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Rheumatoid Arthritis: HELP
Articles from Radboud University
Based on 243 articles published since 2008
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These are the 243 published articles about Arthritis, Rheumatoid that originated from Radboud University during 2008-2019.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7 · 8 · 9 · 10
1 Guideline [Practice guideline 'Diagnosis and treatment of rheumatoid arthritis']. 2009

Schipper, Lydia G / Hoekstra, Monique / Vliet Vlieland, Thea P M / Jansen, Tim L / Lems, Willem F / van Riel, Piet L C M / Anonymous5530647. ·Universitair Medisch Centrum St Radboud, afdeling Reumatologie, Nijmegen, The Netherlands. ·Ned Tijdschr Geneeskd · Pubmed #20051161.

ABSTRACT: Treatment early in the course of the disease, along with early diagnosis, has a positive influence on clinical outcome in patients with rheumatoid arthritis (RA). Therapeutic strategies, including the use of 'disease-modifying antirheumatic drug' (DMARD) combinations, have proved effective, with relatively few side effects. New insights into the pathophysiology of RA have lead to the development of novel therapeutic agents that have been demonstrated to be highly effective. Patients should be monitored intensively with respect to the effect of therapy on reduction of disease activity, followed by modification of therapeutic strategy in the case of a suboptimal treatment response. Various non-pharmacological interventions, such as exercise therapy and patient education, are available to help patients to cope with the consequences of the disease. Optimizing treatment of RA by means of this approach will help to realize the goal of current therapy: to achieve and sustain remission and, thereby, an optimal functional level.

2 Editorial Cross-talk between bone morphogenetic proteins and inflammatory pathways. 2015

van der Kraan, Peter M / Davidson, Esmeralda N Blaney. ·Experimental Rheumatology, Department of Rheumatology, Radboudumc, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands. Peter.vanderkraan@radboudumc.nl. · Experimental Rheumatology, Department of Rheumatology, Radboudumc, Geert Grooteplein 26, 6525 GA, Nijmegen, The Netherlands. Esmeralda.blaneydavidson@radboudumc.nl. ·Arthritis Res Ther · Pubmed #26592526.

ABSTRACT: Pro-inflammatory cytokines and bone morphogenetic proteins are generally studied separately and considered to be elements of different worlds, immunology and developmental biology. Varas and colleagues report that these factors show cross-talk in rheumatoid arthritis synoviocytes. They show that pro-inflammatory cytokines not only stimulate the production of bone morphogenetic proteins but that these endogenously produced bone morphogenetic proteins interfere with the effects of pro-inflammatory cytokines on synoviocytes.

3 Editorial Enhanced cardiovascular risk in rheumatoid arthritis: elucidation, assessment, and management. 2015

Dessein, Patrick H / Semb, Anne G / González-Gay, Miguel A / Popa, Calin D. ·Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa. · Preventive Cardio-Rheuma Clinic, Department of Rheumatology, Diakonhjemmet Hospital, 0370 Oslo, Norway. · Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa ; Department of Rheumatology, Hospital Universitario Marques de Valdecilla, IDIVAL, 39008 Santander, Spain. · Department of Rheumatology, Radboud University Nijmegen Medical Centre, 6525 Nijmegen, Netherlands. ·Biomed Res Int · Pubmed #25861648.

ABSTRACT: -- No abstract --

4 Review Implementation of the EULAR cardiovascular risk management guideline in patients with rheumatoid arthritis: results of a successful collaboration between primary and secondary care. 2018

Weijers, Julia M / Rongen-van Dartel, Sanne A A / Hoevenaars, Dan M G M F / Rubens, Max / Hulscher, Marlies E J L / van Riel, Piet L C M. ·IQ Healthcare, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands. · Department of Rheumatology, Bernhoven, Uden, The Netherlands. · Synchroon, Uden-Oss-Veghel, The Netherlands. · General Practice, Schijndel, The Netherlands. ·Ann Rheum Dis · Pubmed #29167154.

ABSTRACT: The updated European League Against Rheumatism (EULAR) guideline recommends cardiovascular disease (CVD) risk assessment at least once every 5 years in all patients with rheumatoid arthritis (RA). This viewpoint starts with a literature overview of studies that investigated the level of CVD risk factor (CVD-RF) screening in patients with RA in general practices or in outpatient clinics. These studies indicate that CVD-RF screening in patients with RA is marginally applied in clinical practice, in primary as well as secondary care. Therefore, the second part of this viewpoint describes an example of the successful implementation of the EULAR cardiovascular disease risk management (CVRM) guideline in patients with RA in a region in the south of the Netherlands where rheumatologists and general practitioners (GPs) closely collaborate to manage the cardiovascular risk of patients with RA. The different components of this collaboration and the responsibilities of respectively primary and secondary care professionals are described. Within this collaboration, lipid profile was used as an indicator to assess whether CVD-RF screening was performed in the previous 5 years. In 72% (n=454) of the 628 patients with RA, a lipid profile was determined in the previous 5 years. As part of routine quality control, a reminder was sent to the GP in case a patient with RA was not screened. After sending the reminder letter, in 88% of all patients with RA, CVD risk assessment was performed. This collaboration can be seen as good practice to provide care in line with the EULAR guideline.

5 Review Synovial tissue research: a state-of-the-art review. 2017

Orr, Carl / Vieira-Sousa, Elsa / Boyle, David L / Buch, Maya H / Buckley, Christopher D / Cañete, Juan D / Catrina, Anca I / Choy, Ernest H S / Emery, Paul / Fearon, Ursula / Filer, Andrew / Gerlag, Danielle / Humby, Frances / Isaacs, John D / Just, Søren A / Lauwerys, Bernard R / Le Goff, Benoit / Manzo, Antonio / McGarry, Trudy / McInnes, Iain B / Najm, Aurélie / Pitzalis, Constantino / Pratt, Arthur / Smith, Malcolm / Tak, Paul P / Thurlings, Rogier / Fonseca, João E / Veale, Douglas J / Tas, Sander W. ·Centre for Arthritis and Rheumatic Disease, University College Dublin, Dublin Academic Medical Centre, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland. · Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-035, Lisbon, Portugal. · University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, California 92093, USA. · Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. · Rheumatology Research Group, University of Birmingham, Edgbaston, Birmingham, West Midlands B15 2TT, UK. · Arthritis Unit, Rheumatology Department, Hospital Clínic, IDIBAPS, Villarroel, 170, 08036 Barcelona, Spain. · Rheumatology Unit, Department of Medicine (Solna), Karolinska Institute and Karolinska University Hospital, 171 76 Stockholm, Sweden. · Cardiff University School of Medicine, Institute of Infection and Immunity, 1 st Floor, Tenovus Building, Heath Park, Cardiff CF14 4XN, UK. · Department of Molecular Rheumatology, Trinity College Dublin, University of Dublin, College Green, Dublin 2, Ireland. · Department of Clinical Immunology &Rheumatology, Amsterdam Rheumatology and Immunology Centre, Academic Medical Centre, University of Amsterdam, Room F4-105, POBox 22700, 1100 DE, Amsterdam, Netherlands. · Clinical Unit Cambridge, GlaxoSmithKline, Cambridge, UK. · Centre for Experimental Medicine and Rheumatology, John Vane Science Centre, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. · Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK. · Department of Medicine, Svendborg Hospital, Odense University Hospital, Valdemarsgade 53, 5700 Svendborg, Denmark. · Université catholique de Louvain and Department of Rheumatology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Bruxelles, Belgium. · Rheumatology Unit, Nantes University Hospital, Hôtel-Dieu, 1, place Alexis-Ricordeau, 44093 Nantes cedex 1, France. · Rheumatology and Translational Immunology Research Laboratories (LaRIT), Division of Rheumatology, IRCCS Policlinico San Matteo Foundation/University of Pavia, P.le Golgi 19, 27100 Pavia, Italy. · Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary and Life Sciences University of Glasgow, 120 University Avenue, Glasgow G12 8TA, UK. · Rheumatology, Flinders University, GPO Box 2100, Adelaide 5001, South Australia, Australia. · GlaxoSmithKline, Cambridge, UK. · Institute for Molecular Life Sciences, RadboudUMC, Theodoor Craanenlaan 11, Nijmegen 6525 GA, Netherlands. ·Nat Rev Rheumatol · Pubmed #28701760.

ABSTRACT: The synovium is the major target tissue of inflammatory arthritides such as rheumatoid arthritis. The study of synovial tissue has advanced considerably throughout the past few decades from arthroplasty and blind needle biopsy to the use of arthroscopic and ultrasonographic technologies that enable easier visualization and improve the reliability of synovial biopsies. Rapid progress has been made in using synovial tissue to study disease pathogenesis, to stratify patients, to discover biomarkers and novel targets, and to validate therapies, and this progress has been facilitated by increasingly diverse and sophisticated analytical and technological approaches. In this Review, we describe these approaches, and summarize how their use in synovial tissue research has improved our understanding of rheumatoid arthritis and identified candidate biomarkers that could be used in disease diagnosis and stratification, as well as in predicting disease course and treatment response.

6 Review Influence of route of administration/drug formulation and other factors on adherence to treatment in rheumatoid arthritis (pain related) and dyslipidemia (non-pain related). 2017

Fautrel, Bruno / Balsa, Alejandro / Van Riel, Piet / Casillas, Marta / Capron, Jean-Philippe / Cueille, Carine / de la Torre, Inmaculada. ·a Pierre et Marie Curie University, Sorbonne Universités ; and Rheumatology Department, Pitié Salpêtrière Hospital , Paris , France. · b Rheumatology Department and Health Research Institute (Idipaz) , Hospital Universitario de La Paz , Madrid , Spain. · c Scientific Institute for Quality of Healthcare, Radboud University Medical Center , Nijmegen , and Department of Rheumatology , Bernhoven, Uden , The Netherlands. · d Lilly SA, Alcobendas , Madrid , Spain. · e Lilly France , Neuilly-sur-Seine , France. ·Curr Med Res Opin · Pubmed #28358217.

ABSTRACT: OBJECTIVES: A comprehensive review was performed to investigate the effect of route of administration on medication adherence and persistence in rheumatoid arthritis (RA) and to compare adherence/persistence with oral medications between RA and a non-painful disease (dyslipidemia). RESEARCH DESIGN AND METHODS: Comprehensive database searches were performed to identify studies investigating medication adherence and/or persistence in adults with RA receiving conventional synthetic or biologic agents. Similar searches were performed for studies of patients with dyslipidemia receiving statins. Studies had to be published after 1998 in English and involve ≥6 months' follow up. MAIN OUTCOME MEASURES: Adherence and persistence were compared between the different routes of drug administration in RA, and between the two diseases for oral medications. RESULTS: A total of 35 and 28 papers underwent data extraction for RA and dyslipidemia, respectively. Within the constraints of the analysis, adherence and persistence rates appeared broadly similar for the different routes of drug administration in RA. Adherence to oral medications was also broadly similar across the two diseases, but persistence was lower in dyslipidemia. Poor adherence has clinical consequences in both diseases: greater disease activity and risk of flare in RA, and increased serum cholesterol levels and risk of heart and cerebrovascular disease in dyslipidemia. Over 1-3 years, poor adherence to biologic RA medications led to increased resource use and medical costs but lower total direct costs due to reduced biologic drug costs. Conversely, poor adherence to dyslipidemia medications resulted in increased total direct costs. In both diseases, adherence improved with patient education/support. CONCLUSIONS: The route of drug administration and the symptomatic (pain) nature of the disease do not appear to be dominant factors for drug adherence or persistence in RA. LIMITATION: The wide range of adherence and persistence values and definitions across studies made comparisons between drug formulations and diseases difficult.

7 Review Little Evidence for Usefulness of Biomarkers for Predicting Successful Dose Reduction or Discontinuation of a Biologic Agent in Rheumatoid Arthritis: A Systematic Review. 2017

Tweehuysen, Lieke / van den Ende, Cornelia H / Beeren, Fenna M M / Been, Evelien M J / van den Hoogen, Frank H J / den Broeder, Alfons A. ·Sint Maartenskliniek, Nijmegen, The Netherlands. · Sint Maartenskliniek and Radboud University Medical Center, Nijmegen, The Netherlands. ·Arthritis Rheumatol · Pubmed #27696778.

ABSTRACT: OBJECTIVE: To systematically review studies addressing prediction of successful dose reduction or discontinuation of a biologic agent in rheumatoid arthritis (RA). METHODS: PubMed, Embase, and Cochrane Library databases were searched for studies that examined the predictive value of biomarkers for successful dose reduction or discontinuation of a biologic agent in RA. Two reviewers independently selected studies, and extracted data and assessed the risk of bias. A biomarker was classified as a "potential predictor" if the univariate association was either strong (odds ratio or hazard ratio >2.0 or <0.5) or statistically significant. For biomarkers that were studied multiple times, qualitative best-evidence synthesis was performed separately for the prediction of successful dose reduction and discontinuation. Biomarkers that were defined in ≥75% of the studies as potential predictors were regarded as "predictor" for the purposes of our study. RESULTS: Of 3,029 nonduplicate articles initially searched, 16 articles regarding 15 cohorts were included in the present study. Overall, 17 biomarkers were studied multiple times for the prediction of successful dose reduction, and 33 for the prediction of successful discontinuation of a biologic agent. Three predictors were identified: higher adalimumab trough level for successful dose reduction and lower Sharp/van der Heijde erosion score and shorter symptom duration at the start of a biologic agent for successful discontinuation. CONCLUSION: The predictive value of a wide variety of biomarkers for successful dose reduction or discontinuation of biologic treatment in RA has been investigated. We identified only 3 biomarkers as predictors, in just 2 studies. The strength of the evidence is limited by the low quality of the included studies and the likelihood of reporting bias and multiple testing.

8 Review The Disease Activity Score (DAS) and the Disease Activity Score using 28 joint counts (DAS28) in the management of rheumatoid arthritis. 2016

van Riel, Piet L C M / Renskers, Lisanne. ·Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen; and Department of Rheumatology, Bernhoven, Uden, The Netherlands. piet.vanriel@radboudumc.nl. · Department of Rheumatology, Bernhoven, Uden, The Netherlands. ·Clin Exp Rheumatol · Pubmed #27762189.

ABSTRACT: In rheumatoid arthritis (RA), disease activity cannot be measured in all individual patients according to a single variable. The Disease Activity Score (DAS) and the DAS28 have been developed to measure disease activity in RA both in daily clinical practice as well as in clinical trials on a group as well as individual level. The DAS/DAS28 is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and general health. The DAS-based EULAR response criteria were primarily developed to be used in clinical trials. The EULAR response criteria classify individual patients as non-, moderate, or good responders, dependent on the magnitude of change and level of disease activity reached. In addition, already in the early nineties, cut points were developed to categorise patients in remission. The DAS28 is incorporated in several electronic patient records and web-based systems for monitoring purposes in daily clinical practice. In addition to this, it is being used in combination with patient-reported outcome measures (PROMs) to facilitate self-monitoring.

9 Review Secukinumab for rheumatology: development and its potential place in therapy. 2016

Koenders, Marije I / van den Berg, Wim B. ·Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. ·Drug Des Devel Ther · Pubmed #27445458.

ABSTRACT: Rheumatic disease is not a single disorder, but a group of more than 100 diseases that affect joints, connective tissues, and/or internal organs. Although rheumatic diseases like rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis (AS) differ in their pathogenesis and clinical presentation, the treatment of these inflammatory disorders overlaps. Non-steroid anti-inflammatory drugs are used to reduce pain and inflammation. Additional disease-modifying anti-rheumatic drugs are prescribed to slowdown disease progression, and is in RA more frequently and effectively applied than in AS. Biologicals are a relatively new class of treatments that specifically target cytokines or cells of the immune system, like tumor necrosis factor alpha inhibitors or B-cell blockers. A new kid on the block is the interleukin-17 (IL-17) inhibitor secukinumab, which has been recently approved by the US Food and Drug Administration for moderate-to-severe plaque psoriasis, psoriatic arthritis, and AS. IL-17 is a proinflammatory cytokine that has an important role in host defense, but its proinflammatory and destructive effects have also been linked to pathogenic processes in autoimmune diseases like RA and psoriasis. Animal models have greatly contributed to further insights in the potential of IL-17 blockade in autoimmune and autoinflammatory diseases, and have resulted in the development of various potential drugs targeting the IL-17 pathway. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to IL-17A and recently entered the market under the brand name Cosentyx(®). By binding to IL-17A, secukinumab prevents it from binding to its receptor and inhibits its ability to trigger inflammatory responses that play a role in the development of various autoimmune diseases. With secukinumab being the first in class to receive Food and Drug Administration approval, this article will further focus on this new biologic agent and review the milestones in its development and marketing.

10 Review Quality in rheumatoid arthritis care. 2015

Mahmood, Sehrash / Lesuis, Nienke / van Tuyl, Lilian H D / van Riel, Piet / Landewé, Robert. ·Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Department of Rheumatology, Room ZH 3A-58, De boelelaan 1117, 1081, HV, Amsterdam, The Netherlands. Electronic address: s.mahmood@vumc.nl. · Sint Maartenskliniek, Department of Rheumatology, Hengstdal 3, 6500, GM, Nijmegen, The Netherlands. Electronic address: n.lesuis@maartenskliniek.nl. · Amsterdam Rheumatology and Immunology Center, VU University Medical Center, Department of Rheumatology, Room ZH 3A-56, De boelelaan 1117, 1081, HV, Amsterdam, The Netherlands. Electronic address: l.vantuyl@vumc.nl. · Radboud University Medical Center, Radboud Institute for Health Sciences, IQ Healthcare, P.O. Box 9101, 6500, HB, Nijmegen, The Netherlands. Electronic address: Piet.vanriel@radboudumc.nl. · Amsterdam Rheumatology and Immunology Center, Academic Medical Center, Meibergdreef 9, The Netherlands. Electronic address: landewe@rlandewe.nl. ·Best Pract Res Clin Rheumatol · Pubmed #26697773.

ABSTRACT: While most rheumatology practices are characterized by strong commitment to quality of care and continuous improvement to limit disability and optimize quality of life for patients and their families, the actual step toward improvement is often difficult. This is because there are still barriers to be addressed and facilitators to be captured before a satisfying and cost-effective practice management is installed. Therefore, this review aims to assist practicing rheumatologists with quality improvement of their daily practice, focusing on care for rheumatoid arthritis (RA) patients. First we define quality of care as "the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge". Often quality is determined by the interplay between structure, processes, and outcomes of care, which is also reflected in the corresponding indicators to measure quality of care. Next, a brief overview is given of the current treatment strategies used in RA, focusing on the tight control strategy, since this strategy forms the basis of international treatment guidelines. Adherence to tight control strategies leads, also in daily practice, to better outcomes in patients with regard to disease control, functional status, and work productivity. Despite evidence in favor of tight control strategies, adherence in daily practice is often challenging. Therefore, the next part of the review focuses on possible barriers and facilitators of adherence, and potential interventions to improve quality of care. Many different barriers and facilitators are known and targeting these can be effective in changing care, but these effects are rather small to moderate. With regard to RA, few studies have tried to improve care, such as a study aiming to increase the number of disease activity measures done by a combination of education and feedback. Two out of the three studies showed markedly positive effects of their interventions, suggesting that change is possible. Finally, a simple step-by-step plan is described, which could be used by rheumatologists in daily practice wanting to improve their RA patient care.

11 Review Patient-centred care in established rheumatoid arthritis. 2015

Voshaar, M J H / Nota, I / van de Laar, M A F J / van den Bemt, B J F. ·University of Twente, Enschede, The Netherlands. Electronic address: m.j.h.voshaar@utwente.nl. · University of Twente, Enschede, The Netherlands. Electronic address: i.nota@utwente.nl. · University of Twente, Enschede, The Netherlands; Medisch Spectrum Twente, Enschede, The Netherlands. Electronic address: M.vandeLaar@mst.nl. · Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands; Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: b.vandenbemt@maartenskliniek.nl. ·Best Pract Res Clin Rheumatol · Pubmed #26697772.

ABSTRACT: Review of the evidence on patient-centred care (PCC) in rheumatoid arthritis (RA) shows that involving the patient as an individual - with unique needs, concerns and preferences - has a relevant impact on treatment outcomes (safety, effectiveness and costs). This approach empowers patients to take personal responsibility for their treatment. Because clinicians are only able to interact personally with their patients just a few hours per year, patients with a chronic condition such as RA should be actively involved in the management of their disease. To stimulate this active role, five different PCC activities can be distinguished: (1) patient education, (2) patient involvement/shared decision-making, (3) patient empowerment/self-management, (4) involvement of family and friends and (5) physical and emotional support. This article reviews the existing knowledge on these five PCC activities in the context of established RA management, especially focused on opportunities to increase medication adherence in established RA.

12 Review Flare Rate in Patients with Rheumatoid Arthritis in Low Disease Activity or Remission When Tapering or Stopping Synthetic or Biologic DMARD: A Systematic Review. 2015

Kuijper, T Martijn / Lamers-Karnebeek, Femke B G / Jacobs, Johannes W G / Hazes, Johanna M W / Luime, Jolanda J. ·From the Department of Rheumatology, Erasmus Medical Center, Rotterdam; Department of Rheumatology, Radboud University Medical Center, Nijmegen; Department of Rheumatology and Clinical Immunology, University Medical Center, Utrecht, the Netherlands.T.M. Kuijper, MD, MSc, Department of Rheumatology, Erasmus Medical Center; F.B. Lamers-Karnebeek, MD, Department of Rheumatology, Radboud University Medical Center; J.W. Jacobs, MD, PhD, Department of Rheumatology and Clinical Immunology, University Medical Center; J.M. Hazes, MD, PhD, Department of Rheumatology, Erasmus Medical Center; J.J. Luime, PhD, Department of Rheumatology, Erasmus Medical Center. ·J Rheumatol · Pubmed #26428204.

ABSTRACT: OBJECTIVE: To evaluate the risk of having a disease flare in patients with rheumatoid arthritis (RA) with low disease activity (LDA) or in remission when deescalating (tapering or stopping) disease-modifying antirheumatic drug (DMARD) therapy. METHODS: A search in medical databases including publications from January 1950 to February 2015 was performed. Included were trials and observational studies in adults with RA who were in LDA or remission, evaluating ≥ 20 patients tapering or stopping DMARD. Flare rates had to have been reported. A metaanalysis was performed on studies deescalating tumor necrosis factor (TNF) blockers. RESULTS: Four studies evaluated synthetic DMARD. Flare rates ranged from 8% at 24 weeks to 63% at 4 months after deescalation. Fifteen studies reported on TNF blockers. Estimated flare rates by metaanalysis on studies tapering or stopping TNF blockers were 0.26 (95% CI 0.17-0.39) and 0.49 (95% CI 0.27-0.73) for good-quality and moderate-quality studies, respectively. Flare rates in 3 studies stopping tocilizumab were 41% after 6 months, 55% at 1 year, and 87% at 1 year. Flare rates in 3 studies deescalating abatacept were 34% at 1 year, 41% at 1 year, and 72% at 6 months. Five studies evaluating radiographic progression in patients deescalating treatment all found limited to no progression. CONCLUSION: Results suggest that more than one-third of patients with RA with LDA or in remission may taper or stop DMARD treatment without experiencing a disease flare within the first year. Dose reduction of TNF blockers results in lower flare rates than stopping and may be noninferior to continuing full dose. Radiological progression after treatment deescalation remains low, but may increase slightly.

13 Review What do we know about rheumatoid arthritis patients' support needs for self-management? A scoping review. 2015

Zuidema, R M / Repping-Wuts, H / Evers, A W M / Van Gaal, B G I / Van Achterberg, T. ·Radboud university medical center, Radboud Institute for Health Science, Scientific Institute for Quality of Healthcare (IQ healthcare), Nijmegen, The Netherlands. Electronic address: rixt.zuidema@radboudumc.nl. · Radboud university medical center, Department of Rheumatology, Radboud Institute for Health Science, Nijmegen, The Netherlands. · University of Leiden, Department of Health, Medical and Neuropsychology, The Netherlands; Radboud university medical center, Department of Medical Psychology, Nijmegen, The Netherlands. · Radboud university medical center, Radboud Institute for Health Science, Scientific Institute for Quality of Healthcare (IQ healthcare), Nijmegen, The Netherlands. · KU Leuven, Centre for Health Services and Nursing Research, Leuven, Belgium; Radboud university medical center, Radboud Institute for Health Science, Scientific Institute for Quality of Healthcare (IQ healthcare), Nijmegen, The Netherlands. ·Int J Nurs Stud · Pubmed #26117711.

ABSTRACT: BACKGROUND: Self-management support is essential to perform self-management behavior. To provide this support in an effective way, insight in the needs for self-management support is necessary. OBJECTIVE: To give an overview of self-management support needs from the perspective of rheumatoid arthritis patients to help nurses to improve self-management. DESIGN: We conducted a scoping review for the period of January 2002 to May 2013 using the following inclusion criteria: (1) studies on adult patients aged 18 years and older, (2) studies from the perspective of rheumatoid arthritis patients, (3) studies reporting results on support needs, and (4) empirical studies using any design. DATA SOURCES: We searched in PubMed, CINAHL, and PsycINFO. REVIEW METHODS: Following the steps of a scoping review, we (1) identified the research question, (2) identified relevant studies, (3) selected studies, (4) charted the data, and (5) collated, summarized, and reported results. We incorporated the optional sixth step of consultation of a multidisciplinary panel of professionals and patients to validate our findings. RESULTS: Seventeen articles were included. Our review shows that rheumatoid arthritis patients have informational, emotional, social and practical support needs. We found an information need for various topics, e.g. exercises and medication. Patients express a need for emotional support in daily life, given through other RA patients, colleagues and supervisors and nurses. For information needs, emotional and social support it is important that it is tailored to the individual needs of the patient. CONCLUSION: The most important support needs for self-management mentioned by rheumatoid arthritis patients are more informational, social and practical support and emotional support. Considering patients' perspective as a starting point for delivering support for self-management can lead to the development of nursing interventions tailored to the needs of rheumatoid arthritis patients.

14 Review Toll-like receptor mediated modulation of T cell response by commensal intestinal microbiota as a trigger for autoimmune arthritis. 2015

Rogier, Rebecca / Koenders, Marije I / Abdollahi-Roodsaz, Shahla. ·Experimental Rheumatology, Radboud University Medical Center, 6500 HB Nijmegen, Netherlands. ·J Immunol Res · Pubmed #25802876.

ABSTRACT: In autoimmune diseases, a disturbance of the balance between T helper 17 (Th17) and regulatory T cells (Tregs) is often observed. This disturbed balance is also the case in rheumatoid arthritis (RA). Genetic predisposition to RA confers the presence of several polymorphisms mainly regulating activation of T lymphocytes. However, the presence of susceptibility factors is neither necessary nor sufficient to explain the disease development, emphasizing the importance of environmental factors. Multiple studies have shown that commensal gut microbiota is of great influence on immune homeostasis and can trigger the development of autoimmune diseases by favoring induction of Th17 cells over Tregs. However the mechanism by which intestinal microbiota influences the Th cell balance is not completely understood. Here we review the current evidence supporting the involvement of commensal intestinal microbiota in rheumatoid arthritis, along with a potential role of Toll-like receptors (TLRs) in modulating the relevant Th cell responses to trigger autoimmunity. A better understanding of TLR triggering by intestinal microbiota and subsequent T cell activation might offer new perspectives for manipulating the T cell response in RA patients and may lead to the discovery of new therapeutic targets or even preventive measures.

15 Review Novel therapeutic targets in rheumatoid arthritis. 2015

Koenders, Marije I / van den Berg, Wim B. ·Radboud University Medical Center, Experimental Rheumatology, Nijmegen, The Netherlands. Electronic address: Marije.Koenders@radboudumc.nl. · Radboud University Medical Center, Experimental Rheumatology, Nijmegen, The Netherlands. ·Trends Pharmacol Sci · Pubmed #25732812.

ABSTRACT: Rheumatoid arthritis (RA) is an autoimmune disease that leads to inflammation and destruction of synovial joints. Despite the broad spectrum of antirheumatic drugs, this heterogeneous disease is still not well controlled in up to 30% of patients. Here, we discuss two pathways that are regarded as interesting novel therapeutic targets in the field of rheumatology: the Janus kinase (JAK) pathway and the T helper-17 (Th17) pathway [including interleukin (IL)-17, IL-21, IL-22, and granulocyte-macrophage colony-stimulating factor (GM-CSF)]. We also review the therapy potential of biologicals and small-molecule inhibitors blocking these pathways. Advances in combination therapy in addition to progress in biomarker screening will help us to further achieve effective and personalized healthcare for patients with RA.

16 Review The role of the Th17 cytokines IL-17 and IL-22 in Rheumatoid Arthritis pathogenesis and developments in cytokine immunotherapy. 2015

Roeleveld, Debbie M / Koenders, Marije I. ·Radboud University Medical Center, Experimental Rheumatology, Department of Rheumatology, Geert Grooteplein 26-28, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Debbie.Roeleveld@radboudumc.nl. · Radboud University Medical Center, Experimental Rheumatology, Department of Rheumatology, Geert Grooteplein 26-28, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Electronic address: Marije.Koenders@radboudumc.nl. ·Cytokine · Pubmed #25466295.

ABSTRACT: Over the past few years, the importance of Interleukin (IL)-17 and T helper (Th)17 cells in the pathology of Rheumatoid Arthritis (RA) has become apparent. RA is a systemic autoimmune disease that affects up to 1% of the population worldwide. It is characterized by an inflamed, hyperplastic synovium with pannus formation, leading to bone and cartilage destruction in the joints. By the production of effector cytokines like IL-17 and IL-22, the T helper 17 subset protects the host against bacterial and fungal infections, but it can also promote the development of various autoimmune diseases like RA. Hence, the Th17 pathway recently became a very interesting target in RA treatment. Up to now, several therapies targeting the Th17 cells or its effector cytokines have been tested, or are currently under investigation. This review clarifies the role of Th17 cells and its cytokines in the pathogenesis of RA, and provides an overview of the clinical trials using immunotherapy to target this particular T helper subset or the two main effector cytokines by which the Th17 cells exert their function, IL-17 and IL-22.

17 Review Optimizing the expediency of TNFi in rheumatoid arthritis: offering a TNFi holiday in patients having reached low-disease activity in the maintenance phase. 2014

van Ingen, Iris L A / Lamers-Karnebeek, Femke / Jansen, Tim L. ·Radboud University Medical Center, Department of Rheumatology , POB 9101, 6500 HB Nijmegen , The Netherlands Tim.Jansen@Radboudumc.nl. ·Expert Opin Biol Ther · Pubmed #25366268.

ABSTRACT: INTRODUCTION: The treatment of rheumatoid arthritis (RA) has been revolutionized since the introduction of biological disease-modifying antirheumatic drugs such as tumour necrosis factor alpha inhibitors (TNFi), and clinical remission has become a realistic target in the treatment strategy. Discontinuation strategies of TNFi therapy after reaching sustained remission or low-disease activity (LDA) have been emerging. These strategies are important considering the risk-benefit profile of TNFi, as well as looking at them from a cost-economic point of view. AREAS COVERED: This article presents an overview of recent major studies on TNFi withdrawal, and tapering and about the safety of doing so. EXPERT OPINION: Although data are still limited, tapering or discontinuing TNFi in some RA patients may well be possible, especially in the early RA patients who are methotrexate naive. Also, a substantial group of longer established RA patients can stop or taper TNFi, particularly when ultrasonography signals are negative. However, before making the decision of implementing it in the routine care for RA patients, more predictors for successful discontinuation are desired.

18 Review The development of the disease activity score (DAS) and the disease activity score using 28 joint counts (DAS28). 2014

van Riel, P L C M. ·Scientific Institute for Quality of Healthcare, Radboud University Medical Center, Nijmegen, The Netherlands. piet.vanriel@radboudumc.nl. ·Clin Exp Rheumatol · Pubmed #25365092.

ABSTRACT: In rheumatoid arthritis, disease activity cannot be measured using a single variable. The Disease Activity Score (DAS) has been developed as a quantitative index to be able to measure, study and manage disease activity in RA in daily clinical practice, clinical trials, and long term observational studies. The DAS is a continuous measure of RA disease activity that combines information from swollen joints, tender joints, acute phase response and patient self-report of general health. Cut points were developed to classify patients in remission, as well as low, moderate, and severe disease activity in the 1990s. DAS-based EULAR response criteria were primarily developed to be used in clinical trials to classify individual patients as non-, moderate, or good responders, depending on the magnitude of change and absolute level of disease activity at the conclusion of the test.

19 Review Cardiovascular case fatality in rheumatoid arthritis is decreasing; first prospective analysis of a current low disease activity rheumatoid arthritis cohort and review of the literature. 2014

Meek, Inger L / Vonkeman, Harald E / van de Laar, Mart A F J. ·Arthritis Center Twente, University Twente and Medisch Spectrum Twente, 7500KA Enschede, Netherlands. i.meek@reuma.umcn.nl. ·BMC Musculoskelet Disord · Pubmed #24779371.

ABSTRACT: BACKGROUND: Previous studies found increased case fatality after myocardial infarction and more frequent sudden death in RA patients compared to non-RA subjects. The RA associated CV risk might be explained by the combined effects of chronic systemic inflammation and increased lifestyle associated cardiovascular risk factors, and modified by the use of medication such as non steroidal anti-inflammatory drugs, corticosteroids and disease modifying anti-rheumatic drugs. Trends in case fatality rate in RA after the introduction of potent anti-inflammatory biologic therapies and treat-to-target treatment strategies aiming at remission are not known. This study was performed to examine the cardiovascular fatality rate in current low disease activity RA, and to evaluate trends in RA associated CV case fatality over time. METHODS: Prospective study to determine the incidence of fatal and nonfatal CV events in 480 RA patients included in the ACT-CVD cohort between February 2009 and December 2011. Patients with prior CV disease were excluded. Cox regression analysis was performed to determine CV event risk and contributing risk factors over time. The results of the cohort analysis were put into the context of a review of the literature to evaluate trends in RA associated CV fatality rate over time. RESULTS: The study included 480 RA patients, 72.3% female with median disease duration of 4.2 years, 72.1% being in clinical remission (Disease Activity Score in 28 joints). During a mean follow up of 2.9 years 29 patients (6%) experienced a first CV event, 2 fatal and 27 non-fatal, corresponding to a 6.9% case fatality rate. Comparison with previous studies in cohorts with successive enrolment periods shows a trend towards a decrease in CV case fatality in RA from 52.9% in 1998 to 6.9% in our study. CONCLUSION: CV case fatality in current low disease activity RA is importantly lower than in previous studies, and a trend towards decreasing CV fatality in RA is suggested.

20 Review Burden of disease in treated rheumatoid arthritis patients: going beyond the joint. 2014

Cutolo, Maurizio / Kitas, George D / van Riel, Piet L C M. ·Research Laboratories and Academic Division of Clinical Rheumatology, Department of Internal Medicine, University of Genoa, Viale Benedetto XV 6, Genoa 16132, Italy. Electronic address: mcutolo@unige.it. · Clinical Rheumatology and R&D Director, Department of Rheumatology, Dudley Group NHS Foundation Trust, Dudley, United Kingdom; and Arthritis Research UK Epidemiology Unit, University of Manchester, Manchester, UK. · Rheumatology, Department of Rheumatology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. ·Semin Arthritis Rheum · Pubmed #24080116.

ABSTRACT: OBJECTIVE: The disease burden in rheumatoid arthritis (RA) extends beyond the joint. This article evaluates the physical and psychosocial extra-articular burden of treated RA and relationships among diverse disease manifestations. METHODS: MEDLINE searches identified papers published in English from January 2003 to December 2012 that evaluated systemic complications and psychosocial aspects associated with RA. Preference was given to studies with randomized cohorts and large (>100) sample sizes. Of 378 articles identified in the initial search, 118 were selected for inclusion. RESULTS: RA is associated with multiple comorbidities and psychosocial impairments, including cardiovascular disease, osteoporosis, interstitial lung disease, infection, malignancies, fatigue, depression, cognitive dysfunction, reduced work performance, work disability, and decreased health-related quality of life. The etiology of the extra-articular burden may reflect the systemic inflammation and immune system alteration associated with RA, metabolic imbalances and side effects related to treatment, or the influence of comorbidities. Strategies that may help to reduce the extra-articular disease burden include personalized medicine and the potential introduction of treatments with new mechanisms of action. CONCLUSION: Despite improvements in treating joint disease, the extra-articular burden in RA remains substantial, encompassing multiple comorbidities and psychosocial impairments.

21 Review Treating inflammation by blocking interleukin-1 in humans. 2013

Dinarello, Charles A / van der Meer, Jos W M. ·Department of Medicine, University of Colorado Denver, Aurora, CO, United States; Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. · Department of Medicine, Radboud University Medical Center, Nijmegen, The Netherlands. ·Semin Immunol · Pubmed #24275598.

ABSTRACT: IL-1 is a master cytokine of local and systemic inflammation. With the availability of specific IL-1 targeting therapies, a broadening list of diseases has revealed the pathologic role of IL-1-mediated inflammation. Although IL-1, either IL-1α or IL-1β, was administered to patients in order to improve bone marrow function or increase host immune responses to cancer, these patients experienced unacceptable toxicity with fever, anorexia, myalgias, arthralgias, fatigue, gastrointestinal upset and sleep disturbances; frank hypotension occurred. Thus it was not unexpected that specific pharmacological blockade of IL-1 activity in inflammatory diseases would be beneficial. Monotherapy blocking IL-1 activity in a broad spectrum of inflammatory syndromes results in a rapid and sustained reduction in disease severity. In common conditions such as heart failure and gout arthritis, IL-1 blockade can be effective therapy. Three IL-1blockers have been approved: the IL-1 receptor antagonist, anakinra, blocks the IL-1 receptor and therefore reduces the activity of IL-1α and IL-1β. A soluble decoy receptor, rilonacept, and a neutralizing monoclonal anti-interleukin-1β antibody, canakinumab, are also approved. A monoclonal antibody directed against the IL-1 receptor and a neutralizing anti-IL-1α are in clinical trials. By specifically blocking IL-1, we have learned a great deal about the role of this cytokine in inflammation but equally important, reducing IL-1 activity has lifted the burden of disease for many patients.

22 Review Th17 cells and IL-17 a--focus on immunopathogenesis and immunotherapeutics. 2013

van den Berg, Wim B / McInnes, Iain B. ·Rheumatology Research and Advanced Therapeutics, Department of Rheumatology, Radboud University Nijmegen Medical Center, Geert Grooteplein 26, 6525 GA Nijmegen, The Netherlands. Electronic address: w.vandenberg@reuma.umcn.nl. ·Semin Arthritis Rheum · Pubmed #24157091.

ABSTRACT: IMPORTANCE: Accumulating evidence suggests that IL-17 A has broad pathogenic roles in multiple autoimmune and immune-mediated inflammatory diseases, including psoriasis and rheumatoid arthritis (RA). The development of new therapies that inhibit IL-17 pathway signaling is of clinical significance. OBJECTIVES: This review aims to summarize the current preclinical evidence on the role of Th17 cells and IL-17 and related cytokines in immune-mediated disease pathophysiology, with a focus on psoriasis and rheumatoid arthritis, as well as to summarize recent clinical trials in these indications with newly developed IL-17 pathway inhibitors. METHODS: A systematic literature search was conducted of PubMed using relevant keywords. Studies were assessed according to recent relevance to IL-17-mediated pathophysiology and clinical IL-17 inhibition. Experimental animal models of autoimmune disease and clinical studies that focused on IL-17 pathway inhibitors were included. RESULTS: Preclinical studies suggest that IL-17A is an attractive therapeutic target. Several IL-17A inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibodies, secukinumab and ixekizumab, and the anti-17RA monoclonal antibody brodalumab. Each has shown variable and sometimes favorable results in proof-of-concept and phase II clinical trials and is currently undergoing further clinical evaluation in a range of immune-mediated diseases. CONCLUSION: Targeting the IL-17 pathway shows promise as strategy to treat immune-mediated diseases ranging from skin to joints.

23 Review GM-CSF as a therapeutic target in inflammatory diseases. 2013

van Nieuwenhuijze, Annemarie / Koenders, Marije / Roeleveld, Debbie / Sleeman, Matthew A / van den Berg, Wim / Wicks, Ian P. ·Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Rheumatology and Advanced Therapeutics, University Medical Centre Nijmegen, Nijmegen, The Netherlands; Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia. ·Mol Immunol · Pubmed #23933508.

ABSTRACT: GM-CSF is a well-known haemopoietic growth factor that is used in the clinic to correct neutropaenia, usually as a result of chemotherapy. GM-CSF also has many pro-inflammatory functions and recent data implicates GM-CSF as a key factor in Th17 driven autoimmune inflammatory conditions. In this review we summarize the findings that have led to the development of GM-CSF antagonists for the treatment of autoimmune diseases like rheumatoid arthritis (RA) and discuss some results of recent clinical trials of these agents.

24 Review The Th17 pathway as a therapeutic target in rheumatoid arthritis and other autoimmune and inflammatory disorders. 2013

Roeleveld, Debbie M / van Nieuwenhuijze, Annemarie E M / van den Berg, Wim B / Koenders, Marije I. ·Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. ·BioDrugs · Pubmed #23620106.

ABSTRACT: Production of the pro-inflammatory cytokine interleukin (IL)-17 by Th17 cells and other cells of the immune system protects the host against bacterial and fungal infections, but also promotes the development of rheumatoid arthritis (RA) and other autoimmune and inflammatory disorders. Several biologicals targeting IL-17, the IL-17 receptor, or IL-17-related pathways are being tested in clinical trials, and might ultimately lead to better treatment for patients suffering from various IL-17-mediated disorders. In this review, we provide a clear overview of current knowledge on Th17 cell regulation and the main Th17 effector cytokines in relation to IL-17-mediated conditions, as well as on recent IL-17-related drug developments. We demonstrate that targeting the Th17 pathway is a promising treatment for rheumatoid arthritis and various other autoimmune and inflammatory diseases. However, improvements in technical developments assisting in the identification of patients suffering from IL-17-driven disease are needed to enable the application of tailor-made, personalized medicine.

25 Review Pharmacogenetics of disease-modifying antirheumatic drugs in rheumatoid arthritis: towards personalized medicine. 2013

Umićević Mirkov, Maša / Coenen, Marieke J H. ·Department of Human Genetics, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. ·Pharmacogenomics · Pubmed #23438889.

ABSTRACT: Rheumatoid arthritis is a disease showing considerable heterogeneity in all its aspects, including response to therapy. The efficacy of disease-modifying antirheumatic drugs (DMARDs), with or without biological activity, has been unambiguously established. DMARDs improve the symptoms associated with the disease, and, even more importantly, are capable of stagnating the joint damage associated with the disease. Nonetheless, a considerable proportion of patients fail to achieve an adequate response and/or experience toxicity. This variability in treatment response between individuals has given rise to an extensive search for prognostic markers in order to personalize and optimize therapy in rheumatoid arthritis patients. Pharmacogenetics, the study of genetic variation underlying differential responses to drugs, is a rapidly progressing field in rheumatology that might enable personalized therapy in rheumatic diseases. This review will summarize the pharmacogenetics of commonly used synthetic and biological DMARDs.

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