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’.

/pdf/2010-rheumatoid-arthritis-classification-criteria-an-h6w7bcnbf6.pdf

2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

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’.

https://ard.bmj.com/content/annrheumdis/69/9/1580.full.pdf

2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

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

/pdf/eular-recommendations-for-the-management-of-rheumatoid-4fujp4paik.pdf

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

The increased understanding of the immune mechanisms of rheumatoid arthritis has led to the development of a considerable number of new therapeutic agents that alter the natural history of the disease and reduce mortality.

/pdf/the-pathogenesis-of-rheumatoid-arthritis-5ec7s76zig.pdf

The pathogenesis of rheumatoid arthritis.

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-à-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.

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

Patient-derived functional measures such as the Health Assessment Questionnaire (HAQ) are important tools in the assessment of general health, function, and disability in patients with rheumatic diseases, such as rheumatoid arthritis. In this Viewpoint, Dr Aletaha and Dr Smolen discuss the use of these measures and their derivatives in predicting outcome in patients with rheumatic disease.

The health assessment questionnaire in routine clinical practice.

https://ard.bmj.com/content/annrheumdis/81/6/747.full.pdf

Reflections on a contemporary European tragedy

We have read with great interest the article by Redeker et al 1 investigating the determinants of psychological well-being in axial spondyloarthritis (SpA). The authors observed that among 1736 patients aged 18–79 years, 68% of subjects displayed depressive symptoms, ranging from mild to severe according to the five-item WHO Well-Being Index. This article clearly points out the burden of depressive symptoms in patients with SpA and its correlation with disease activity, functional impairment and other parameters including younger age. The authors emphasise that a potential explanation for the negative association between depressive symptoms and age might be a better capability to cope with the disease of adult compared with young patients. This aspect prompted our reflections, as the psychological impact of rheumatic and musculoskeletal diseases (RMDs) in young people is a major unmet need.

We previously reported that over 90% of young patients with RMDs outline an impact of their condition on mental health which, …

https://ard.bmj.com/content/annrheumdis/78/6/e54.full.pdf

Missing pebble in the mosaic of rheumatic diseases and mental health: younger does not always mean happier.

Background Hepcidin is an important link between inflammation and anemia in patients with rheumatoid arthritis (RA); hemoglobin itself is considered a negative acute phase measure in chronic inflammatory conditions like RA. However, the longitudinal association of hepcidin and hemoglobin with RA disease activity and acute phase remains to be explored. Objectives We aimed to explore these associations in patients with RA. Methods We consecutively included RA outpatients in a routine academic setting. Each patient was evaluated at baseline and 12 weeks thereafter using the clinical disease activity index (CDAI) and extensive peripheral blood tests, including serology, acute phase response (erythrocyte sedimentation rate, ESR; C reactive protein, CRP; and fibrinogen) and measures of iron metabolism (ferritin; transferrin; transferrin saturation, TS; hepcidin; and peripheral erythroid burst forming units, BFU-E). We analyzed baseline and week 12 values cross-sectionally in all patients; and change scores from baseline to week 12 in a subset of active patients with CDAI≥10 and a new DMARD initiation at baseline. We performed principal component analysis (PCA) to identify themes for all included variables. The strength of association of hepcidin and hemoglobin with the identified themes from the PCA was then analyzed. Results Eighty-eight patients (68 females, 77%) were included (mean±SD age: 58±12 years; disease duration: 9.3±9.6 years). PCA identified four themes for all included parameters: clinical activity, acute phase, iron metabolism and hematopoiesis. At baseline and week 12 (steady state), both hepcidin and hemoglobin levels were ascribable primarily to the theme “iron metabolism”. Hemoglobin was also ascribable to “clinical activity” – to a similar extent as other acute phase parameters; but even more to the theme “acute phase”. Conversely, 12-week changes in hepcidin levels were ascribable to “changes in acute phase”, while changes in hemoglobin levels were ascribable to “changes in clinical activity” (Figure). In multivariable analysis CDAI changes were negatively, and BFU-E changes were positively, associated with hemoglobin changes (R 2 =0.615, p Figure: Loadings of hepcidin (solid lines) and hemoglobin (dotted lines) to the themes identified by principal component analysis, for baseline values (left), and for changes between baseline and week 12 (right) Conclusions In patients with RA, changes in hepcidin levels reflect changes in acute phase response, but not changes in clinical disease activity; changes in hemoglobin levels occur in conjunction with changes in clinical disease activity, but not with changes of the acute phase response. The association of clinical disease activity with hemoglobin seems to be stronger than its association with other acute phase parameters. References Song SN et al. Arthritis Res Ther. 2013;15:R141. Disclosure of Interest None declared

FRI0133 Understanding Anemia in Rheumatoid Arthritis: The Association of Hemoglobin and Hepcidin Levels with Clinical Disease Activity and Acute Phase Response

We would like to thank Dr Pethoe-Schramm and colleagues for their comment on our paper1 and the diligent assessment of the data we presented.2 The authors addressed each of our Figures sequentially and, therefore, it will be a pleasure to respond here accordingly.

Before doing so, we would like to mention that in contrast to other studies, like the one by Wang et al 3 which we also referred to in our paper, we approached the analyses by using Clinical Disease Activity Index (CDAI) remission criteria (endorsed by ACR-EULAR for this purpose) rather than "remission" criteria by the Disease Activity Score using 28 joint counts (DAS28) .4 5 As often described, DAS28 <2.6 is an inappropriate remission endpoint because many patients still have residual swollen joints which are drivers of joint damage.6 7 Moreover, acute phase reactants are highly weighted in the formula.8 9 Consequently, DAS28 remission rates are exaggerated and misleading in the context of interleukin-6 (IL-6) inhibition by cytokine receptor inhibitors like tocilizumab or pathway inhibitors like Janus kinase inhibitors;10 11 moreover, these issues cannot be overcome by lowering the threshold for the remission cutpoint.5 12 Finally, since DAS28 includes an acute phase reactant, using it as an outcome to evaluate the role of C-reactive protein (CRP) cannot be seen as independent of CRP and, therefore, may be circular.

Equally importantly, we did not start by asking the question of the ‘distribution of baseline… concentrations of…CRP’ in relation to achieving DAS28 <2.6 or not, but rather asked the question, which CRP-levels those patients who achieved stringent remission at endpoint had at baseline and compared this with baseline CRP levels in patients who had other disease activity states at endpoint and not just non-remission. Thus, …

https://ard.bmj.com/content/annrheumdis/early/2020/07/31/annrheumdis-2020-218403.full.pdf

Response to: 'Comment on 'Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab'' by Pethoe-Schramm et al.

Daniel Aletaha

Papers

The health assessment questionnaire in routine clinical practice.

Reflections on a contemporary European tragedy

Missing pebble in the mosaic of rheumatic diseases and mental health: younger does not always mean happier.

FRI0133 Understanding Anemia in Rheumatoid Arthritis: The Association of Hemoglobin and Hepcidin Levels with Clinical Disease Activity and Acute Phase Response

Response to: 'Comment on 'Implication of baseline levels and early changes of C-reactive protein for subsequent clinical outcomes of patients with rheumatoid arthritis treated with tocilizumab'' by Pethoe-Schramm et al.