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  • 1
    Language: English
    In: Annals of the rheumatic diseases, 17 August 2018
    Keywords: Dmards (Biologic) ; Rheumatoid Arthritis ; Tnf-Alpha ; Treatment
    ISSN: 00034967
    E-ISSN: 1468-2060
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  • 2
    Article
    Article
    BMJ Publishing Group Ltd and European League Against Rheumatism
    Language: English
    In: Annals of the Rheumatic Diseases, 27 March 2018
    Description: While biologic disease-modifying antirheumatic drugs (bDMARDs) have transformed outcomes of people with rheumatoid arthritis (RA), a proportion of patients are refractory to multiple bDMARDs. Definitions of refractory RA thus far have been arbitrary, and outcome data and impact of such cohorts remain limited. Extrapolation from randomised controlled trial and some real-life data suggest approximately 20% progress onto a third bDMARD with a more modest proportion failing additional bDMARDs. This viewpoint discusses an opinion of refractory RA disease and proposes key principles to accurately identify refractory cohorts. These include demonstrating presence of persistent inflammation despite multiple therapies and acknowledging development of antidrug antibody. Potential basis of refractory disease is summarised, and suggestions for an initial approach in the future evaluation of refractory disease are offered. Specific investigation of refractory RA disease is necessary to inform the clinical need and provide a basis for robust investigation of underlying mechanisms.
    Keywords: Rheumatoid Arthritis ; Dmards (Biologic) ; Treatment
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 3
    Language: English
    In: The Lancet, 05 May 2012, Vol.379(9827), pp.1682-1684
    Description: Clinicians now aim to diagnose and treat the disease before damage has occurred, and endeavour to treat to a predefi ned target, ideally remission; this has been the aim of treatment for some years but has only been included in international recommendations...
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 4
    Language: English
    In: Annals of the Rheumatic Diseases, 19 February 2014, Vol.73(2), p.420
    Description: The absence of a serological surrogate outcome measure of fibrosis in systemic sclerosis (SSc) is a major deficiency for intervention studies and clinical management. An algorithm including the serum concentration of procollagen-III aminoterminal-propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid, has recently been validated as predictive of severity and clinical outcome in chronic liver diseases (enhanced liver fibrosis (ELF) test) and implemented as a clinical grade test available for physicians. We evaluated the ELF test as a surrogate outcome measure in SSc.
    Keywords: Liver Cirrhosis -- Diagnosis ; Scleroderma, Systemic -- Complications;
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 5
    Language: English
    In: Annals of the Rheumatic Diseases, March, 2014, Vol.73(3), p.A22(1)
    Keywords: Transcription Factors -- Research ; Transcription Factors -- Physiological Aspects ; Rheumatoid Arthritis -- Risk Factors ; Rheumatoid Arthritis -- Research ; Rheumatoid Arthritis -- Genetic Aspects ; Immune Response -- Research
    ISSN: 0003-4967
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  • 6
    Language: English
    In: Annals of the Rheumatic Diseases, 28 July 2017, Vol.76(7), p.1169
    Description: This review assesses the risk assessment of cardiovascular disease (CVD) in rheumatoid arthritis (RA) and how non-invasive imaging modalities may improve risk stratification in future. RA is common and patients are at greater risk of CVD than the general population. Cardiovascular (CV) risk stratification is recommended in European guidelines for patients at high and very high CV risk in order to commence preventative therapy. Ideally, such an assessment should be carried out immediately after diagnosis and as part of ongoing long-term patient care in order to improve patient outcomes. The risk profile in RA is different from the general population and is not well estimated using conventional clinical CVD risk algorithms, particularly in patients estimated as intermediate CVD risk. Non-invasive imaging techniques may therefore play an important role in improving risk assessment. However, there are currently very limited prognostic data specific to patients with RA to guide clinicians in risk stratification using these imaging techniques. RA is associated with increased risk of CV mortality, mainly attributable to atherosclerotic disease, though in addition, RA is associated with many other disease processes which further contribute to increased CV mortality. There is reasonable evidence for using carotid ultrasound in patients estimated to be at intermediate risk of CV mortality using clinical CVD risk algorithms. Newer imaging techniques such as cardiovascular magnetic resonance and CT offer the potential to improve risk stratification further; however, longitudinal data with hard CVD outcomes are currently lacking.
    Keywords: Cardiovascular Disease ; Magnetic Resonance Imaging ; Ultrasonography ; Rheumatoid Arthritis
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 7
    Article
    Article
    BMJ Publishing Group Ltd and European League Against Rheumatism
    Language: English
    In: Annals of the Rheumatic Diseases, 6 June 2011, Vol.70(6), p.886
    Description: Double-blind, randomised controlled studies represent the gold-standard approach to determine the safety and efficacy of therapeutic interventions. In chronic conditions such as rheumatoid arthritis (RA), long-term data are vital to confirm maintenance of effect and identify potential safety signals. The recent introduction of numerous biological therapies for RA has been followed by various long-term extension (LTE) studies. Although useful, the design and method of analysis in such studies vary significantly, partly due to their complexity. This viewpoint highlights general considerations needed when undertaking a LTE study and illustrates the lack of consistency in studies of RA to date. It addresses issues of selection bias, patient discontinuation and missing data. Although used for safety reporting, the lack of adequate powering makes LTE studies of limited benefit. Ethical considerations and challenges are highlighted, including potential conflicts of interest. Finally, the authors suggest the need for consensus to ensure more reliable interpretation and application of data for clinical practice. Following the development of guidelines on reporting of clinical trials in RA and more recently, registry data, a similar approach for LTE studies would be a useful endeavour.
    Keywords: Antirheumatic Agents -- Therapeutic Use ; Arthritis, Rheumatoid -- Drug Therapy ; Randomized Controlled Trials As Topic -- Standards;
    ISSN: 0003-4967
    ISSN: 00034967
    E-ISSN: 1468-2060
    E-ISSN: 14682060
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  • 8
    In: Rheumatology, 2017, Vol. 56(6), pp.882-895
    Description: Cardiac disease is prevalent in SSc and associated with a poor prognosis. Differentiating primary myocardial disease (SSc-cardiomyopathy) from ischaemic heart disease is difficult and the disease phenotype most at risk is unclear. A comprehensive literature review was performed to inform the UK Systemic Sclerosis Study Group for cardiac disease tasked with producing a best practice pathway for the management of cardiac disease in SSc. This review describes the prevalence of SSc-cardiomyopathy, its associated greater mortality and various manifestations (e.g. heart failure, arrhythmias and diastolic dysfunction). The limited evidence suggests SSc-cardiomyopathy is associated with other poor prognostic indicators, including diffuse cutaneous disease, positive SSc-specific serology, black ethnicity, older age at disease onset, tendon friction rubs, abnormal nail-fold capillaroscopy and worse quality-of-life scores. Differentiating SSc-cardiomyopathy from ischaemic heart disease requires well-planned studies. Non-invasive investigative techniques are improving the understanding of its pathophysiological basis.
    Keywords: Systemic Sclerosis ; Scleroderma ; Ssc - Cardiomyopathy ; Primary Myocardial Disease ; Cardiac Disease
    ISSN: 1462-0324
    E-ISSN: 1462-0332
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  • 9
    In: The New England Journal of Medicine, 2014, Vol.371(19), pp.1781-1792
    Description: Background We assessed the effects of reduction and withdrawal of treatment in patients with rheumatoid arthritis who had a remission while receiving etanercept-plus-methotrexate therapy. Methods Patients with early active disease who had not previously received methotrexate or biologic therapy received 50 mg of etanercept plus methotrexate weekly for 52 weeks (open-label phase). We then randomly assigned patients who had qualifying responses at weeks 39 and 52 to receive 25 mg of etanercept plus methotrexate (combination-therapy group), methotrexate alone, or placebo for 39 weeks (double-blind phase). Patients who had qualifying responses at week 39 of the double-blind phase had all treatment withdrawn at that time and were followed to week 65 (treatment-withdrawal phase). The primary end point was the proportion of patients with sustained remission in the double-blind phase. Results Of 306 patients enrolled, 193 underwent randomization in the double-blind phase; 131 qualified for the treatment-withdrawal phase. More patients in the combination-therapy group than in the methotrexate-alone group or the placebo group met the criterion for the primary end point (40 of 63 [63%] vs. 26 of 65 [40%] and 15 of 65 [23%], respectively; P=0.009 for combination therapy vs. methotrexate alone; P〈0.001 for combination therapy vs. placebo). At 65 weeks, 28 patients (44%) who had received combination therapy, 19 (29%) who had received methotrexate alone, and 15 (23%) who had received placebo were in remission (P=0.10 for combination therapy vs. methotrexate alone; P=0.02 for combination therapy vs. placebo; P=0.55 for methotrexate alone vs. placebo). No significant between-group differences were observed in radiographic progression of disease. Serious adverse events were reported in 3 patients (5%) in the combination-therapy group, 2 (3%) in the methotrexate-alone group, and 2 (3%) in the placebo group. Conclusions In patients with early rheumatoid arthritis who had a remission while receiving full-dose etanercept-plus-methotrexate therapy, continuing combination therapy at a reduced dose resulted in better disease control than switching to methotrexate alone or placebo, but no significant difference was observed in radiographic progression. (Funded by Pfizer; ClinicalTrials.gov number, NCT00913458 .) In a randomized trial involving patients with early rheumatoid arthritis who had a response to methotrexate plus 50 mg of etanercept weekly for 52 weeks, continued treatment with methotrexate plus 25 mg of etanercept was more effective than methotrexate alone or placebo. The duration of disease activity in persons with rheumatoid arthritis is an important factor influencing joint destruction and functional disability.1,2 Joint damage frequently begins within weeks or months after the onset of symptoms and is detectable on radiographs within 2 years.3,4 Evidence indicates that early aggressive treatment results in greater improvement than therapy initiated later in the disease course.5–8 Clinical remission, or at least low disease activity, is a critical treatment target in early rheumatoid arthritis, since control of inflammatory processes may limit structural damage and functional impairment.9 High rates of clinical remission, as well as significant . . .
    Keywords: Medicine;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 10
    Language: English
    In: International Journal of Clinical Rheumatology, August, 2012, Vol.7(4), p.425(27)
    Description: Placebo-controlled trials of biological therapies in the treatment of rheumatoid arthritis have demonstrated significant efficacy with acceptable safety profiles. Nevertheless, while biologic treatment is well established, toxicity concerns remain an area of focus; both inter- and intra-class differences in targeted drugs are associated with different safety issues. Understanding these is important to guide therapy choice in the context of disease characteristics and comorbidity. Long-term safety data for the earliest introduced biologics (TNF-[alpha] inhibitors; infliximab, etanercept and adalimumab) are becoming available from large observational cohorts, such as national registries, and will be discussed in this review. For the more recently available treatments (certolizumab pegol, golimumab, rituximab, tocilizumab and abatacept), data from long-term extension studies of trials will be examined.
    Keywords: Rheumatoid Arthritis -- Care And Treatment ; Tumors -- Care And Treatment ; Comorbidity -- Care And Treatment ; Antirheumatic Agents ; Tumor Necrosis Factor ; Rheumatoid Factor ; Drugs
    ISSN: 1758-4272
    E-ISSN: 17584280
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