1,721,230 research outputs found
Biosimilars in rheumatology: pharmacological and pharmacoeconomic issues
No full textRheumatoid arthritis (RA) societal costs are high because the disease may cause not only restricted joint mobility, chronic pain, fatigue, and functional disability, but also psychological distress. Direct health care costs represent about one-fourth of all costs and are prevalently represented by in-patient care expenditures. The introduction of biologics disease-modifying anti-rheumatic drugs (B-DMARDs), has really changed the perspectives of the patients not fully responding to conventional DMARDs, but the direct costs for drugs has really modified the expenditure for this disease and many other diseases, i.e. psoriatic arthritis, spondyloarthropathies. Increasing pressure for lower cost versions of biological medicines, the scientific technology (particularly analytical technology) that continues to improve will lead to the introduction through reverse ingeneering of biosimilar drugs in rheumatology. The hope is to provide cost savings, which may broaden access to biopharmaceuticals and stimulate further research. The need for patients to have a biosimilar product, with comparable efficacy and safety, will be discussed in this paper along with all the possible issues that will govern the assessment of the bioequivalence and of the interchangeability
[Class IV-G and IV-S lupus nephritis, interstitial infiltrates and prognosis: state of the art and unmet medical needs]
No full textNephritis in systemic lupus erythematosus is one of the manifestations of organ damage in this autoimmune disease. Class IV is the most ominous among the classes of nephritides and there are conflicting reports on whether class IV-G lupus nephritis differs from class IV-S as defined by the International Society of Nephrology and the Renal Pathology Society (ISN/RPS) in terms of kidney and patient survival. There is, however, general agreement that 15-30% of patients with class IV nephritis do not reach remission and that a similar percentage (15-30%) of those reaching remission relapses. The presence of interstitial nephritis may be one of the determinants of a poor disease course. In fact, in recent years new data have emerged regarding the role of interstitial infiltrates in determining a poor outcome, but until now no data have been gathered on the differentiation of outcomes among class IV-G or IV-S with and without infiltrates
The potential role of Th17 in mediating the transition from acute to chronic autoimmune inflammation: rheumatoid arthritis as a model.
No full textT helper 17 cells (Th17) have arisen in the last 15 years as major effector cells in several chronic inflammatory states. In synovitis associated with rheumatoid arthritis (RA), Th17 emerged as being involved in driving the active acute phases and correlated with local and systemic parameters of inflammation; in particular, TCRζ(dim) Th17 appear to be the greatest producers of IL-17 at the single-cell level. IL-1beta and IL-6, along with IL-23, arose as the major drivers of differentiation and local development of Th17, while IL-15 and cell-cell contact can trigger the local production of IL-17. TNF-alpha inhibition can reversibly block the migration of pathogenic effector memory TCRzeta(dim) T cells and CCR6+ Th17 from peripheral blood to inflamed tissues. IL-17 is a potent chemoattractant for pre-committed CD4+ T cells and neutrophils, and may promote the migration of B cells to lymphoid follicles in the chronic phase of synovial inflammation. Importantly, IL-17 drives osteoclastogenesis and neoangiogenesis in the RA joint. These data strongly suggest that Th17 are key effector cells in driving the transition from the acute to the chronic phase of RA inflammation
Should we consider tumor necrosis factor as the only target in spondyloarthritides?
No full textUnderstanding the biology of inflammation occurring at the entheseal-bone insertion has led to a better knowledge of the main drivers of inflammation in spondyloarthropathies. The clinical efficacy of tumor necrosis factor-α (TNF-α) blockers strongly supports the idea that TNF-α is a key molecule. Yet 40% of patients do not respond appropriately, indicating that other pathways are likely involved in these illnesses. Targeting T cells through a blockade of costimulating (CD28) molecules does not help, and in experimental models of sacroiliitis, targeting interleukin 6 (IL-6) did not provide any useful evidence. Immunohistological and functional data suggest that B cells, Th17, or IL-17A might be important, and indeed preliminary data concerning drugs targeting B cells and IL-17A seem to suggest clinical benefits
Optimizing outcomes in rheumatoid arthritis patients with inadequate responses to disease-modifying anti-rheumatic drugs
No full textConventional DMARDs such as MTX are the mainstay of treatment for patients with RA. However, failure to achieve adequate disease control in many patients, even with combination therapy, has spurred the development of agents that target various immune mediators involved in the disease process. In the past decade, biologic agents have proved viable as alternative or add-on therapy to DMARDs in patients whose disease is inadequately controlled. Well-controlled clinical trials have evaluated the effects of these agents not only on disease activity, but also on inhibition of structural change and improvement in physical function. This article reviews phase 3 clinical trial results on biologic agents that inhibit T- and B-cell activation (abatacept and rituximab, respectively), inflammatory cytokines such as TNF-α (adalimumab, etanercept, infliximab, golimumab and certolizumab) and IL-6 (tocilizumab). Although data comparing the efficacy of the various biologic agents are limited, the availability of biologic therapies with differing mechanisms of action expands therapeutic options for patients whose disease is inadequately controlled with DMARDs and allows for greater individualization of treatment
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