Rheumatology-Rhumatologie
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Scooped by Gilbert C FAURE
May 22, 2017 1:54 PM
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Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study

Effect of secukinumab on clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III MEASURE 1 study | Rheumatology-Rhumatologie | Scoop.it
Objective To evaluate the effect of secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic changes through 2 years in patients with ankylosing spondylitis (AS).

Methods In the phase III MEASURE 1 study, patients were randomised to receive intravenous secukinumab 10 mg/kg (at baseline, week 2 and week 4) followed by subcutaneous secukinumab 150 mg (intravenous 150 mg; n=125) or 75 mg (intravenous 75 mg; n=124) every four weeks, or matched placebo (n=122). Placebo-treated patients were re-randomised to subcutaneous secukinumab 150 or 75 mg from week 16. Clinical efficacy assessments included Assessment of SpondyloArthritis international Society 20 (ASAS20) response rates through week 104. Radiographic changes at week 104 were assessed using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS).

Results 97 (77.6%) and 103 (83.1%) patients in the intravenous 150 mg and intravenous 75 mg groups, respectively, completed week 104. In the full analysis set (intent-to-treat), ASAS20 response rates at week 104 were 73.7% and 68.0% in the intravenous 150 mg and intravenous 75 mg groups, respectively. Among patients with evaluable X-rays who were originally randomised to secukinumab (n=168), mean change in mSASSS from baseline to week 104 was 0.30±2.53. Serious adverse events were reported in 12.2% and 13.4% of patients in the 150 mg and 75 mg groups, respectively.

Conclusions Secukinumab improved AS signs and symptoms through 2 years of therapy, with no unexpected safety findings. Data from this study suggest a low mean progression of spinal radiographic changes, which will need to be confirmed in longer-term controlled studies.

Trial registration number NCT01358175.
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Scooped by Gilbert C FAURE
April 13, 2017 2:12 AM
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Moxibustion versus diclofenac sodium gel for the treatment of knee osteoarthritis: a study protocol for a double-blinded, double-placebo, randomised controlled trial

Introduction Knee osteoarthritis is a common form of arthritis in elderly patients that is characterised by pain and functional limitation. Moxibustion has been employed to relieve chronic pain as an alternative therapy for knee osteoarthritis. However, the evidence of its efficacy is equivocal due to the low methodological quality in most clinical studies. Therefore, we are performing a double-blinded, double-placebo, randomised controlled trial to evaluate the efficacy of moxibustion in participants with knee osteoarthritis.

Methods and analysis This is a multicentre, double-blinded, double-placebo, randomised controlled clinical trial. 144 eligible participants with knee osteoarthritis will be randomly assigned to two different groups in a 1:1 ratio. Participants in the moxibustion group will undergo active moxibustion plus placebo gel, whereas participants in the control group will receive diclofenac sodium gel plus placebo moxibustion. Each participant will receive 12 sessions of active/placebo moxibustion at three acupoints (ST35, ST36 and EX-LE4) as well as 2 months of follow-up. Diclofenac sodium gel or placebo gel at a dose of 4 g per knee will be applied three times per day for 4 weeks. The primary outcome measure will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score change at the end of the intervention period from baseline. The secondary outcome measures include changes of other subscales (pain, stiffness and function) of WOMAC, visual analogue scale and patient globalassessment. The safety of moxibustion and diclofenac sodium gel will be assessed at every visit.

Ethics and dissemination This trial has been approved by the Sichuan Regional Ethics Review Committee (permission number: 2015KL-014). The results of this study are expected to provide clinical evidence on the efficacy of moxibustion for pain relief and physical function improvement in patients with knee osteoarthritis. The findings will be submitted for publication in peer-reviewed medical journals and presented at relevant academic conferences.

Trial registration number NCT02769572.
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Scooped by Gilbert C FAURE
February 14, 2017 12:43 PM
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Higher efficacy of anti-IL-6/IL-21 combination therapy compared to monotherapy in the induction phase of Th17-driven experimental arthritis

Higher efficacy of anti-IL-6/IL-21 combination therapy compared to monotherapy in the induction phase of Th17-driven experimental arthritis | Rheumatology-Rhumatologie | Scoop.it
Th17 cells and their cytokines are linked to the pathogenesis of rheumatoid arthritis, a chronic autoimmune disease characterized by joint inflammation. Th17 development is initiated by combined signaling of TGF-β and IL-6 or IL-21, and can be reduced in the absence of either IL-6 or IL-21. The aim of this study was to assess whether combinatorial IL-6/IL-21 blockade would more potently inhibit Th17 development, and be more efficacious in treating arthritis than targeting either cytokine. We assessed in vitro Th17 differentiation efficacy in the absence of IL-6 and/or IL-21. To investigate in vivo effects of IL-6/IL-21 blockade on Th17 and arthritis development, antigen-induced arthritis (AIA) was induced in IL-6-/- x IL-21R-/- mice. The therapeutic potential of this combined blocking strategy was assessed by treating mice with collagen-induced arthritis (CIA) with anti-IL-6R antibodies and soluble (s)IL-21R.Fc. We demonstrated that combined IL-6/IL-21 blocking synergistically reduced in vitro Th17 differentiation. In mice with AIA, absence of IL-6 and IL-21 signaling more strongly reduced Th17 levels and resulted in stronger suppression of arthritis than the absence of either cytokine. Additionally, anti-IL-6/anti-IL-21 treatment of CIA mice during the arthritis induction phase reduced disease development more potent than IL-6 or IL-21 inhibition alone, as effective as anti-TNF treatment. Collectively, these results suggest dual IL-6/IL-21 inhibition may be a more efficacious therapeutic strategy compared to single cytokine blockade to suppress arthritis development.
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Scooped by Gilbert C FAURE
February 6, 2017 1:06 PM
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Statins May Protect Against RA - The Rheumatologist

Statins May Protect Against RA - The Rheumatologist | Rheumatology-Rhumatologie | Scoop.it
A recent observational study found a link between high-intensity statin therapy and a 23% reduced risk of rheumatoid arthritis. Although further research is needed, researchers note this study “provides robust evidence of a protective effect of high-intensity statins on the risk of RA.”
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Scooped by Gilbert C FAURE
December 24, 2016 6:47 AM
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Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis

Increase in circulating Th17 cells during anti-TNF therapy is associated with ultrasonographic improvement of synovitis in rheumatoid arthritis | Rheumatology-Rhumatologie | Scoop.it
Anti-TNF agents have revolutionised rheumatoid arthritis (RA) treatment; however, a third of patients fail to achieve therapeutic responses. Unexpectedly, studies in murine and human arthritis have indicated that anti-TNF treatment can increase circulating T helper 17 (Th17) cells, but the relationship to treatment response is unclear. To identify immune correlates of anti-TNF treatment response, we conducted a longitudinal study using clinical, ultrasound and T cell assessments. Patients with RA (n = 25) were studied at protocol visits during the initial 12 weeks of anti-TNF treatment. Improvement in the disease activity score of 28 joints (DAS28) >1.2 defined treatment responders (n = 16) and non-responders (n = 9). Changes in synovial thickening and vascularity of 10 metacarpophalangeal joints were quantitatively assessed by grey scale and power Doppler ultrasound. The frequency of circulating Th17 cells was determined by IL17 enzyme-linked immunospot assay (Elispot) and flow cytometry (fluorescence-activated cell sorting (FACS)). The frequency of circulating IL17-producing cells increased significantly 12 weeks after anti-TNF initiation (Elispot median (range) specific spot forming cells (spSFC)/106 360 (280–645) vs 632 (367 − 1167), p = 0.003). The increase in CD4 + IL17+ cells at 12 weeks was confirmed by FACS (median (range) %, 0.7 (0.5–0.9) vs 1.05 (0.6–1.3); p = 0.01). The increase in circulating Th17 cells inversely correlated with reduction in synovial vascularity (r = -0.68, p = 0.007) and thickening (r = -0.39; p = 0.04). Higher frequencies of circulating Th17 cells at baseline were associated with poorer anti-TNF treatment response defined by ultrasonographic measures. These results demonstrate a link between changes in circulating Th17 cells with resolution of ultrasonographic features of synovial inflammation and vascularity during anti-TNF treatment. The findings may reflect redistribution of Th17 cells from inflamed joints or TNF-driven regulation of Th17 cell production. ClinicalTrials.gov:
NCT01060098

. Registered 29 January 2010.
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Scooped by Gilbert C FAURE
September 9, 2016 3:09 AM
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Interpretation of the evidence for the efficacy and safety of statin therapy

Interpretation of the evidence for the efficacy and safety of statin therapy | Rheumatology-Rhumatologie | Scoop.it
This Review is intended to help clinicians, patients, and the public make informed
decisions about statin therapy for the prevention of heart attacks and strokes. It
explains how the evidence that is available from randomised controlled trials yields
reliable information about both the efficacy and safety of statin therapy. In addition,
it discusses how claims that statins commonly cause adverse effects reflect a failure
to recognise the limitations of other sources of evidence about the effects of treatment.
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Suggested by Société Francaise d'Immunologie
August 5, 2016 9:53 AM
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Possible psoriasis drug target identified

Possible psoriasis drug target identified | Rheumatology-Rhumatologie | Scoop.it
Researchers have discovered a protein involved in psoriasis, a highly common skin disease, opening up new potentials for therapy.
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Scooped by Gilbert C FAURE
May 20, 2016 3:21 PM
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Novel Oral Therapies for Psoriasis and Psoriatic Arthritis

Abstract
Several classes of new oral therapy are in use or in development for the treatment of psoriasis.
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Scooped by Gilbert C FAURE
April 21, 2016 5:15 AM
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Influenza and Pneumococcal Vaccination Uptake in Patients with Rheumatoid Arthritis Treated with Immunosuppressive Therapy in the UK: A Retrospective Cohort Study Using Data from the Clinical Pract...

Influenza and Pneumococcal Vaccination Uptake in Patients with Rheumatoid Arthritis Treated with Immunosuppressive Therapy in the UK: A Retrospective Cohort Study Using Data from the Clinical Pract... | Rheumatology-Rhumatologie | Scoop.it
Introduction Guidelines for the management of rheumatoid arthritis (RA) recommend using influenza and pneumococcal vaccinations to mitigate infection risk. The level of adherence to these guidelines is not well known in the UK.
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Scooped by Gilbert C FAURE
February 11, 2016 4:43 AM
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B-cell-targeted therapy in systemic vasculitis : Current Opinion in Rheumatology

B-cell-targeted therapy in systemic vasculitis : Current Opinion in Rheumatology | Rheumatology-Rhumatologie | Scoop.it

Purpose of review: The present review discusses the evidence supporting the use of B-cell-targeted t

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Scooped by Gilbert C FAURE
January 21, 2016 4:01 AM
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Arthritis Research & Therapy | Full text | B-cell and T-cell quantification in minor salivary glands in primary Sjögren’s syndrome: development and validation of a pixel-based digital procedure

Evaluating lymphocytic infiltration of minor salivary gland biopsy in primary Sjögren’s syndrome is challenging. We developed and evaluated a digital method for quantifying B and T lymphocytes in whole minor salivary gland biopsy slides.

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Scooped by Gilbert C FAURE
January 18, 2016 1:12 PM
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Arthritis Research & Therapy | Full text | A longitudinal genome-wide association study of anti-tumor necrosis factor response among Japanese patients with rheumatoid arthritis

Studies of Caucasian patients with rheumatoid arthritis (RA) to identify genetic biomarkers of anti-tumor necrosis factor (TNF) response have used response at a single time point as the phenotype with which single nucleotide polymorphism (SNP)...

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Scooped by Gilbert C FAURE
January 15, 2016 10:53 AM
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Effective osteoarthritis therapy with nucleic acid medicine - Technology Org

Effective osteoarthritis therapy with nucleic acid medicine - Technology Org | Rheumatology-Rhumatologie | Scoop.it

Researchers at the University of Tokyo have demonstrated that in-joint delivery of a transcription factor messenger RNA (mRNA)

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Scooped by Gilbert C FAURE
April 28, 2017 1:21 PM
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Risk and severity of herpes zoster in patients with rheumatoid arthritis receiving different immunosuppressive medications: a case–control study in Asia

Objective Increasing evidence indicates that the risk of herpes zoster (HZ) is elevated in rheumatoid arthritis (RA). Little is known about the epidemiology of HZ in patients with RA in Asia. The aim of this study was to determine the risk factors and outcomes of HZ among patients with RA.

Design A case–control study.

Setting A medical centre in Asia.

Participants A total of 9025 newly diagnosed and eligible patients with RA (International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 714.0) during the period 2001–2014. Among them, 275 (3.05%) were newly diagnosed with HZ (ICD-9-CM code 053.0) after the RA identification. As the control group, patients with RA without HZ were matched for age, gender and RA disease duration at the time of HZ infection with the RA-HZ case group at a ratio of 4:1, and a total of 1100 control subjects were selected.

Outcome measures We estimated ORs using conditional logistic regression to investigate the risk and severity of HZ among patients with RA receiving different immunosuppressive medications.

Results Exposure to corticosteroids (≥10 mg/day adjusted OR (aOR)=2.30, 95% CI 1.25 to 4.22, p=0.01), anti-tumour necrosis factor biologicals (aOR=2.07, 95% CI 1.34 to 3.19, p=0.001) and conventional synthetic disease-modifying anti-rheumatic drugs (methotrexate (aOR=1.98, 95% CI 1.43 to 2.76, p<0.001) and hydroxychloroquine (aOR=1.95, 95% CI 1.39 to 2.73, p<0.001)) was associated with an increased HZ risk in patients with RA. The association between the use of corticosteroids and HZ risk was dose-dependent (ptrend<0.001). Time-to-HZ diagnosis among patients with RA receiving biological medications was significantly shorter than that in patients not receiving biological medications. A higher proportion of severe HZ and ophthalmic involvement was found in patients with RA receiving biologicals.

Conclusions There was an increased risk of HZ in patients with RA taking specific immunosuppressive medication. Biologicals used were associated with severe HZ occurrence. Therefore, it is important to closely monitor and prevent severe HZ complications during specific immunosuppressive therapy.
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Rescooped by Gilbert C FAURE from Osteoporosis New drugs Review
March 3, 2017 6:37 AM
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Denosumab for the treatment of osteoporosis

Denosumab for the treatment of osteoporosis | Rheumatology-Rhumatologie | Scoop.it
Abstract Denosumab, a specific inhibitor of RANK ligand, is a novel therapy for postmenopausal osteoporosis and related disorders. An extensive clinical development program has evaluated the clinical efficacy and safety of denosumab with several thousand patients being followed for up to 10 years. Combined with more than six years of postmarketing experience, these studies provide substantial confidence that denosumab is a convenient and appropriate treatment for patients, including Asians, at high risk for fracture. This review will summarize the clinical development of denosumab and lessons learned since its approval for clinical use in 2010. Keywords Denosumab; RANK ligand; Osteoporosis; Fracture; Drug safety

Via Krishan Maggon
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Scooped by Gilbert C FAURE
February 6, 2017 1:14 PM
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Efficacy and Survival of Systemic Psoriasis Treatments: An Analysis of the Swiss Registry SDNTT

Background: The Swiss psoriasis registry SDNTT (Swiss Dermatology Network for Targeted Therapies) records the long-term safety and effectiveness of systemic treatment regimens for psoriasis. Patients and Methods: Patients with moderate to severe psoriasis are included in the SDNTT when treatment with a conventional systemic agent or biologic is initiated that was not previously used by the respective patient. Patients are followed over a 5-year period. Clinical data are obtained every 3-6 months using standardized case report forms. Here, baseline data and follow-up data for 1 year of patients included from October 2011 until December 2014 were analyzed. Results: Within 39 months, 323 patients from 7 tertiary dermatology centers in Switzerland were recruited in the SDNTT; 165 patients received biologics and 158 conventional systemic therapies. Patients treated with biologics had a significantly higher severity (PASI 11.3 vs. 9.2, BSA 15.6 vs.11.9, psoriatic arthritis 36.4 vs. 10.8%; p ≤ 0.005, p ≤ 0.013, p ≤ 0.001) and a longer duration of illness (19.2 vs. 14.4 years, p ≤ 0.003) compared to patients starting a conventional systemic treatment. PASI reduction was satisfying in both treatment groups, with 60.6% of patients treated with biologics achieving PASI75 after 1 year compared to 54.2% of patients receiving conventional systemic drugs (nonsignificant). On average, the drug survival in patients receiving a biologic therapy was significantly longer than those receiving conventional systemic treatments (30.5 vs. 19.2 months, p ≤ 0.001). Conclusions: In the real-world setting of a prospective national therapy registry, the application of current therapeutic guidelines for patients with moderate to severe psoriasis resulted in a PASI reduction of approximately 70% within the first year of treatment, but current therapeutic targets of PASI75 and PASI90 were reached in only 58 and 36% of patients, respectively, at 1 year, highlighting a gap in efficacy between selective clinical trials and the real-world setting.
Dermatology
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Scooped by Gilbert C FAURE
January 12, 2017 9:24 AM
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TCR repertoire sequencing identifies synovial Treg cell clonotypes in the bloodstream during active inflammation in human arthritis

Objectives
The imbalance between effector and regulatory T (Treg) cells is crucial in the pathogenesis of autoimmune arthritis. Immune responses are often investigated in the blood because of its accessibility, but circulating lymphocytes are not representative of those found in inflamed tissues. This disconnect hinders our understanding of the mechanisms underlying disease. Our goal was to identify Treg cells implicated in autoimmunity at the inflamed joints, and also readily detectable in the blood upon recirculation.
Methods
We compared Treg cells of patients with juvenile idiopathic arthritis responding or not to therapy by using: (i) T cell receptor (TCR) sequencing, to identify clonotypes shared between blood and synovial fluid; (ii) FOXP3 Treg cell-specific demethylated region DNA methylation assays, to investigate their stability and (iii) flow cytometry and suppression assays to probe their tolerogenic functions.
Results
We found a subset of synovial Treg cells that recirculated into the bloodstream of patients with juvenile idiopathic and adult rheumatoid arthritis. These inflammation-associated (ia)Treg cells, but not other blood Treg cells, expanded during active disease and proliferated in response to their cognate antigens. Despite the typical inflammatory-skewed balance of immune mechanisms in arthritis, iaTreg cells were stably committed to the regulatory lineage and fully suppressive. A fraction of iaTreg clonotypes were in common with pathogenic effector T cells.
Conclusions
Using an innovative antigen-agnostic approach, we uncovered a population of bona fide synovial Treg cells readily accessible from the blood and selectively expanding during active disease, paving the way to non-invasive diagnostics and better understanding of the pathogenesis of autoimmunity.
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Scooped by Gilbert C FAURE
December 4, 2016 11:16 AM
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A doctor with a bad knee runs into one-size-fits-all medicine

A doctor with a bad knee runs into one-size-fits-all medicine | Rheumatology-Rhumatologie | Scoop.it
His post-surgery physical therapy was standard, but his problem was not.
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Scooped by Gilbert C FAURE
August 21, 2016 7:51 AM
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Room for more IL-6 blockade? Sarilumab for the treatment of rheumatoid arthritis

Room for more IL-6 blockade? Sarilumab for the treatment of rheumatoid arthritis | Rheumatology-Rhumatologie | Scoop.it
(2016). Room for more IL-6 blockade? Sarilumab for the treatment of rheumatoid arthritis. Expert Opinion on Biological Therapy. Ahead of Print. doi: 10.1080/14712598.2016.1217988
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Scooped by Gilbert C FAURE
July 19, 2016 3:58 AM
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Cartilage grown in a lab 'could cut the need for artificial hips'

Cartilage grown in a lab 'could cut the need for artificial hips' | Rheumatology-Rhumatologie | Scoop.it
Scientists have programmed stem cells to grow new arthritis-fighting cartilage on a scaffold shaped like the ball of a hip joint. Gene therapy was used t
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Scooped by Gilbert C FAURE
May 16, 2016 1:39 PM
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Stem Cell Research & Therapy

Stem Cell Research & Therapy | Rheumatology-Rhumatologie | Scoop.it

Stem Cell Research & Therapy is the major forum for translational research into stem cell therapies.

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Scooped by Gilbert C FAURE
February 15, 2016 10:05 AM
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Intensification to triple therapy non-biologic disease-modifying antirheumatic drugs for rheumatoid arthritis in the United States from 2009 to 2014 - Sparks - Arthritis & Rheumatology - Wiley Onli...

Intensification to triple therapy non-biologic disease-modifying antirheumatic drugs for rheumatoid arthritis in the United States from 2009 to 2014 - Sparks - Arthritis & Rheumatology - Wiley Onli... | Rheumatology-Rhumatologie | Scoop.it

Objective. Several trials suggest that triple therapy (methotrexate, sulfasalazine, and hydroxychloroquine) and biologic disease-modifying antirheumatic drugs (bDMARD) have similar efficacy in rheumatoid arthritis (RA).

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Scooped by Gilbert C FAURE
January 23, 2016 4:07 AM
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Arthritis Research & Therapy | Full text | Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation but has no effect on bone formation in the delayed-type hypersensitivity a...

The aims of the present study were to determine the relationship between bone destruction and bone formation in the delayed-type hypersensitivity arthritis (DTHA) model and to evaluate the effect of receptor activator of nuclear factor κB...

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Scooped by Gilbert C FAURE
January 19, 2016 5:33 AM
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Arthritis Research & Therapy | Full text | DKK1 expression by synovial fibroblasts in very early rheumatoid arthritis associates with lymphocyte adhesion in an in vitro flow co-culture system

Synovial fibroblasts play a key role in joint destruction and regulation of the inflammatory infiltrate in established rheumatoid arthritis (RA). The mechanisms by which this occurs in the earliest stages of RA are largely unknown.

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Scooped by Gilbert C FAURE
January 15, 2016 10:54 AM
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Arthritis Research & Therapy | Full text | Overexpression of TLR2 and TLR9 on monocyte subsets of active rheumatoid arthritis patients contributes to enhance responsiveness to TLR agonists

Synovial infiltration of monocytes is commonly associated with inflammation in rheumatoid arthritis (RA).

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