1,721,282 research outputs found
From "blockbusters" to "biosimilars": An opportunity for patients, medical specialists and health care providers
No full textAdvances in basic research and research and development plans of pharmaceutical companies are radically changing the kind of available drugs and therapeutic targets. We are switching from predominantly chemical molecules, aimed at treating large populations of patients (blockbuster drugs), to a new generation of products, mostly biotech, aimed at modifying a specific pathogenetic mechanism. In other word we are moving fast to targeted therapy, which represents the first step toward personalized therapy, where the right drug at the right dose is administered to the right person, at the right time. Like the patent expiration of chemical products has corresponded to the development of generic drugs, the expiration of new biotech products will witness the appearance of biosimilars. The latter are biologic products that are highly similar but not identical to the reference medical products in terms of quality, safety and efficacy. This implies specific research, clinical monitoring, physicians updating of knowledge for a safe and appropriate use of these products. We are the beginning of a devolution in patient's care and physicians' practice. © 2012 Elsevier Ltd
AIT (allergen immunotherapy): a model for the “precision medicine”
No full textThe interpretation of medical approaches, especially therapy, evolved rapidly in the last century. Starting from the simple description of symptoms, we moved to the pathophysiological descriptions, to the evidence-based medicine, until the so-called "precision medicine". This latter can be defined as a structural model aimed at customizing healthcare, with medical decisions/products tailored on an individual patient at a highly detailed level. In this sense, allergen immunotherapy represents an optimal model of "precision medicine", since we know and describe symptoms, function, aetiological agents at molecular level, and we have the possibility to intervene on the natural history of the disease. If considered under the point of view of pharmaco-economy, that is prescribing the optimal treatment to the right patient, allergen immunotherapy represents an almost-ideal model of precision medicine
Clinically significant differences in patient-reported outcomes evaluations in chronic spontaneous urticaria
No full textPurpose of review The aim of this review is to highlight the conceptual and practical knowledge for interpreting score changes in patient-reported outcomes (PROs) that have been validated for chronic spontaneous urticaria (CSU). Recent findings The urticaria guidelines recommends to assess PROs as Health-Related Quality of Life, disease activity and disease control, to detect the CSU impact and the overall treatment effect. To this aim it is crucial to determine the minimal important difference (MID) to assess if changes in questionnaire scores represent either perceived improvement or deterioration for patients. Methods for establishing the MID are well defined and are clustered into two broad categories: distribution-based and anchor-based. Summary For the majority of the available questionnaires for CSU, an MID has been defined, according to the results of various approaches. In most of the studies in our review, anchor-based methods, either alone or in combination with distribution ones, were used. The available information regarding MIDs across validated tools for CSU patients helps to interpret measurement scores and allows the implementation of PROs in routine practices
Type 2 immunity in asthma
No full textType 2-immunity represents the typical adaptive response to allergen exposure in atopic individuals. It mainly involves Th2 cells and immunoglobulin E, as the main orchestrators of type 2-inflammation. Recently, it has been highlighted that allergens may be responsible for a Th2 response beside specific IgE activation and that a number of other environmental stimuli, such as viruses and pollutants, can trigger the same pattern of inflammation beyond atopy. Emerging data sustain a substantial role of the so-called epithelial dysfunction in asthma pathogenesis, both from anatomic and functional point of view. Furthermore an increasing amount of evidence demonstrates the relevance of innate immunity in polarizing a Th2 impaired response in asthmatic patients. Under this perspective, the complex cross-talking between airway epithelium, innate and adaptive immunity is emerging as a major determinant of type 2-inflammation beyond allergens. This review will include an update on the relevance of dysregulation of innate and adaptive type 2-immunity in asthma pathogenesis, particularly severe asthma, and on the role of the allergens that are associated with severe asthma. Type 2-immunity also will be reviewed in the light of the current and upcoming targeted treatments for severe asthma
Allergen immunotherapy in asthma; what is new?
No full textThe use and role of allergen immunotherapy (AIT) in asthma is still a matter of debate, and no definite recommendation about this is made in guidelines, both for the subcutaneous and sublingual routes. This is essentially due to the fact that most controlled randomised trials were not specifically designed for asthma, and that objective measures of pulmonary function were only occasionally considered. Nonetheless, in many trials, favourable results in asthma (symptoms, medication usage, bronchial reactivity) were consistently reported. There are also several meta analyses in favour of AIT, although their validity is limited by a relevant methodological heterogeneity. In addition to the crude clinical effect, a disease modifying action of AIT (prevention of asthma onset and long-lasting effects) have been reported. The safety is an important aspect to consider in asthma. Fatalities were rare: In Europe no fatality was reported in the last three decades, as in the United States in the last 4 years. Based on previous surveys, and common sense, uncontrolled asthma is still recognized as the most important risk factor for severe adverse events. On the contrary, there is no evidence that AIT can worsen or induce asthma. According to the available evidence, AIT can be safely used as add-on treatment when asthma is associated with rhinitis (a frequent condition), provided that asthma is adequately controlled by pharmacotherapy. AIT cannot be recommended or suggested as single therapy. When asthma is the unique manifestation of respiratory allergy, its use should be evaluated case by case
Personalized medicine and allergen immunotherapy: the beginning of a new era?
No full textThe concept of personalized medicine as a diagnostic and therapeutic approach tailored to the medical needs of each patient is currently revolutionizing all fields of medicine and in particular allergology. Allergen immunotherapy (AIT) meets the three main needs for precision medicine: identification of molecular mechanism of disease, diagnostic tools for the mechanism and treatment blocking the mechanism itself. AIT adapts to the spectrum of specific IgE of each individual subject, changing the course and natural history of the disease, so is a clear model of precision and personalized medicine. This first step before the prescription of AIT is to define the sensitization profile of the patient; after that, the healthcare professional has numerous levers for adapting the treatment to the physio-pathological mechanisms involved. AIT allows to adapt treatments to the profile of the patients, but also to the its preferences, to ensure optimal treatment efficacy, resulting in an agile and personalized approach, with the aim to ensure adherence to the treatment, which is usually quite low. AIT also broadens the field of possibilities for healthcare professionals and patients, by allowing to choose the galenic formulation according to patient preferences and on the basis of their clinical history, adapting the product composition to the patient’s sensitization profiles and the underlying biological mechanisms identified at the diagnostic stage, while guaranteeing quality of the prescribed product as the production of allergens and allergoids is today more regulated than in the past years. In the management of AIT, it is also possible to involve patients in decisions throughout their care pathway thanks to multiple services, offering personalized follow-up and support, to ensure the highest treatment efficacy levels, and recalling medication intake, medical appointments and prescription renewals
Determinants of response to inhaled extrafine triple therapy in asthma: analyses of TRIMARAN and TRIGGER
No full textBackground: A number of single-inhaler triple therapies are being developed for asthma, including the extrafine formulation of beclometasone dipropionate (BDP), formoterol fumarate (FF), and glycopyrronium (G). Given asthma is a heterogenous disease, we investigated whether the clinical response to the addition of the long-acting muscarinic antagonist component within inhaled triple therapy was impacted by a range of clinical characteristics. Methods: These were pre-specified and post-hoc sub-group analyses of TRIMARAN and TRIGGER, which were double-blind, 52-week studies comparing medium-strength (100/6/10 μg; TRIMARAN) and high-strength (200/6/10 μg; TRIGGER) BDP/FF/G with the respective BDP/FF strengths in adults with uncontrolled asthma and a history of ≥ 1 exacerbation. Co-primary endpoints were pre-dose forced expiratory volume in 1 s (FEV1) at Week 26 and the rate of moderate-to-severe exacerbations over 52 weeks. Key secondary endpoints: peak FEV1 at Week 26 and average morning peak expiratory flow over the first 26 weeks in each study, and severe exacerbation rate over 52 weeks (pooled data). Results: Baseline clinical characteristics (pre-specified analyses) had no consistent effect on the lung function improvements with BDP/FF/G. For the exacerbation endpoints, sub-groups with higher reversibility gained greatest relative benefit from BDP/FF/G versus BDP/FF. In post-hoc analyses with patients sub-grouped by screening blood eosinophil values, in TRIMARAN the greatest relative effect of BDP/FF/G versus BDP/FF on the lung function endpoints was in the ≤ 300 cells/μL group; in TRIGGER, eosinophil levels did not markedly influence the relative efficacy of BDP/FF/G versus BDP/FF. Eosinophil levels did not influence relative efficacy on moderate-to-severe or severe exacerbations. Conclusion: Overall, the relative efficacy of extrafine BDP/FF/G versus BDP/FF was not influenced by a range of clinical characteristics. However, some patient sub-groups gained additional benefit from BDP/FF/G for certain endpoints. In particular, for exacerbations the relative efficacy of BDP/FF/G was greater in more reversible patients. Trial registration ClinicalTrials.gov: TRIMARAN, NCT02676076 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676076?term=NCT02676076&draw=2&rank=1,); TRIGGER, NCT02676089 (registered February 8, 2016, https://clinicaltrials.gov/ct2/show/NCT02676089?term=NCT02676089&draw=2&rank=1)
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