In this article, the 2010 European League against Rheumatism (EULAR) recommendations for the management of rheumatoid arthritis (RA) with synthetic and biological disease-modifying antirheumatic drugs (sDMARDs and bDMARDs, respectively) have been updated. The 2013 update has been developed by an international task force, which based its decisions mostly on evidence from three systematic literature reviews (one each on sDMARDs, including glucocorticoids, bDMARDs and safety aspects of DMARD therapy); treatment strategies were also covered by the searches. The evidence presented was discussed and summarised by the experts in the course of a consensus finding and voting process. Levels of evidence and grades of recommendations were derived and levels of agreement (strengths of recommendations) were determined. Fourteen recommendations were developed (instead of 15 in 2010). Some of the 2010 recommendations were deleted, and others were amended or split. The recommendations cover general aspects, such as attainment of remission or low disease activity using a treat-to-target approach, and the need for shared decision-making between rheumatologists and patients. The more specific items relate to starting DMARD therapy using a conventional sDMARD (csDMARD) strategy in combination with glucocorticoids, followed by the addition of a bDMARD or another csDMARD strategy (after stratification by presence or absence of adverse risk factors) if the treatment target is not reached within 6 months (or improvement not seen at

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EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2016 update

Importance Rheumatoid arthritis (RA) occurs in about 5 per 1000 people and can lead to severe joint damage and disability. Significant progress has been made over the past 2 decades regarding understanding of disease pathophysiology, optimal outcome measures, and effective treatment strategies, including the recognition of the importance of diagnosing and treating RA early. Observations Early diagnosis and treatment of RA can avert or substantially slow progression of joint damage in up to 90% of patients, thereby preventing irreversible disability. The development of novel instruments to measure disease activity and identify the presence or absence of remission have facilitated new treatment strategies to arrest RA before joints are damaged irreversibly. Outcomes have been improved by recognizing the benefits of early diagnosis and early therapy with disease-modifying antirheumatic drugs (DMARDs). The treatment target is remission or a state of at least low disease activity, which should be attained within 6 months. Methotrexate is first-line therapy and should be prescribed at an optimal dose of 25 mg weekly and in combination with glucocorticoids; 40% to 50% of patients reach remission or at least low disease activity with this regimen. If this treatment fails, sequential application of targeted therapies, such as biologic agents (eg, tumor necrosis factor [TNF] inhibitors) or Janus kinase inhibitors in combination with methotrexate, have allowed up to 75% of these patients to reach the treatment target over time. New therapies have been developed in response to new pathogenetic findings. The costs of some therapies are considerable, but these costs are decreasing with the advent of biosimilar drugs (drugs essentially identical to the original biologic drugs but usually available at lower cost). Conclusions and relevance Scientific advances have improved therapies that prevent progression of irreversible joint damage in up to 90% of patients with RA. Early treatment with methotrexate plus glucocorticoids and subsequently with other DMARDs, such as inhibitors of TNF, IL-6, or Janus kinases, improves outcomes and prevents RA-related disability. A treat-to-target strategy aimed at reducing disease activity by at least 50% within 3 months and achieving remission or low disease activity within 6 months, with sequential drug treatment if needed, can prevent RA-related disability.

Diagnosis and Management of Rheumatoid Arthritis: A Review.

Therapeutic targets have been defined for axial and peripheral spondyloarthritis (SpA) in 2012, but the evidence for these recommendations was only of indirect nature. These recommendations were re-evaluated in light of new insights. Based on the results of a systematic literature review and expert opinion, a task force of rheumatologists, dermatologists, patients and a health professional developed an update of the 2012 recommendations. These underwent intensive discussions, on site voting and subsequent anonymous electronic voting on levels of agreement with each item. A set of 5 overarching principles and 11 recommendations were developed and voted on. Some items were present in the previous recommendations, while others were significantly changed or newly formulated. The 2017 task force arrived at a single set of recommendations for axial and peripheral SpA, including psoriatic arthritis (PsA). The most exhaustive discussions related to whether PsA should be assessed using unidimensional composite scores for its different domains or multidimensional scores that comprise multiple domains. This question was not resolved and constitutes an important research agenda. There was broad agreement, now better supported by data than in 2012, that remission/inactive disease and, alternatively, low/minimal disease activity are the principal targets for the treatment of PsA. As instruments to assess the patients on the path to the target, the Ankylosing Spondylitis Disease Activity Score (ASDAS) for axial SpA and the Disease Activity index for PSoriatic Arthritis (DAPSA) and Minimal Disease Activity (MDA) for PsA were recommended, although not supported by all. Shared decision-making between the clinician and the patient was seen as pivotal to the process. The task force defined the treatment target for SpA as remission or low disease activity and developed a large research agenda to further advance the field.

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Treating axial spondyloarthritis and peripheral spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by an international task force

Objectives Since the 2007 recommendations for the management of early arthritis have been presented, considerable research has been published in the field of early arthritis, mandating an update of the 2007 European League Against Rheumatism (EULAR) recommendations for management of early arthritis. Methods In accordance with the 2014 EULAR Standardised Operating Procedures, the expert committee pursued an approach that was based on evidence in the literature and on expert opinion. The committee involved 20 rheumatologists, 2 patients and 1 healthcare professional representing 12 European countries. The group defined the focus of the expert committee and target population, formulated a definition of 'management' and selected the research questions. A systematic literature research (SLR) was performed by two fellows with the help of a skilled librarian. A set of draft recommendations was proposed on the basis of the research questions and the results of the SLR. For each recommendation, the categories of evidence were identified, the strength of recommendations was derived and the level of agreement was determined through a voting process. Results The updated recommendations comprise 3 overarching principles and 12 recommendations for managing early arthritis. The selected statements involve the recognition of arthritis, referral, diagnosis, prognostication, treatment (information, education, pharmacological and non-pharmacological interventions), monitoring and strategy. Eighteen items were identified as relevant for future research. Conclusions These recommendations provide rheumatologists, general practitioners, healthcare professionals, patients and other stakeholders with an updated EULAR consensus on the entire management of early arthritis.

https://ard.bmj.com/content/annrheumdis/76/6/948.full.pdf

2016 update of the EULAR recommendations for the management of early arthritis

Objective  To determine whether a treatment strategy based on structured ultrasound assessment would lead to improved outcomes in rheumatoid arthritis, compared with a conventional strategy. Design  Multicentre, open label, two arm, parallel group, randomised controlled strategy trial. Setting  Ten rheumatology departments and one specialist centre in Norway, from September 2010 to September 2015. Participants  238 patients were recruited between September 2010 and April 2013, of which 230 (141 (61%) female) received the allocated intervention and were analysed for the primary outcome. The main inclusion criteria were age 18-75 years, fulfilment of the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis, disease modifying anti-rheumatic drug naivety with indication for disease modifying drug therapy, and time from first patient reported swollen joint less than two years. Patients with abnormal kidney or liver function or major comorbidities were excluded. Interventions  122 patients were randomised to an ultrasound tight control strategy targeting clinical and imaging remission, and 116 patients were randomised to a conventional tight control strategy targeting clinical remission. Patients in both arms were treated according to the same disease modifying anti-rheumatic drug escalation strategy, with 13 visits over two years. Main outcome measures  The primary endpoint was the proportion of patients with a combination between 16 and 24 months of clinical remission, no swollen joints, and non-progression of radiographic joint damage. Secondary outcomes included measures of disease activity, radiographic progression, functioning, quality of life, and adverse events. All participants who attended at least one follow-up visit were included in the full analysis set. Results  26 (22%) of the 118 analysed patients in the ultrasound tight control arm and 21 (19%) of the 112 analysed patients in the clinical tight control arm reached the primary endpoint (mean difference 3.3%, 95% confidence interval −7.1% to 13.7%). Secondary endpoints (disease activity, physical function, and joint damage) were similar between the two groups. Six (5%) patients in the ultrasound tight control arm and seven (6%) patients in the conventional arm had serious adverse events. Conclusions  The systematic use of ultrasound in the follow-up of patients with early rheumatoid arthritis treated according to current recommendations is not justified on the basis of the ARCTIC results. The findings highlight the need for randomised trials assessing the clinical application of medical technology. Trial registration  Clinical trials NCT01205854.

https://www.bmj.com/content/bmj/354/bmj.i4205.full.pdf

Ultrasound in management of rheumatoid arthritis: ARCTIC randomised controlled strategy trial

Objective To investigate whether an intensive early rheumatoid arthritis (RA) treat-to-target (T2T) strategy could be improved through the use of musculoskeletal ultrasound (MSUS) assessment of disease activity. Methods 111 newly diagnosed patients with RA or undifferentiated arthritis (symptom duration Results Groups were matched for baseline clinical, demographic and radiographic features. The intervention group received more intensive DMARD therapy. Both groups demonstrated significant improvements in DAS44 (mean change: control −2.58, intervention −2.69; 95% CI difference between groups −0.70 to 0.48; p=0.72). There were no significant between-group differences for any ACR core-set variables, except DAS44 remission after 18 months (control 43%, intervention 66%; p=0.03). There was minimal progression of MRI and radiographic erosions and no difference in imaging outcomes or serious adverse event rates. Conclusions In early RA, a MSUS-driven T2T strategy led to more intensive treatment, but was not associated with significantly better clinical or imaging outcomes than a DAS28-driven strategy. Trial registration number NCT00920478.

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Jonathan Foley

Papers

Targeting ultrasound remission in early rheumatoid arthritis: the results of the TaSER study, a randomised clinical trial