Showing papers by "Daniel Aletaha published in 2010"
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Humboldt University of Berlin6, University of Toronto7, National Jewish Health8, Brigham and Women's Hospital9, Paris Descartes University10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University Health Centre20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25, University of Kansas26, Women's College Hospital27
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classifi cation criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classifi cation criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated infl ammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/ or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classifi cation as ‘defi nite RA’ is based on the confi rmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classifi cation system redefi nes the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defi ning the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
7,120 citations
Medical University of Vienna1, Boston University2, Arthritis Research UK3, Johns Hopkins University4, University of California, San Francisco5, Charité6, University of Toronto7, National Jewish Health8, Harvard University9, University of Paris10, University of Leeds11, Catholic University of the Sacred Heart12, Erasmus University Rotterdam13, University of Colorado Denver14, Leiden University15, University of California, San Diego16, University of Massachusetts Medical School17, University of Michigan18, University of Washington19, McGill University20, University of Pittsburgh21, Ministry of Health (New Zealand)22, New York University23, University of Manchester24, University of Amsterdam25
TL;DR: This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features.
Abstract: Objective The 1987 American College of Rheumatology (ACR; formerly the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticised for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. Methods A joint working group from the ACR and the European League Against Rheumatism developed, in three phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease—this being the appropriate current paradigm underlying the disease construct ‘RA’. Results In the new criteria set, classification as ‘definite RA’ is based on the confirmed presence of synovitis in at least one joint, absence of an alternative diagnosis better explaining the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in four domains: number and site of involved joints (range 0–5), serological abnormality (range 0–3), elevated acute-phase response (range 0–1) and symptom duration (two levels; range 0–1). Conclusion This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimise the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct ‘RA’.
5,964 citations
Utrecht University1, Leiden University2, University of Crete3, Humboldt University of Berlin4, University of Genoa5, University of Paris6, University of Leeds7, Hospital for Special Surgery8, University of Santiago de Compostela9, University of Erlangen-Nuremberg10, University of Toronto11, University of Glasgow12, Autonomous University of Madrid13
TL;DR: The 10 recommendations are supposed to inform patients, rheumatologists and other stakeholders about strategies to reach optimal outcomes of RA based on evidence and expert opinion.
Abstract: Aiming at therapeutic targets has reduced the risk of organ failure in many diseases such as diabetes or hypertension. Such targets have not been defined for rheumatoid arthritis (RA).
1,676 citations
Medical University of Vienna1, Maastricht University2, Leiden University3, Paris Descartes University4, University of Leeds5, Pierre-and-Marie-Curie University6, Utrecht University7, Humboldt State University8, University of Montpellier9, University of Genoa10, University of Santiago, Chile11, Autonomous University of Madrid12, University of Glasgow13, Charles University in Prague14, Radboud University Nijmegen15, King's College London16, Sapienza University of Rome17, Karolinska Institutet18, Oregon Health & Science University19, Tufts University20, Charité21
TL;DR: In this article, the authors present a set of recommendations for the treatment of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects.
Abstract: Treatment of rheumatoid arthritis (RA) may differ among rheumatologists and currently, clear and consensual international recommendations on RA treatment are not available. In this paper recommendations for the treatment of RA with synthetic and biological disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs) that also account for strategic algorithms and deal with economic aspects, are described. The recommendations are based on evidence from five systematic literature reviews (SLRs) performed for synthetic DMARDs, biological DMARDs, GCs, treatment strategies and economic issues. The SLR-derived evidence was discussed and summarised as an expert opinion in the course of a Delphi-like process. Levels of evidence, strength of recommendations and levels of agreement were derived. Fifteen recommendations were developed covering an area from general aspects such as remission/low disease activity as treatment aim via the preference for methotrexate monotherapy with or without GCs vis-a-vis combination of synthetic DMARDs to the use of biological agents mainly in patients for whom synthetic DMARDs and tumour necrosis factor inhibitors had failed. Cost effectiveness of the treatments was additionally examined. These recommendations are intended to inform rheumatologists, patients and other stakeholders about a European consensus on the management of RA with DMARDs and GCs as well as strategies to reach optimal outcomes of RA, based on evidence and expert opinion.
1,372 citations
TL;DR: The evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care is expanded, allowing concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care.
Abstract: Objective A systematic literature review (SLR; 2009–2014) to compare a target-oriented approach with routine management in the treatment of rheumatoid arthritis (RA) to allow an update of the treat-to-target recommendations.
Methods Two SLRs focused on clinical trials employing a treatment approach targeting a specific clinical outcome were performed. In addition to testing clinical, functional and/or structural changes as endpoints, comorbidities, cardiovascular risk, work productivity and education as well as patient self-assessment were investigated. The searches covered MEDLINE, EMBASE, Cochrane databases and Clinicaltrial.gov for the period between 2009 and 2012 and separately for the period of 2012 to May of 2014.
Results Of 8442 citations retrieved in the two SLRs, 176 articles underwent full-text review. According to predefined inclusion/exclusion criteria, six articles were included of which five showed superiority of a targeted treatment approach aiming at least at low-disease activity versus routine care; in addition, publications providing supportive evidence were also incorporated that aside from expanding the evidence provided by the above six publications allowed concluding that a target-oriented approach leads to less comorbidities and cardiovascular risk and better work productivity than conventional care.
Conclusions The current study expands the evidence that targeting low-disease activity or remission in the management of RA conveys better outcomes than routine care.
397 citations
Boston University1, Medical University of Vienna2, Arthritis Research UK3, Ministry of Health (New Zealand)4, University of Pittsburgh5, Johns Hopkins University6, University of California, San Francisco7, Charité8, University of Toronto9, National Jewish Health10, University of Montpellier11, Harvard University12, Paris Descartes University13, University of Leeds14, Catholic University of the Sacred Heart15, Erasmus University Rotterdam16, University of Colorado Denver17, Leiden University18, University of California, San Diego19, University of Massachusetts Medical School20, University of California, Los Angeles21, University of Michigan22, University of Washington23, McGill University24, University of North Carolina at Chapel Hill25, New York University26, Seattle Children's27, University of Manchester28, University of Amsterdam29, University of Kansas30
TL;DR: The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis.
Abstract: Objective. The American College of Rheumatology and the European League Against Rheumatism have developed new classification criteria for rheumatoid arthritis (RA). The aim of Phase 2 of the development process was to achieve expert consensus on the clinical and laboratory variables that should contribute to the final criteria set. Methods. Twenty-four expert RA clinicians (12 from Europe and 12 from North America) participated in Phase 2. A consensus-based decision analysis approach was used to identify factors (and their relative weights) that influence the probability of "developing RA," complemented by data from the Phase 1 study. Patient case scenarios were used to identify and reach consensus on factors important in determining the probability of RA development. Decision analytic software was used to derive the relative weights for each of the factors and their categories, using choice-based conjoint analysis. Results. The expert panel agreed that the new classification criteria should be applied to individuals with undifferentiated inflammatory arthritis in whom at least 1 joint is deemed by an expert assessor to be swollen, indicating definite synovitis. In this clinical setting, they identified 4 additional criteria as being important: number of joints involved and site of involvement, serologic abnormality, acute-phase response, and duration of symptoms in the involved joints. These criteria were consistent with those identified in the Phase 1 data-driven approach. Conclusion. The consensus-based, decision analysis approach used in Phase 2 complemented the Phase 1 efforts. The 4 criteria and their relative weights form the basis of the final criteria set.
316 citations
TL;DR: A systematic literature search including all clinical trials testing clinical, functional, or structural values of a targeted treatment approach for rheumatoid arthritis showed significantly better clinical outcomes of targeted approaches than routine approaches.
Abstract: Objectives
To summarise existing evidence on a target oriented approach for rheumatoid arthritis (RA) treatment.
263 citations
TL;DR: Evidence is provided of the utility and validity of the DAREA for PsA disease activity assessment and a second name should be assigned to this score: DAPSA (for ‘Disease Activity index for PSoriatic Arthritis’).
Abstract: Background and objectives Instruments for measuring disease activity in psoriatic arthritis (PsA) are not yet firmly established, and most of the currently employed ones have been derived for rheumatoid arthritis. Some of these instruments are based on 28 joint counts, which do not capture joints frequently affected in PsA. Therefore, the reliability and validity of DAREA (for ‘Disease Activity index for REactive Arthritis’), which was originally developed for reactive arthritis and employs a 66/68 joint count, was tested in patients with PsA. Methods Trial data from the Infliximab Multinational Psoriatic Arthritis Controlled Trial were analysed. Results were then independently validated using an observational data set. DAREA was compared to other composite indices regarding correlations with core set variables, sensitivity to change and criterion validity. Results Good correlation of the DAREA with single items of disease activity, other composite scores (r=0.6−0.9) and physical function (Health Assessment Questionnaire; r=0.5) was found. Likewise, DAREA was at least as sensitive to change as the other indices and more so in patients with distal interphalangeal joint involvement. Additionally, DAREA correlated well with radiographic changes. Conclusion The analyses of this study provide evidence of the utility and validity of the DAREA for PsA disease activity assessment. A second name should therefore be assigned to this score: DAPSA (for ‘Disease Activity index for PSoriatic Arthritis’).
251 citations
TL;DR: A data-driven approach to investigate, in patients newly presenting with undifferentiated inflammatory synovitis, key variables that discriminate the subset of patients at sufficiently high risk of persistent or erosive disease for the purpose of developing new criteria for rheumatoid arthritis (RA).
Abstract: Objective To apply a data-driven approach to investigate, in patients newly presenting with undifferentiated inflammatory synovitis, key variables that discriminate the subset of patients at sufficiently high risk of persistent or erosive disease for the purpose of developing new criteria for rheumatoid arthritis (RA). Methods In this first phase of the collaborative effort of the American College of Rheumatology and European League Against Rheumatism to develop new criteria for RA, a pooled analysis of early arthritis cohorts made available by the respective investigators is presented. All the variables associated with the gold standard of treatment with methotrexate during the first year after enrolment were first identified. Principal component analysis was then used to identify among the significant variables those sets that represent similar domains. In a final step, from each domain one representative variable was extracted, all of which were then tested for their independent effects in a multivariate regression model. From the OR in that final model, the relative weight of each variable was estimated. Results The final domains and variables identified by this process (and their relative weights) were: swelling of a metacarpophalangeal joint (MCP; 1.5), swelling of a proximal interphalangeal joint (PIP; 1.5), swelling of the wrist (1.5), tenderness of the hand (ie, MCP, PIP or wrist (2)), acute phase reaction (ie, C reactive protein or erythrocyte sedimentation rate and weights for moderate or high elevations of either one (1 for moderate, 2 for high elevation)) and serological abnormalities (ie, rheumatoid factors or anti-citrullinated protein antibodies, again with separate weights for moderate or high elevations (2 and 4, respectively)). Conclusion The results of this first phase were subsequently used in the second phase of the project, which is reported in a separate methodological paper, and for derivation of the final set of criteria.
175 citations
TL;DR: The costly sequelae of insufficiently controlled RA justify intensive escalations of treatment in this disease, and effective control of disease activity seems to be a prudent use of societal resources.
Abstract: Objective To review the cost effectiveness of rheumatoid arthritis (RA) treatments and inform the clinical recommendations by the European League Against Rheumatism. Methods A systematic literature search and review of the health economic evidence on RA treatment options was performed. Results Despite diverse methodological approaches, health economic analyses are concordant: at onset of disease, traditional disease-modifying antirheumatic drugs (DMARDs) are cost effective—that is, treatment merits outweigh treatment costs. If DMARDs fail, therapeutic escalation with tumour necrosis factor α inhibitors (TNFi) is cost effective when standard dosing schemes are employed. If TNFi fail, rituximab or abatacept is cost effective. Economic evidence for switching TNFi remains sparse. Conclusions The costly sequelae of insufficiently controlled RA justify intensive escalations of treatment in this disease. By maintaining function, patients are kept in the work process, reducing indirect costs. Quality of life is improved at an expense commonly accepted for chronic diseases. Effective control of disease activity seems to be a prudent use of societal resources.
155 citations
TL;DR: Proof in favour of any steering method is lacking and the best medication sequence is still not known, but intensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment.
Abstract: Objectives To perform a systematic literature review of effective strategies for the treatment of rheumatoid arthritis (RA). Methods As part of a European League Against Rheumatism (EULAR) Task Force investigation, a literature search was carried out from January 1962 until February 2009 in PubMed/Ovid Embase/Cochrane and EULAR/American College of Rheumatism (ACR)) abstracts (2007/2008) for studies with a treatment strategy adjusted to target a predefined outcome. Articles were systematically reviewed and clinical outcome, physical function and structural damage were compared between intensive and less intensive strategies. The results were evaluated by an expert panel to consolidate evidence on treatment strategies in RA. Results The search identified two different kinds of treatment strategies: strategies in which the reason for treatment adjustment differed between the study arms (‘steering strategies’, n=13) and strategies in which all trial arms used the same clinical outcome to adjust treatment with different pharmacological treatments (‘medication strategies’, n=7). Both intensive steering strategies and intensive medication strategies resulted in better outcome than less intensive strategies in patients with early active RA. Conclusion Intensive steering strategies and intensive medication strategies produce a better clinical outcome, improved physical function and less structural damage than conventional steering or treatment. Proof in favour of any steering method is lacking and the best medication sequence is still not known.
TL;DR: Physical disability becomes worse with increasing levels of comorbidity, irrespective of disease activity, in patients with established RA.
Abstract: Background Physical disability is a main outcome in rheumatoid arthritis (RA) which tends to increase with comorbidities. However, the extent to which comorbidities contribute to the multifactorial process of disability has not been investigated. Objective To quantify the contribution of comorbidity to physical disability in patients with RA. Methods In a prospective cohort study, age-adjusted Charlson comorbidity index (CCI A ), serial measurements of disease activity and functional disability (evaluated by the Health Assessment Questionnaire Disability Index, HAQ) of 380 patients with established RA seen at an outpatient clinic over 1 year (June 2007 to July 2008) were ascertained. The association between comorbidity and physical disability was assessed using analysis of variance (ANOVA) and adjusted general linear regression models. Results Four patient groups with increasing levels of comorbidity (CCI A 0, 1–2, 3–4 and 5–9; potential range 0–38) were defined. Mean HAQ scores were significantly different across these groups (0.67, 0.80, 1.24, 1.40, respectively; p A on disability were similar within different strata of disease activity: namely, remission (0.26, 0.31, 0.48 and 0.88, p Conclusion Physical disability becomes worse with increasing levels of comorbidity, irrespective of disease activity.
TL;DR: An approach to estimate the numerical relationship between HAQ and damage as 0.01 HAQ points/TSS unit is presented, although the linear relationship may not be generally valid.
Abstract: Background Joint damage is an important outcome in trials of rheumatoid arthritis (RA), usually assessed by Total Sharp Score (TSS). It is currently unknown how it translates numerically into disability by the Health Assessment Questionnaire (HAQ). Objective To determine the units of HAQ score corresponding to one TSS unit. Methods A short-term observational trial of glucocorticoids in RA (the ‘BEst LIfe with Rheumatoid Arthritis’ (BELIRA) trial) was evaluated, using randomised controlled clinical trial (RCT) data for confirmation. For each trial arm HAQ, TSS and the Simplified Disease Activity Index (SDAI) were assessed. Based on the hypothesis that short-term HAQ changes will mostly be due to changes of disease activity, activity HAQ (ACT-HAQ) at end point (EP) was determined and remaining disability defined as damage related (DAM-HAQ). Using TSS at EP, the HAQ units corresponding to a TSS unit were estimated. Results In BELIRA, one TSS unit corresponded to a mean of 0.017 HAQ units; to account for other causes of irreversible disability, the 25th percentile was used: 0.011 HAQ units/TSS unit. In RCT trial arms, the HAQ/TSS were similar (0.013 and 0.015 in established and early RA, respectively; 25th percentile: 0.010). The correlation between DAM-HAQ EP and TSS was r=0.829. Over 5 years, damage would amount to an increase of irreversible HAQ of 0.33 on placebo, 0.13 on disease-modifying antirheumatic drugs (DMARDs) and 0.03 on TNF inhibitors+methotrexate (MTX). Conclusion An approach to estimate the numerical relationship between HAQ and damage as 0.01 HAQ points/TSS unit is presented, although the linear relationship may not be generally valid. This allows the assessment of functional correlates of radiographic changes in trials.
TL;DR: Among the currently available indices used in arthritic conditions, the DAREA best reflects the domains found to be important in PsA.
Abstract: Objective Specific composite indices assessing disease activity in psoriatic arthritis (PsA) have not yet been sufficiently validated. The objective of this study was to identify instruments best reflecting disease activity in PsA. Methods Measures for inclusion in clinical trials, as recommended by the OMERACT-7/8 PsA workshops, were assessed. A principal component analysis (PCA) was performed with cross-sectional data of 105 patients with PsA to identify a minimal set of important dimensions for a disease activity assessment tool for PsA. This was compared with components contained in existing composite indices. Results The PCA revealed four principal components best reflecting disease activity. The first contained patient global and pain assessment; the second contained 66/68 swollen and tender joint counts as main variables; C-reactive protein (CRP) best loaded to the third component; and the fourth was loaded by skin assessment but did not reach significance. When comparing the three significant principal components with items of established composite measures, they were best covered by the Disease Activity Index for Reactive Arthritis (DAREA) which comprises patient pain and global assessments, 66/68 joint counts and CRP. Conclusion Among the currently available indices used in arthritic conditions, the DAREA best reflects the domains found to be important in PsA.
Journal Article•
TL;DR: The accurate assessment of disease is an important part of the care of patients with RA, and new and simplified measures have evolved to allow physicians to evaluate the indication and effect of particular therapies.
Abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by progressive damage of diathrodial joints, with variable extra-articular manifestations. Joint damage begins early in the course of the disease as a consequence of the active inflammation, and can lead to progressive and irreversible disability. Successful treatment relies on patients attaining low disease activity or a state of remission, which have become achievable goals since the improved use of methotrexate (MTX) and the introduction of biological agents, especially tumor necrosis factor (TNF) inhibitors. To allow physicians to evaluate the indication and effect of particular therapies, accurate assessment of disease activity is necessary. Disease states in RA can be evaluated by a number of measures. These include signs and symptoms, such as counts of tender and swollen joints; laboratory measures like the acute phase response, which is a direct reflection of the underlying inflammatory activity; and patient-focused variables to measure pain and global assessment of disease activity. Some of these (and additional) measures are used in composite indices to assess disease activity or a disease activity state at any point in time and can inform the physician (and patient) about improvement (or deterioration) in disease activity from or states at a particular level at baseline, to that seen at any specific time point. The accurate assessment of disease is, therefore, an important part of the care of patients with RA. However, it can be complex to perform in the clinical setting, so new and simplified measures have evolved. Next to disease activity, the disease outcome is of utmost importance, in particular disability and quality of life, which are assessed using patient reported questionnaires. Radiographic assessment of structural changes is also an important outcome of RA and mirrors joint damage. The latest developments in the field are discussed and will help to identify patients who can benefit most from today's opportunities of pharmacotherapy, allowing optimization of patient care.
TL;DR: These results suggest the acceptance of ambitious treatment concepts in practice, and reflect widespread adoption of desirable standards of care, in practice.
Abstract: Background Therapeutic approaches to rheumatoid arthritis (RA) have undergone significant changes. The importance of tight control and early treatment, rapidly altered if goals are not achieved, is supported by evidence. However, it is unknown to what extent these insights are accepted by practitioners in clinical practice. Objective To obtain information about standard follow-up and treatment practices, and rheumatologists9 aims in the care of patients with RA. Methods A survey conducted at the 2008 EULAR Congress. Results Most specialists, who were mainly from Europe and Latin America, were well-informed about recent concepts: two-thirds specified remission as a major goal. The experts attempted to reach treatment aims within 12–14 weeks, altering treatment otherwise. Disease activity assessment by composite measures is performed by a majority, although one-third preferentially relied upon their judgment. Conclusion These results suggest the acceptance of ambitious treatment concepts in practice. Although voluntary surveys have limitations, the answers reflect widespread adoption of desirable standards of care.
TL;DR: A new approach to the assessment of physical function uses computerised adaptive testing, by which precision and reliability of the measurement can be achieved for most patients, while even requiring less time for the assessment.
Abstract: Evaluation of patient reported outcomes, and in particular physical function, have gained increasing importance in research and therapy of patients with rheumatic diseases. Most instruments that are used for that purpose are rigid and suffer from floor and ceiling effects when used in patients whose physical function differs from the average. A new approach to the assessment of physical function uses computerised adaptive testing, by which precision and reliability of the measurement can be achieved for most patients, while even requiring less time for the assessment. Well calibrated and tested item and large item data banks are a prerequisite for this purpose, a process that is summarised in the present report by Bruce and colleagues.
TL;DR: A multicenter study conducted in Japan has explored whether stopping treatment with a tumor necrosis factor inhibitor is a viable option once a state of low disease activity has been attained.
Abstract: Tapering or even discontinuation of drug therapy for rheumatoid arthritis is a desirable goal, given patient preferences in addition to safety and financial concerns, but the implications of this approach are far from clear. A multicenter study conducted in Japan has explored whether stopping treatment with a tumor necrosis factor inhibitor is a viable option once a state of low disease activity has been attained.