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ID PMID Title PublicationDate abstract
29287589 Rapid clinical improvement of amyloid A amyloidosis following treatment with tocilizumab d 2017 Dec 29 BACKGROUND: Amyloid A amyloidosis is one of the most common forms of amyloidosis. It is secondary to rheumatoid arthritis, which is difficult to manage and has a poor prognosis. We present a patient with rheumatoid arthritis and amyloid A amyloidosis who was treated with tocilizumab, a humanized monoclonal antibody against interleukin 6 receptor, resulting in improvement in both proteinuria and gastrointestinal symptoms; however, amyloid deposition remained. CASE PRESENTATION: A 67-year-old woman who had previously been treated for rheumatoid arthritis presented with abdominal pain and diarrhea. Right renal cell carcinoma was found, and amyloid A amyloidosis was diagnosed concomitantly based on colon biopsy. The renal cell carcinoma was resected, and the non-cancerous part of the renal tissue also showed amyloid A deposition. Following surgery, protein levels in the urine increased to the nephrotic range, and administration of tocilizumab was initiated, which resulted in resolution of the proteinuria. The patient's gastrointestinal symptoms were also alleviated. However, repeat colon biopsy showed amyloid deposition. CONCLUSIONS: This case of amyloid A amyloidosis suggests that amyloid deposition indicates only structural change of the affected tissue, and that it is not amyloid deposition per se that causes the clinical symptoms of amyloidosis.
28386136 Assessment of anti-CarP antibodies, disease activity and quality of life in rheumatoid art 2017 OBJECTIVE: Good biomarkers are important to guide decisions in the clinical management of rheumatoid arthritis (RA). RA patients harbor antibodies directed against carbamylated proteins which may predict joint damage. This study investigated whether antibodies against carbamylated proteins (anti-CarP) may serve as surrogate prognostic markers. MATERIAL AND METHODS: Fifty-three patients with a diagnosis of rheumatoid arthritis according to ACR 1987 criteria were included. Blood samples were analyzed for CarP antibody levels using the ELISA method. Quality of life (QoL) was assessed by the WHO SF-36 questionnaire, and disease activity was assessed using the DAS28 calculator. Newly diagnosed patients were assessed at the first visit and at 12 weeks of treatment, while a single assessment was made for patients already on maintenance therapy. RESULTS: Out of 53 patients, 22 had titers of anti-CarP above the cut-off range and considered as positive for anti-CarP antibodies. Anti-CarP antibody serum level was significantly higher in patients with deformity of joints and with erosions in comparison to those without any destructive changes (p < 0.05). There was a weak positive correlation between anti-CarP and DAS 28 (p > 0.05). Also there was a weak negative correlation in all domains of quality of life with anti-CarP antibody titers (p > 0.05). There was no significant correlation between titers of anti-CarP antibodies and presence or absence of rheumatoid factor. CONCLUSIONS: Serum levels of anti-CarP antibodies in RA patients with joint erosions/deformities were much higher than in those without any joint damage. Anti-CarP antibodies may have good prognostic value in RA patients with erosions. Disease activity and QoL of RA patients improved during treatment, but no correlation was found between DAS 28/QoL and anti-CarP antibody serum levels.
28804234 Nitric Oxide: Link between Inflammation and Endothelial Dysfunction in Rheumatoid Arthriti 2017 Sep Nitric oxide (NO) plays an important role in inflammatory joint disease and endothelial function. Endothelial dysfunction has been attributed to a reduction in NO bioactivity in rheumatoid arthritis (RA). However, the relationship of NO with inflammation and endothelial dysfunction in RA has not yet been investigated. To investigate the relationship of nitrite with inflammation and endothelial dysfunction in RA. Total 28 patients satisfying 2010 Rheumatoid Arthritis Classification Criteria were recruited for the study. Serum nitrite estimation was performed by Griess reaction. Flow-mediated dilation (FMD) assessed using AngioDefender. Inflammatory disease activity measures included disease activity score of 28 joints (DAS28), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Proinflammatory cytokines (TNF-α, IL-6, and IL-1) measured using standard ELISA kits. Twenty-five healthy controls matched for age and sex were included for comparison. The serum nitrite level in patients with RA was markedly elevated as compared with controls ( p  < 0.05). FMD was significantly impaired in RA patients than controls ( p  < 0.05). DAS28 was significantly higher in RA patients ( p  < 0.05). Levels of ESR, CRP, TNF-α, IL-1, and IL-6 were significantly higher in RA patients than controls ( p  < 0.05). Significant positive correlation was observed between nitrite and CRP ( r  = 0.46, p  < 0.05), TNF-α ( r  = 0.53, p  < 0.05), and inverse correlation with FMD ( r =0.62, p  < 0.05). Inflammatory disease activity and endothelial dysfunction in RA are associated with increased concentration of proinflammatory cytokines and NO. Inflammatory triggered release of cytokines induced NO production that mediates endothelial dysfunction. These findings suggest a role for NO in inflammation-induced endothelial dysfunction in RA.
28781105 Adult onset Still's disease occurring during pregnancy: Case-report and literature review. 2018 Feb INTRODUCTION: Adult onset Still's disease is a rare affection classified among non-hereditary autoinflammatory diseases. We here report a case of AOSD revealed during pregnancy with a life-threatening presentation along with a review of 19 cases from literature. CASE: A 38-years old woman was treated in our department for diffuse systemic sclerosis and associated Sjögren syndrome. She was pregnant and presented with acute fever and arthralgias. Laboratory data revealed mild liver cytolysis but a large screening for infectious and auto-immune diseases was negative and hepato-biliar imaging was normal. Ferritin levels were at 41 000 ng/mL with glycosylated ferritin less than 5%. The diagnosis of AOSD was stated and because of persistent fever and polyarthralgias, after exclusion of active infection, steroids were started (prednisone 1 mg/kg) associated with colchicine, which allowed clinical remission and C-reactive protein significant decrease. CONCLUSION: Pregnancy-revealed AOSD appears to be a specifical subset of the disease with a systemic course, flares on first and second trimester, obstetrical complications such as prematurity and IUGR sometimes leading to life-threatening situations requiring parenteral corticotherapy and intravenous immunoglobulins.
28210261 A Comprehensive Gene Expression Meta-analysis Identifies Novel Immune Signatures in Rheuma 2017 Rheumatoid arthritis (RA), a symmetric polyarticular arthritis, has long been feared as one of the most disabling forms of arthritis. Identification of gene signatures associated with RA onset and progression would lead toward development of novel diagnostics and therapeutic interventions. This study was undertaken to identify unique gene signatures of RA patients through large-scale meta-profiling of a diverse collection of gene expression data sets. We carried out a meta-analysis of 8 publicly available RA patients' (107 RA patients and 76 healthy controls) gene expression data sets and further validated a few meta-signatures in RA patients through quantitative real-time PCR (RT-qPCR). We identified a robust meta-profile comprising 33 differentially expressed genes, which were consistently and significantly expressed across all the data sets. Our meta-analysis unearthed upregulation of a few novel gene signatures including PLCG2, HLA-DOB, HLA-F, EIF4E2, and CYFIP2, which were validated in peripheral blood mononuclear cell samples of RA patients. Further, functional and pathway enrichment analysis reveals perturbation of several meta-genes involved in signaling pathways pertaining to inflammation, antigen presentation, hypoxia, and apoptosis during RA. Additionally, PLCG2 (phospholipase Cγ2) popped out as a novel meta-gene involved in most of the pathways relevant to RA including inflammasome activation, platelet aggregation, and activation, thereby suggesting PLCG2 as a potential therapeutic target for controlling excessive inflammation during RA. In conclusion, these findings highlight the utility of meta-analysis approach in identifying novel gene signatures that might provide mechanistic insights into disease onset, progression and possibly lead toward the development of better diagnostic and therapeutic interventions against RA.
28502945 Sporotrichal Tenosynovitis Diagnosed Helpfully by Musculoskeletal Ultrasonography. 2017 A 72-year-old man presented with persistent oligoarthritis and positive results for rheumatoid factor and was suspected of having rheumatoid arthritis (RA). However, the musculoskeletal ultrasonography (MSUS) findings were not consistent with those of typical RA. He had undergone surgery for carpal tunnel syndrome, which allowed both histopathological and microbiological examinations to be performed. A synovial tissue culture was positive for Sporothrix schenckii, and he was diagnosed with sporotrichal tenosynovitis. He received anti-fungal therapy, and the sporotrichal tenosynovitis resolved. This case suggests that MSUS is a useful modality, and sporotrichal tenosynovitis, though rare, should be considered in the differential diagnosis of RA.
28064091 Dose-response characteristics of Clematis triterpenoid saponins and clematichinenoside AR 2017 Mar 20 Clematidis Radix et Rhizoma is a traditional Chinese medicine widely used for treating arthritic disease. Clematis triterpenoid saponins (TS) and clematichinenoside AR (C-AR) have been considered to be responsible for its antiarthritic effects. However, the underling mechanism is still unclear because of their low bioavailability. To address of this issue, metabolomics tools were performed to determine metabolic variations associated with rheumatoid arthritis (RA) and responses to Clematis TS, C-AR and positive drug (Triptolide, TP) treatments. This metabolomics investigation of RA was conducted in collagen-induced arthritis (CIA) rats. Liquid chromatography/mass spectrometry and multivariate statistical tools were used to identify the alteration of serum and urine metabolites associated with RA and responses to drug treatment. As a result, 45 potential metabolites associated with RA were identified. After treatment, a total of 24 biomarkers were regulated to normal like levels. Among these, PC(18:0/20:4), 9,11-octadecadienoic acid, arachidonic acid, 1-methyladenosine, valine, hippuric acid and pantothenic acid etc, were reversed in Clematis TS and C-AR groups. Tetrahydrocortisol was regulated to normal levels in Clematis TS and TP groups, while 3,7,12-trihydroxycholan-24-oic acid was regulated in C-AR and TP groups. Biomarkers like citric acid, p-cresol glucuronide, creatinine, cortolone were reversed in TP group.
28555437 Autoimmunity in 2016. 2017 Aug The number of peer-reviewed articles published during the 2016 solar year and retrieved using the "autoimmunity" key word remained stable while gaining a minimal edge among the immunology articles. Nonetheless, the quality of the publications has been rising significantly and, importantly, acquisitions have become available through scientific journals dedicated to immunology or autoimmunity. Major discoveries have been made in the fields of systemic lupus erythematosus, rheumatoid arthritis, autoimmunity of the central nervous system, vasculitis, and seronegative spondyloarthrithritides. Selected examples include the role of IL17-related genes and long noncoding RNAs in systemic lupus erythematosus or the effects of anti-pentraxin 3 (PTX3) in the treatment of this paradigmatic autoimmune condition. In the case of rheumatoid arthritis, there have been reports of the role of induced regulatory T cells (iTregs) or fibrocytes and T cell interactions with exciting implications. The large number of studies dealing with neuroimmunology pointed to Th17 cells, CD56(bright) NK cells, and low-level TLR2 ligands as involved in multiple sclerosis, along with a high salt intake or the micriobiome-derived Lipid 654. Lastly, we focused on the rare vasculitides to which numerous studies were devoted and suggested that unsuspected cell populations, including monocytes, mucosal-associated invariant T cells, and innate lymphoid cells, may be crucial to ANCA-associated manifestations. This brief and arbitrary discussion of the findings published in 2016 is representative of a promising background for developments that will enormously impact the work of laboratory scientists and physicians at an exponential rate.
28975544 The role of α9β1 integrin and its ligands in the development of autoimmune diseases. 2018 Mar Adhesion of cells to extracellular matrix proteins through integrins expressed on the cell surface is important for cell adhesion/motility, survival, and differentiation. Recently, α9β1 integrin was reported to be important for the development of autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and their murine models. In addition, ligands for α9β1 integrin, such as osteopontin and tenascin-C, are well established as key regulators of autoimmune diseases. Therefore, this review focused on the role of interactions between α9β1 integrin and its ligands in the development of autoimmune diseases.
28763759 Metabolomics analysis of Danggui Sini decoction on treatment of collagen-induced arthritis 2017 Sep 1 Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by persistent joint inflammation leading to bone and cartilage damage and even disability. However, the pathogenesis of RA is multi-factorial and to a large degree, remains unknown. Danggui Sini decoction (DSD), a traditional Chinese medicine (TCM) formula, has been widely used as a remedy for rheumatoid arthritis (RA) in recent years. In our study, (1)H-nuclear magnetic resonance ((1)H NMR) based metabolomics analysis of 7 potential biomarkers, including taurine (1), urea (2), betaine (3), pyruvate (4), hippurate (5), succinate (6) and acetone (7) was performed to investigate the progression of RA and assess the efficacy of DSD in collagen-induced arthritis (CIA) rats. According to pathway analysis using identified metabolites and correlation construction, taurine and hypotaurine metabolism, gut microbiota metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, the citrate cycle (TCA cycle) and lipid metabolism were recognized as being the most influenced metabolic pathways associated with RA. As a result, deviations of metabolites 1, 3, 4, 5, 6 and 7 in CIA rats were improved by DSD, which suggested that DSD mediated the abnormal metabolic pathways synergistically. In summary, the efficacy and its underlying therapeutic mechanisms of DSD on RA were systematically investigated and expect to provide a new insight in relevant studies of other TCM formulas.
30229229 Total Ankle Arthroplasty for Rheumatoid Arthritis in Japanese Patients: A Retrospective St 2017 Dec 28 BACKGROUND: Outcomes after total ankle arthroplasty (TAA) combined with additive techniques (augmentation of bone strength, control of soft-tissue balance, adjustment of the loading axis) for the treatment of rheumatoid arthritis were evaluated after intermediate to long-term follow-up. The influences of biologic treatment on the outcomes after TAA were also evaluated. METHODS: We performed a retrospective observational study involving 50 ankles (44 patients) that underwent TAA for the treatment of rheumatoid arthritis. The mean duration of follow-up was 7.1 years. Clinical outcomes were evaluated with use of the Japanese Society for Surgery of the Foot (JSSF) scale score and a postoperative self-administered foot-evaluation questionnaire (SAFE-Q). Radiographic findings were evaluated as well. These parameters also were compared between patients managed with and without biologic treatment. RESULTS: This procedure significantly improved the clinical scores of the JSSF rheumatoid arthritis foot and ankle scale (p < 0.0001). Forty-eight of the 50 ankles had no revision TAA surgery. Subsidence of the talar component was seen in 8 ankles (6 in the biologic treatment group and 2 in the non-biologic treatment group); 2 of these ankles (both in the biologic treatment group) underwent revision TAA. The social functioning score of the SAFE-Q scale at the time of the latest follow-up was significantly higher in the biologic treatment group (p = 0.0079). The dosage of prednisolone (p = 0.0003), rate of usage of prednisolone (p = 0.0001), and disease-activity score (p < 0.01) at the time of the latest follow-up were all significantly lower in the biologic treatment group. CONCLUSIONS: TAA is recommended for the treatment of rheumatoid arthritis if disease control, augmentation of bone strength, control of soft-tissue balance, and adjustment of the loading axis are taken into account. The prevention of talar component subsidence remains a challenge in patients with the combination of subtalar fusion, rheumatoid arthritis, and higher social activity levels. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
30881239 Successful Interprofessional Treatment of Juvenile Rheumatoid Arthritis: A Case Report. 2017 Apr A 9-y-old boy with severe juvenile rheumatoid arthritis who had been recommended for bilateral hip replacement received treatment for more than 8 y from an interprofessional group of clinicians. The clinicians provided chiropractic, naturopathic, and acupuncture care, in addition to pediatrics, rheumatology, orthopedics, and physical therapy care. This process was not easy; the patient used crutches for 2 y during treatment and experienced severe pain secondary to multiple joint pathology. He is now aged 17 y, and he regularly plays golf and basketball with his own hips.
30375526 Development of Atherosclerotic Cardiovascular Mortality in Gouty Arthritis and Rheumatoid 2017 Mar OBJECTIVES: This study aims to evaluate the mean platelet volume (MPV) and neutrophil-lymphocyte ratio (NLR) in gouty arthritis (GA) and rheumatoid arthritis (RA) patients, as well as their relationship with atherosclerotic cardiovascular mortality (ACVM). PATIENTS AND METHODS: The study included 122 GA patients (96 males, 26 females; mean age 64.6±13.4 years; range 34 to 82 years), 82 RA patients (40 males, 42 females; mean age 62.1±12.1 years; range 29 to 83 years), and 61 healthy controls (34 males, 27 females; mean age 65.3±4.8 years; range 33 to 80 years). Clinical and ACVM data were obtained from medical charts. Erythrocyte sedimentation rate, C-reactive protein, MPV, and NLR were recorded at the time of diagnosis and one month after therapy. RESULTS: Mean platelet volume in GA (8.49±1.5) and RA (7.98±0.99) groups were significantly lower than in healthy controls (9.8±15) (p<0.001). NLR in healthy controls (1.9±0.74) was significantly lower than in GA (3.6±2.3) and RA (3.7±2.5) groups (p<0.001). After treatment, MPV did not change significantly in GA and RA groups (p values >0.05); however, NLR decreased in both groups (p<0.001). Nine GA and 12 RA patients died from ACVM during follow-up. GA patients with ACVM were older and had more frequent hypertension, higher MPV, and higher intercritical CRP level. In multivariate analysis, MPV was an independent poor prognostic factor for ACVM in GA patients. CONCLUSION: Gouty arthritis and RA patients had significantly lower MPV and significantly higher NLR than controls. MPV might be used as a potential biomarker for the development of ACVM in GA.
28598360 Role of Gut Microbiota in Rheumatoid Arthritis. 2017 Jun 9 Rheumatoid arthritis (RA) is a systemic autoimmune disease, caused by both genetic and environmental factors. Recently, investigators have focused on the gut microbiota, which is thought to be an environmental agent affecting the development of RA. Here we review the evidence from animal and human studies that supports the role of the gut microbiota in RA. We and others have demonstrated that the abundance of Prevotella copri is increased in some early RA. We have also used gnotobiotic experiments to show that dysbiosis in RA patients contributed to the development of Th17 cell-dependent arthritis in intestinal microbiota-humanized SKG mice. On the other hand, Prevotella histicola from human gut microbiota suppressed the development of arthritis. In summary, Prevotella species are involved in the pathogenesis of arthritis.
28270202 Rheumatology in Africa-challenges and opportunities. 2017 Mar 7 Africa faces many health challenges despite sustained growth and development over the past decade. Contributory factors are the lack of financial resources, an inadequate health professional workforce, a high burden of communicable diseases, and an increasing burden of non-communicable diseases. Rheumatology services are limited or non-existent in many parts of sub-Saharan Africa. Over the past decade, partnerships with international academic institutions have resulted in some progress in the training of rheumatologists and health professionals and development of rheumatology services in countries such as Kenya, Nigeria, and Zambia. Basic diagnostic tests, biological agents, and arthroplasty are either unavailable or not affordable by the majority of the population. Urbanization has resulted in a change in the epidemiology of rheumatic diseases with an increase in the prevalence of gout, rheumatoid arthritis, systemic lupus erythematosus, and scleroderma over the past four decades. Future growth of rheumatology services will depend on identifying committed individuals in underserved countries for training and supporting them to educate medical students, physicians, and health professionals in their home countries. There is a need to develop models of care using all categories of health workers and identify prevention strategies and cost-effective management programs for low resource settings. Africa affords an opportunity for collaborative research, including genetic and epigenetic studies, to improve our understanding of many of the rheumatic diseases.
29383169 P53-derived hybrid peptides induce apoptosis of synovial fibroblasts in the rheumatoid joi 2017 Dec 29 Loss of p53-mediated suppression by its dominant-negative counterpart is commonly observed in human cancers, and activating p73 is a therapeutic strategy in p53-mutated oncological patients. In synovial fibroblasts (SFs) from rheumatoid arthritis (RA), mutant p53 can lead to the transformation-like features with resistance to the apoptosis induction. We examined whether intra-articular (i.a.) administration of p53-derived hybrid peptides to activate p73 can induce apoptosis of SFs by using adenoviral vectors encoding 37 amino acid (Ad37AA), a p53-derived hybrid peptide capable of activating p73, to transduce SFs in vitro and inject collagen-induced arthritis (CIA) joints in vivo. Increased p73 expression was found in synovial lining layers and SFs of RA patients and CIA rats. Higher expression of p53 up-regulated modulator of apoptosis (PUMA) and Bax with enhanced apoptosis were found in Ad37AA-transduced SFs, and silencing p73 abrogated the up-regulation of PUMA and Bax. Articular indexes and histologic scores were reduced in Ad37AA-injected joints with decreased SF densities, increased apoptotic cell numbers, and higher PUMA expression levels. We demonstrate that i.a. administration of p53-derived hybrid peptides can activate p73 to induce apoptosis of SFs and ameliorate the rheumatoid joint, implicating an enhancement of the p73-dependent apoptotic mechanism as a pharmacological strategy in the RA therapy.
28484458 Use of Lentiviral Particles As a Cell Membrane-Based mFasL Delivery System for In Vivo Tre 2017 During budding, lentiviral particles (LVP) incorporate cell membrane proteins in the viral envelope. We explored the possibility of harnessing this process to generate LVP-expressing membrane proteins of therapeutic interest and studied the potential of these tools to treat different pathologies. Fas-mediated apoptosis is central to the maintenance of T cell homeostasis and prevention of autoimmune processes. We prepared LVP that express murine FasL on their surface. Our data indicate that mFasL-bearing LVP induce caspase 3 and 9 processing, cytochrome C release, and significantly more cell death than control LVP in vitro. This cytotoxicity is blocked by the caspase inhibitor Z-VAD. Analysis of the application of these reagents for the treatment of inflammatory arthritis in vivo suggests that FasL-expressing LVP could be useful for therapy in autoimmune diseases such as rheumatoid arthritis, where there is an excess of Fas-expressing activated T cells in the joint. LVP could be a vehicle not only for mFasL but also for other membrane-bound proteins that maintain their native conformation and might mediate biological activities.
28161984 Formulation of piperine solid lipid nanoparticles (SLN) for treatment of rheumatoid arthri 2017 Jun The purpose of this work was to formulate piperine solid lipid nanoparticle (SLN) dispersion to exploit its efficacy orally and topically. Piperine SLN were prepared by melt emulsification method and formula was optimized by the application of 3(2) factorial design. The nanoparticulate dispersion was evaluated for particle size, entrapment efficiency and zeta potential (ZP). Optimized batch (128.80 nm average size, 78.71% entrapment efficiency and -23.34 mV zeta potential) was characterized for differential scanning calorimetry (DSC), X-ray diffraction which revealed amorphous nature of piperine in SLN. The prepared SLN were administered orally and topically to CFA-induced arthritic rats. Ex vivo study using Franz diffusion cell indicate that piperine from SLN gel formulation accumulates in the skin. Pharmacodynamic study result indicates both the topical and oral piperine evoked a significant response compared to orally administered chloroquine suspension. The results of ELISA show significant reduction in TNFα in treated rat which might be the reason behind the DMARD action of piperine SLN.
28620302 Adoption of Biosimilar Infliximab for Rheumatoid Arthritis, Ankylosing Spondylitis, and In 2017 Introduction: Introducing biosimilar infliximab for the treatment in rheumatology (rheumatoid arthritis and ankylosing spondylitis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis) may reduce treatment costs associated with biologics. This study aimed to investigate the budget impact of adopting biosimilar infliximab in five European countries, considering that the budget impact includes the adoption of biosimilar infliximab and the availability of biologic alternatives such as vedolizumab, biosimilar etanercept, biosimilar rituximab, and other relevant factors. Methods: An existing budget impact model was adapted to forecast the budget impact in the UK, Germany, France, Spain, and Italy. Epidemiological parameters were derived from published literature reviewed in July 2015. Current market shares of biologics were derived from Therapy Watch (2012/2013 data). Respondents in a Delphi panel, conducted in 2015 and consisting of several leading rheumatologists and gastroenterologists from different nationalities, were asked to forecast uptake of biosimilar infliximab and estimate the proportion of patients eligible for a particular type of biological treatment, including biosimilar infliximab. Scenario analyses assessed the influence of various factors, including price reductions, on the budget. Results: Uptake of biosimilar infliximab was particularly expected for naïve patients; switching patients that already received other biologics was not expected much. Market shares after 5 years of biosimilar infliximab were ~2% in rheumatology in all five countries and in gastroenterology ranged from 4% in France to over 30% in Italy. Except for France, budgets were expected to decrease for rheumatologic diseases. For gastroenterology, budgets were expected to decrease in Spain and Italy. Budgets were expected to increase substantially in the UK and Germany, due to the introduction of vedolizumab in the studied period. In France, budget was expected to slightly increase for ankylosing spondylitis, Crohn's Disease, and ulcerative collitis. Savings in budget were expected in all countries, for all diseases, when larger price discounts on biosimilar infliximab were used. Discussion and Conclusion: This study has shown that only when price reductions are large enough (i.e., 50% or more), physicians indicated that they will prescribe biosimilars. Policy makers should ensure substantial price reductions and stimulate physicians to use biosimilar products, to obtain savings in healthcare budgets.
28824652 Tumor Necrosis Factor (TNF) Bioactivity at the Site of an Acute Cell-Mediated Immune Respo 2017 The impact of anti-tumor necrosis factor (TNF) therapies on inducible TNF-dependent activity in humans has never been evaluated in vivo. We aimed to test the hypothesis that patients responding to anti-TNF treatments exhibit attenuated TNF-dependent immune responses at the site of an immune challenge. We developed and validated four context-specific TNF-inducible transcriptional signatures to quantify TNF bioactivity in transcriptomic data. In anti-TNF treated rheumatoid arthritis (RA) patients, we measured the expression of these biosignatures in blood, and in skin biopsies from the site of tuberculin skin tests (TSTs) as a human experimental model of multivariate cell-mediated immune responses. In blood, anti-TNF therapies attenuated TNF bioactivity following ex vivo stimulation. However, at the site of the TST, TNF-inducible gene expression and genome-wide transcriptional changes associated with cell-mediated immune responses were comparable to that of RA patients receiving methotrexate only. These data demonstrate that anti-TNF agents in RA patients do not inhibit inducible TNF activity at the site of an acute inflammatory challenge in vivo, as modeled by the TST. We hypothesize instead that their therapeutic effects are limited to regulating TNF activity in chronic inflammation or by alternative non-canonical pathways.