Abstract:BackgroundThis study evaluated the effect of early anti-tumor necrosis factor (TNF) therapy in patients with severe rheumatoid arthritis (RA) on the subsequent risk of total knee replacement (TKR) surgery.MethodsThis retrospective observational study included a hospital-based cohort of 200 patients diagnosed with severe RA who received treatment with anti-TNF therapy between 2003 and 2014. Clinical parameters including age, sex, body mass index, and the time from the diagnosis of RA to the initiation of anti-T… Show more
“…Although the introduction of biologics has increased direct healthcare costs for IMIDs, their potential impact on indirect costs and on other medical costs, such as hospitalization and surgery, is also an important consideration. For example, use of biologics can reduce the rate of expensive surgical interventions in RA and IBD (Moura et al, 2015; Chen et al, 2017; Mao et al, 2017). Furthermore, the improved quality of life associated with biologic therapy can increase productivity and reduce the societal impact of RA (Strand and Singh, 2010), and earlier access to biologics for RA patients has been shown to have a positive effect on employment status (Olofsson et al, 2017).…”
Section: Economic Impact Of Immune-mediated Inflammatory Diseasesmentioning
Biological therapies are an effective treatment for a range of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, psoriasis, and inflammatory bowel diseases. However, due to their high costs, considerable differences in their utilization exist across the world, even among the various European countries, with many countries restricting access despite professional society guideline recommendations. Adoption of biologics by healthcare providers has been particularly poor in many Central and Eastern European countries. Differences in utilization have also been observed across medical specialties, healthcare providers, and at a regional and national level. The objective of this paper is to provide an overview of the different market access policies for biologics in Europe and to investigate reasons for such differences. One of the potential solutions for providing broader access to IMID patients, where cost is the major barrier, is to encourage the use of biosimilars in place of their reference products. Biosimilars are generally less expensive alternatives to already licensed biological therapies and are approved on the basis that they are similar to the reference product in terms of quality, safety, and efficacy. Budget impact models predict considerable cost savings following the introduction of biosimilars in the next few years. These savings could be used to increase access to biologics and other innovative therapies.
“…Although the introduction of biologics has increased direct healthcare costs for IMIDs, their potential impact on indirect costs and on other medical costs, such as hospitalization and surgery, is also an important consideration. For example, use of biologics can reduce the rate of expensive surgical interventions in RA and IBD (Moura et al, 2015; Chen et al, 2017; Mao et al, 2017). Furthermore, the improved quality of life associated with biologic therapy can increase productivity and reduce the societal impact of RA (Strand and Singh, 2010), and earlier access to biologics for RA patients has been shown to have a positive effect on employment status (Olofsson et al, 2017).…”
Section: Economic Impact Of Immune-mediated Inflammatory Diseasesmentioning
Biological therapies are an effective treatment for a range of immune-mediated inflammatory diseases (IMIDs), including rheumatoid arthritis, psoriasis, and inflammatory bowel diseases. However, due to their high costs, considerable differences in their utilization exist across the world, even among the various European countries, with many countries restricting access despite professional society guideline recommendations. Adoption of biologics by healthcare providers has been particularly poor in many Central and Eastern European countries. Differences in utilization have also been observed across medical specialties, healthcare providers, and at a regional and national level. The objective of this paper is to provide an overview of the different market access policies for biologics in Europe and to investigate reasons for such differences. One of the potential solutions for providing broader access to IMID patients, where cost is the major barrier, is to encourage the use of biosimilars in place of their reference products. Biosimilars are generally less expensive alternatives to already licensed biological therapies and are approved on the basis that they are similar to the reference product in terms of quality, safety, and efficacy. Budget impact models predict considerable cost savings following the introduction of biosimilars in the next few years. These savings could be used to increase access to biologics and other innovative therapies.
“…Importantly, peripheral arthritis remains radiologically stable in AxSpA patients under infliximab, especially in the hip [ 39 ], resulting also in reduced hip replacement surgery rate [ 40 , 41 ]. Through ameliorating inflammatory joint destruction, anti-TNF-α therapy led to 40% reduction of joint replacement surgery in older RA patients [ 42 ], while the benefit was stronger when treatment was introduced early in the disease course [ 43 ]. Fig.…”
Since the late 1990s, tumor necrosis factor alpha (TNF-α) inhibitors (anti-TNFs) have revolutionized the therapy of immune-mediated inflammatory diseases (IMIDs) affecting the gut, joints, skin and eyes. Although the therapeutic armamentarium in IMIDs is being constantly expanded, anti-TNFs remain the cornerstone of their treatment. During the second decade of their application in clinical practice, a large body of additional knowledge has accumulated regarding various aspects of anti-TNF-α therapy, whereas new indications have been added. Recent experimental studies have shown that anti-TNFs exert their beneficial effects not only by restoring aberrant TNF-mediated immune mechanisms, but also by de-activating pathogenic fibroblast-like mesenchymal cells. Real-world data on millions of patients further confirmed the remarkable efficacy of anti-TNFs. It is now clear that anti-TNFs alter the physical course of inflammatory arthritis and inflammatory bowel disease, leading to inhibition of local and systemic bone loss and to a decline in the number of surgeries for disease-related complications, while anti-TNFs improve morbidity and mortality, acting beneficially also on cardiovascular comorbidities. On the other hand, no new safety signals emerged, whereas anti-TNF-α safety in pregnancy and amid the COVID-19 pandemic was confirmed. The use of biosimilars was associated with cost reductions making anti-TNFs more widely available. Moreover, the current implementation of the “treat-to-target” approach and treatment de-escalation strategies of IMIDs were based on anti-TNFs. An intensive search to discover biomarkers to optimize response to anti-TNF-α treatment is currently ongoing. Finally, selective targeting of TNF-α receptors, new forms of anti-TNFs and combinations with other agents, are being tested in clinical trials and will probably expand the spectrum of TNF-α inhibition as a therapeutic strategy for IMIDs.
background:
Rheumatoid arthritis (RA) is a systemic inflammatory disease in which TNF-α plays an important role. Fibroblast growth factor receptor 3 (FGFR3) is reportedly involved in RA by regulating expression of inflammatory cytokines.
objective:
This study examined the expression profile of FGFR3 in human synovial biopsy tissues and evaluated its gene silencing effects on behaviors of synovial cells.
method:
Immunohistochemical staining was used to measure FGFR3 expression in human RA joint tissues. Cell proliferation, migration, and apoptosis assays were used to monitor behavioral changes in cultured synovial SW-982 cells with siRNA-mediated FGFR3 gene silencing. Immunofluorescent staining and western blotting were used to detect molecular changes in the FGFR3 gene silenced cells.
result:
FGFR3 up-regulation was noted in both cytoplasms and nuclei of synovial cells in human RA joints. FGFR3 siRNA delivery experiments corroborated that FGFR3 knockdown decreased proliferation and migration, and triggered apoptosis of synovial cells. The FGFR3 gene knockdown enhanced constitutive expression of epithelial marker E-cadherin and conversely suppressed expression of epithelial-mesenchymal transition (EMT) markers, including Snail, fibronectin and vimentin. In addition, FGFR3 silencing significantly reduced the constitutive expressions of TNF-α, transcription factor NF-kB, and downstream COX-2 protein and collagenolytic enzyme MMP-9. MAPK inhibition markedly suppressed constitutive levels of NF-kB, COX-2 and MMP-9.
conclusion:
Genetic interference of FGFR3 could modulate the expression of inflammatory mediators and EMT markers in the synovial cells. Targeting FGFR3/MAPK signal axis may be considered as a useful therapeutic strategy to ameliorate the development of RA.
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