekizumab was compared with tumour necrosis factor-α inhibitors (etanercept, infliximab, adalimumab), ustekinumab, secukinumab, best supportive care and, if non-biological treatment or phototherapy is suitable, also compared with systemic non-biological therapies and phototherapy with ultraviolet B radiation for adults with moderate-to-severe plaque psoriasis. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Center, was commissioned as the independent Evidence Review Group. This article presents a summary of the company submission, the Evidence Review Group report and the development of the National Institute for Health and Care Excellence guidance for the use of this drug in England and Wales by the Appraisal Committee. The Evidence Review Group produced a critical review of the clinical and cost effectiveness of ixekizumab based on the company submission. The company submission presented three randomised controlled trials identified in a systematic review. All randomised controlled trials were phase III, multicentre placebo-controlled trials including 3866 participants with moderate-to-severe psoriasis. Two trials also included an active comparator (etanercept). All randomised controlled trials showed statistically significant increases in two primary outcomes, static Physician Global Assessment (0,1) and improvement of 75% from baseline in the Psoriasis Area and Severity Index. Ixekizumab was generally well tolerated in the randomised controlled trials, with similar discontinuation rates because of adverse events as placebo or etanercept. The most frequent adverse events of special interest were infections and injection-site reactions. The company submission also included a network meta-analysis of relevant comparators. The Evidence Review Group highlighted some issues regarding the systematic review process and an issue with the generalisability of the findings in that the trials failed to include patients with moderate psoriasis according to a widely used definition. This issue was considered by the Appraisal Committee and the population was deemed generalisable to patients in England and Wales. Based on the network meta-analysis, the Appraisal Committee concluded that ixekizumab was more clinically effective than adalimumab and ustekinumab, and agreed it was likely that ixekizumab was similarly effective compared with secukinumab and infliximab while tolerability was similar to other biological treatments approved for treating psoriasis. The Evidence Review Group's critical assessment of the company's economic evaluation highlighted a number of concerns, including (1) the use of relative outcomes such as Psoriasis Area and Severity Index response to model the cost effectiveness; (2) the exclusion of the consequences of adverse events; (3) the assumption of no utility gain in the induction phase; (4) equal annual discontinuation rates for all treatments; (5) the selection of treatment sequences for consideration in the analyses and; (6) the transparency of the Visual Basic for Applications code used to develop the model. Although some of these issues were adjusted in the Evidence Review Group base case, the Evidence Review Group could not estimate the impact of all of these issues, and thus acknowledges that there are still uncertainties concerning the cost-effectiveness evidence. In the Evidence Review Group base-case incremental analysis, the treatment sequence incorporating ixekizumab in the second line has an incremental cost-effectiveness ratio of £25,532 per quality-adjusted life-year gained vs. the etanercept sequence. Ixekizumab in the first-line sequence has an incremental cost-effectiveness ratio of £39,129 per quality-adjusted life-year gained compared with the treatment sequence incorporating ixekizumab in the second line. Consistent with its conclusion regarding clinical effectiveness, the Appraisal Committee concluded that the cost effectiveness of ixekizumab for treating moderate-to-severe plaque psoriasis was similar to that of other biological treatments, already recommended in previous National Institute for Health and Care Excellence guidance. The committee concluded that the incremental cost-effectiveness ratio was within the range that could be considered a cost-effective use of National Health Service resources.

Secukinumab is the most efficient treatment for achieving clear skin in psoriatic patients: a cost-consequence study from the Spanish National Health Service.

OBJECTIVE: To compare the cost consequence of biologic drugs for moderate-to-severe psoriasis from the perspective of the Spanish National Health System. METHODS: We built a decision tree with a two-year time horizon. Efficacy data for biologics (etanercept, infliximab, adalimumab, ustekinumab and secukinumab) were drawn from published meta-analyses: PASI75 for the induction phase and PASI90 for the rest of follow-up. Patients with PASI < 75 at week 10-16 were switched to another biologic agent. Efficacy at week 24 was considered the highest possible efficacy for each drug and assumed to remain constant throughout the two-year period. Only drug treatment costs were used. The number needed to treat (NNT), annual cost per patient, annual cost per patient with PASI90 (cost per responder) and cost of primary failure (PASI < 75 at first efficacy evaluation) were calculated. RESULTS: Secukinumab monotherapy was associated with the lowest cost per responder, followed by infliximab and ustekinumab. Treatment sequences starting with secukinumab were the most efficient, having the lowest NNT and cost per responder. Although the annual cost per treatment is similar for all drugs, there are huge differences in the cost per responder. CONCLUSIONS: Secukinumab as first-line biologic treatment is the most efficient treatment for moderate-to-severe plaque psoriasis in the short-to-medium term.

Cost-utility analysis of certolizumab pegol in combination with methotrexate in patients with moderate-to-severe active rheumatoid arthritis in Greece.

We aimed to evaluate the cost-effectiveness of certolizumab pegol (CZP), a pegylated fc-free anti-TNF, as add-on therapy to methotrexate (MTX) versus etanercept, adalimumab, or golimumab in patients with moderate-to-severe active rheumatoid arthritis (RA) not responding to the conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). A Markov model (6-month cycle length) assessed health and cost outcomes of CZP versus other anti-TNFs recommended for RA in Greece over a patient's lifetime. Following discontinuation of first-line anti-TNF, patients switched to second anti-TNF and then to a biologic with another mode of action. Sequential use of csDMARDs followed third biologic. Clinical data and utilities were extracted from published literature. Analysis was conducted from third-party payer perspective in Greece. Costs (drug acquisition, administration, monitoring, and patient management) were considered for 2014. Results presented are incremental cost-effectiveness ratios (ICERs) per quality-adjusted life year (QALY). Probabilistic sensitivity analysis (PSA) ascertained robustness of base-case findings. Base-case analysis indicated that CZP+MTX was more costly and more effective compared with Etanercept+MTX (base-case ICER: €3,177 per QALY), whilst versus adalimumab/golimumab, CZP was dominant (less costly, more effective). For all comparisons, CZP treatment resulted in greater improvements in life expectancy and QALYs. PSA indicated that at the willingness-to-pay threshold of €34,000/QALY, CZP+MTX was associated with a 71.6, 97.9, or 99.2% probability of being cost-effective versus etanercept, golimumab, or adalimumab, respectively, in combination with MTX. This analysis demonstrates CZP+MTX to be a cost-effective alternative over Etanercept+MTX and a dominant option over Adalimumab+MTX and Golimumab+MTX for management of RA in Greece.

Cost-Effectiveness of Pembrolizumab Versus Ipilimumab in Ipilimumab-Naïve Patients with Advanced Melanoma in the United States.

BACKGROUND: Recent clinical trials have shown that pembrolizumab significantly prolonged progression-free survival and overall survival compared with ipilimumab in ipilimumab-naïve patients with unresectable or metastatic melanoma. However, there has been no published evidence on the cost-effectiveness of pembrolizumab for this indication. OBJECTIVE: To assess the long-term cost-effectiveness of pembrolizumab versus ipilimumab in ipilimumab-naïve patients with unresectable or meta-static melanoma from a U.S. integrated health system perspective. METHODS: A partitioned-survival model was developed, which divided overall survival time into progression-free survival and postprogression survival. The model used Kaplan-Meier estimates of progression-free survival and overall survival from a recent randomized phase 3 study (KEYNOTE-006) that compared pembrolizumab and ipilimumab. Extrapolation of progression-free survival and overall survival beyond the clinical trial was based on parametric functions and literature data. The base-case time horizon was 20 years, and costs and health outcomes were discounted at a rate of 3% per year. Clinical data-including progression-free survival and overall survival data spanning a median follow-up time of 15 months, as well as quality of life and adverse event data from the ongoing KEYNOTE-006 trial-and cost data from public sources were used to populate the model. Costs included those of drug acquisition, treatment administration, adverse event management, and disease management of advanced melanoma. The incremental cost-effectiveness ratio (ICER) expressed as cost difference per quality-adjusted life-year (QALY) gained was the main outcome, and a series of sensitivity analyses were performed to test the robustness of the results. RESULTS: In the base case, pembrolizumab was projected to increase the life expectancy of U.S. patients with advanced melanoma by 1.14 years, corresponding to a gain of 0.79 discounted QALYs over ipilimumab. The model also projected an average increase of $63,680 in discounted perpatient costs of treatment with pembrolizumab versus ipilimumab. The corresponding ICER was $81,091 per QALY ($68,712 per life-year) over a 20-year time horizon. With $100,000 per QALY as the threshold, when input parameters were varied in deterministic one-way sensitivity analyses, the use of pembrolizumab was cost-effective relative to ipilimumab in most ranges. Further, in a comprehensive probabilistic sensitivity analysis, the ICER was cost-effective in 83% of the simulations. CONCLUSIONS: Compared with ipilimumab, pembrolizumab had higher expected QALYs and was cost-effective for the treatment of patients with unresectable or metastatic melanoma from a U.S. integrated health system perspective. DISCLOSURES: This study was supported by funding from Merck & Co., which reviewed and approved the manuscript before journal submission. Wang, Pellissier, Xu, Stevinson, and Liu are employees of, and own stock in, Merck & Co. Chmielowski has served as a paid consultant for Merck & Co. and received a consultant fee for clinical input in connection with this study. Chmielowski also reports receiving advisory board and speaker bureau fees from multiple major pharmaceutical companies. Wang led the modeling and writing of the manuscript. Chmielowski, Xu, Stevinson, and Pellissier contributed substantially to the modeling design and methodology. Liu led the data collection work and contributed substantially to writing the manuscript. In conducting the analysis and writing the manuscript, the authors followed Merck publication polices and the "cost-effectiveness analysis alongside clinical trials-good research practices and the CHEERS reporting format as recommended by the International Society for Pharmacoeconomics and Outcomes Research.

Economics of ramucirumab for metastatic colorectal cancer.

INTRODUCTION: Despite its FDA approval and incorporation into the National Comprehensive Cancer Network (NCCN) treatment guidelines, ramucirumab (RAM) is associated with a drug acquisition cost that is substantially higher than other approved options. Given its substantial cost, the presence of a viable alternative treatment option, and its minimal survival improvement, the usefulness of RAM in clinical practice has been called into question. Areas covered: In this paper, we outline the cost, benefits, and economic implications of RAM from a US perspective, as it is used in the treatment of mCRC. We also dissect its use in other tumor types and in other healthcare systems around the world, and briefly compare it with similar drugs targeting the vascular endothelial growth factor pathway. We used the search engine PubMed using the following as search terms: cost-effectiveness; ramucirumab; metastatic colon cancer; angiogenesis; and value-based medicine. Expert commentary: The use of ramucirumab in the treatment of mCRC serves as a microcosm of the worsening healthcare crisis within the US and the ongoing controversy regarding oncology drug costs, benefits, and value. Therefore, there must be a joint effort in moving towards value based pricing models.

Longitudinal trends in use of targeted therapies for treatment of malignant neoplasms of the eye: a population-based study in Taiwan.

OBJECTIVES: This study examined the recent trend in use and costs of antineoplastic agents for treatment of eye malignancies in Taiwan from 2009 to 2012. We also forecasted use and costs of targeted therapies up to and including year 2016 based on the current patterns. DESIGN: Retrospective observational study focusing on the usage of targeted therapies for treatment of eye malignancy. SETTING: The monthly claims data for eye malignancy-related antineoplastic agents were retrieved from Taiwan's National Health Insurance Research Database (2009-2012). MAIN OUTCOME MEASURES: We calculated the number of prescriptions and costs for each class of medications, and analysed their time trends. In addition, using a time series design with ARIMA models, we estimated the market share by prescription volume and the proportion of costs for targeted therapies for year 2016. RESULTS: The market share by prescription volume of targeted therapies grew from 1.56% in 2009 to 9.98% in 2012 among all antineoplastic agents, and the proportion of costs for targeted therapies rose from 15.12% in 2009 to 58.88% in 2012. Especially, the proportion of costs for protein kinase inhibitors grew from 25.62% to 45.28% among all antineoplastic agents between 2010 and 2012. The market share by prescription volume and the proportion of costs for targeted therapies for treatment of eye malignancies were predicted to reach 27.33% and 91.39% by the fourth quarter in 2016, respectively. CONCLUSIONS: This is the first study that examined and forecasted use and costs of targeted therapies for treatment of eye malignancies in Taiwan. Our findings indicate that, compared with other classes of drugs, targeted therapies are having a more and more relevant share among all treatment strategies for eye malignancies in Taiwan, and due to their high costs they are likely to cause great economic burden.

Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers.

Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the detailed advantages and disadvantages of antibodies and aptamers in therapeutic applications and summarize recent progress in aptamer selection and modification approaches. We will present therapeutic oligonucleotide aptamers in preclinical studies for skeletal diseases and further discuss oligonucleotide aptamers in different stages of clinical evaluation for various disease therapies including macular degeneration, cancer, inflammation and coagulation to highlight the bright commercial future and potential challenges of therapeutic oligonucleotide aptamers.

Clinical and economic review of secukinumab for moderate-to-severe plaque psoriasis.

Secukinumab represents the first IL-17A antagonist among the available biologic therapies approved for moderate-to-severe plaque psoriasis management. Secukinumab demonstrated greater efficacy over placebo, etanercept and ustekinumab in patients that had limited benefit from non-biologic systemic therapies and phototherapy. Despite standard-of-care systemic therapies being more likely to be cost-effective at this time, a Canadian cost-utility analysis found secukinumab to display benefit in quality-of-life gains in moderate-to-severe plaque psoriasis patients, and greater cost-effectiveness when compared to other biologic systemic therapies. Determination of the true economic value of secukinumab amongst the available therapies for moderate-to-severe plaque psoriasis will require continued economic evaluation.

Estimated cost efficacy of systemic treatments that are approved by the US Food and Drug Administration for the treatment of moderate to severe psoriasis.

BACKGROUND: Newer psoriasis treatments tout higher efficacy but are generally more expensive. OBJECTIVE: We sought to estimate the cost efficacy of systemic psoriasis treatments that have been approved by the US Food and Drug Administration (FDA). METHODS: A literature review of systemic psoriasis treatments that have been approved by the FDA was performed for the primary end point of a 75% reduction in the Psoriasis Area and Severity Index score (PASI 75). Medication cost was referenced by wholesale acquisition cost (WAC), laboratory fees were obtained from the American Medical Association, and office visit fees are standard at our university. Total expenses were standardized by calculating cost per month of treatment considering the number needed to treat (NNT) to achieve PASI 75. RESULTS: Methotrexate ($794.05-1502.51) and cyclosporine ($1410.14-1843.55) had the lowest monthly costs per NNT to achieve PASI 75. The most costly therapies were infliximab ($8704.68-15,235.52) and ustekinumab 90 mg ($12,505.26-14,256.75). Monthly costs per NNT to achieve PASI 75 for other therapies were as follows: narrowband ultraviolet B light phototherapy ($2924.73), adalimumab ($3974.61-7678.78), acitretin ($4137.71-14,148.53), ustekinumab 45 mg ($7177.89-7263.99), psoralen plus ultraviolet A light phototherapy ($7499.46-8834.98), and etanercept ($8284.71-10,674.89). LIMITATIONS: Drug rebates and incentives, potential adverse effects, comorbidity risk reduction, ambassador programs, and combination therapies were excluded. CONCLUSION: Our study provides meaningful cost efficacy data that may influence psoriasis treatment selection.

[Evolution of biologicals in inflammation medicine--biosimilars in gastroenterology, rheumatology and dermatology]. / Evolution der Biologika in der Entzündungsmedizin--Biosimilars in Gastroenterologie, Rheumatologie und Dermatologie.

Biologicals revolutionized the therapy of chronic inflammatory diseases in gastroenterology, rheumatology and dermatology in the last decade. The first generation biologicals mainly targeted against the pro-inflammatory cytokine TNF-α. The evolution of these therapies in the last years led to the development of new antibodies and to the admission of first generation "generic" biologics - the biosimilars. Biosimilars are not a fundamental new pharmacological development for existing substances, however they have the potential to lead to enormous cost savings in healthcare without reducing the level of care for patients. Biosimilars are not identical with the originator, but in an extensive biosimilarity exercise including analytical, preclinical and comparative clinical studies it was shown that the biosimilars could demonstrate comparability in all relevant aspects with the originator.In September 2013, the Infliximab biosimilars (Inflectra(®), Remsina(®)) were the first biosimilars for monoclonal antibodies to be authorized by the EMA for use in the European Union. By demonstrating the therapeutic similarity only in one indication (rheumatoid arthritis) the EMA agreed with an extrapolation also to all approved indications of the originator. This could be a relevant problem in clinical practice. Therefore, comparative studies with the originator are required in all approved indications.After expiration of the national patent protection in beginning of 2015, the infliximab biosimilars will be launched on the market in Germany and will be part of the therapeutic arsenal in gastroenterology, rheumatology and dermatology. Interchangeability (Switching) of biosimilars with the originator will be subject of an important discussion with the health care providers. Regardless of the biosimilars EMA-approval, several potential problems (efficacy, extrapolation, switching, long-term safety) should be the topic of intensive long-term registries in the future.

Economical impact associated with a biological therapy prioritization protocol in patients with rheumatoid arthritis in the Hospital of Sagunto.

BACKGROUND: Until 2010 the cost of biological treatments in Rheumatoid Arthritis (RA) was increasing annually by 15% in our hospital. In 1st January 2011, a Hospital Commission of Biological Therapies involving rheumatology and pharmacy services was created to improve the management of biological drugs and a biological therapy prioritization protocol in RA patients was also established to improve the efficient usage of biological drugs in RA. OBJECTIVE: To evaluate the economic impact associated with a biological therapy prioritization protocol for RA patients in the Hospital of Sagunto. METHODS: Observational, ambispective study comparing the associated cost of RA patients treated with biological drugs in the pre-protocol (2009 - 2010) versus post-protocol periods (2011 - 2012). RA patients treated with Abatacept (ABA), Adalimumab (ADA), Etanercept (ETN) or Infliximab (IFX) for at least 6 months during the study period (2009 - 2012) were included. In 2012, Tocilizumab (TCZ) was also included in the prioritization protocol. Prioritization protocol was established based on both clinical and economical aspects and supervised case by case by our Commission. Cost savings and economic impact were calculated using Spanish official prices. RESULTS: In the pre-protocol period (2009 - 2010), total expenses were increasing by €110,000, up to €1,761,000 in 2010 (€11,362 pat/year). After protocol implementation, total expenses decreased by 53,676€ on the 2010 - 2011 period, and 149,200€ on the 2011 - 2012 period. On the 2010 - 2011 period the cost of biological therapy per patient-year decreased 355€ (11,007€ pat/year) and additional 653€ (up to 10,354€ pat/year) by 2012, with a cumulative effect of the protocol implementation of 1,008€ per patient-year. In the pre-protocol period (2009), the annual cost/patient was 10.812€ with ETN, 10.942€ with IFX, 12.961€ with ADA and 12.739€ with ABA. By 1st January 2013, the annual cost per patient was 9,469€ with ETN, 10,579€ with IFX, 11,117€ with ADA, 13,540€ with ABA and 14,932€ with TCZ. CONCLUSIONS: The creation of our Commission of Biological Therapies is key to rational management of RA patients and optimization of resources, allowing us to save 200,000€ after 2-year efficiency protocol implementation.

Cost-effectiveness analysis of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

OBJECTIVE: To investigate the cost-effectiveness of panitumumab plus mFOLFOX6 (oxaliplatin, 5-fluorouracil and leucovorin) compared with bevacizumab plus mFOLFOX6 in first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC). DESIGN: A semi-Markov model was constructed from a French health collective perspective, with health states related to first-line treatment (progression-free), disease progression with and without subsequent active treatment, resection of metastases, disease-free after successful resection and death. METHODS: Parametric survival analyses of patient-level progression-free and overall survival data from the only head-to-head clinical trial of panitumumab and bevacizumab (PEAK) were performed to estimate transitions to disease progression and death. Additional data from PEAK informed the amount of each drug consumed, duration of therapy, subsequent therapy use, and toxicities related to mCRC treatment. Literature and French public data sources were used to estimate unit costs associated with treatment and duration of subsequent active therapies. Utility weights were calculated from patient-level data from panitumumab trials in the first-, second- and third-line settings. A life-time perspective was applied. Scenario, one-way, and probabilistic sensitivity analyses were performed. RESULTS: Based on a head-to-head clinical trial that demonstrates better efficacy outcomes for patients with wild-type RAS mCRC who receive panitumumab plus mFOLFOX6 versus bevacizumab plus mFOLFOX6, the incremental cost per life-year gained was estimated to be €26,918, and the incremental cost per quality-adjusted life year (QALY) gained was estimated to be €36,577. Sensitivity analyses indicate the model is robust to alternative parameters and assumptions. CONCLUSIONS: The incremental cost per QALY gained indicates that panitumumab plus mFOLFOX6 represents good value for money in comparison to bevacizumab plus mFOLFOX6 and, with a willingness-to-pay ranging from €40,000 to €60,000, can be considered cost-effective in first-line treatment of patients with wild-type RAS mCRC.

[The cost study of first- line treatment of metastatic colorectal carcinoma with bevacizumab- containing regimen in the Czech Republic]. / Analýza nákladu na 1. linii lécby metastatického kolorektálního karcinomu pri podání rezimu s bevacizumabem -  data z reálné klinické praxe v Ceské republice.

BACKGROUND: Bevacizumab, a humanized monoclonal IgG antibody against the vascular endothelial growth factor (VEGF), is reimbursed in combination with chemotherapy for the first and subsequent line treatment of patients with metastatic colorectal cancer (mCRC) in the Czech Republic. However, its high cost is a potentially limiting factor. We assessed the cost of bevacizumab in the treatment of mCRC in a comprehensive cancer center. PATIENTS AND METHODS: A total of 218 patients were included in our analysis. Cost data (examination, medication, hospitalization) were collected since the initiation of bevacizumab treatment to any tumor response (RECIST criteria: complete response -  CR, partial response -  PR, stable disease -  SD, progressive disease -  PD) and/ or to death. Minimal followup for all patients was 28 months. Costs were valued in Czech crowns (CZK) and converted to EUR (1€ = 25.14 CZK). RESULTS: PD was recorded in 194 patients (89% of patients). The mean cost of treatment to PD (median TTP 9.1 months) was 1,002,076.30 CZK (39,859.84 EUR). The majority of costs to PD was made by medication -  917,048.60 CZK (36,477.67 EUR) per patient. The mean cost to response PR, CR or SD was 1,105,823.10 CZK (43,986.60 EUR) after median 9.8 months of treatment (recorded for 21 patients), medication formed 1,023,827.70 CZK (40,725.05 EUR). During the study, 170 patients (78%) died. The mean of the total costs since initiation of treatment to death (median OS 18.8 months) was 1,338,874.20 CZK (53,256.70 EUR) -  out of that, medication was 1,184,251.10 CZK (47,106.25 EUR) per patient. CONCLUSION: Targeted bio-logical therapy is the largest part of the costs of mCRC therapy. Cost of bevacizumab made up to 69% of costs to PD -  687,608.20 CZK ( 27,351.20 EUR ) per patient. The majority of the total cost was formed by targeted drug therapy (bevacizumab in 1st line therapy, cetuximab and panitumumab in 2nd and 3rd line therapy); 58% of total costs since initiation of treatment to death -  778,233.80 CZK (30,956 EUR) per patient.