Methods used to assess remission and low disease activity in rheumatoid arthritis
Introduction
The progressive clarification in the pathogenesis of Rheumatoid arthritis (RA) and the subsequent biopharmaceutical discoveries, led to the establishment of more effective medications [1], [2], [3]. Indeed, successful long term use of biological agents require ongoing monitoring to avoid drug toxicity [4], [5], [6], [7]. However, since biologic response modifiers have been proved to markedly reduce signs and symptoms of the disease, better outcomes are expected, and reported. Thus, remission has become the goal of RA therapy [8].
Key point to an optimal treatment success in RA is an aggressive treatment approach to the disease [9]. Patients should be assessed at least once every 3 months, and activity should be evaluated using the proposed indices [10]. Standardized measures allow an evaluation of the disease over time with the possibility of designing a progress chart, therefore highlighting effects of treatment.
The impressive achievements in controlling RA have needed parallel development of the methods suitable to assess the results of the new medications. Adequate instruments to define remission in RA have been proposed on the basis of patients' follow-up both in trials and in clinical practice and then validated [11], [12]. To date recommendations are the result of collaborative efforts between the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Proposed definitions for remission include clinical criteria as defined by ACR and EULAR indices and additionally radiographic arrest [13].
However, reports on results of clinical trials show a heterogeneous use of response and remission criteria. To interpret the value of the claims made in support of the efficacy of a treatment it is important to understand the significance of the different criteria for remission.
This review aims to describe the criteria for RA remission used in clinical practice and to discuss their advantages and limitations.
Section snippets
Efforts to define remission and reliability of present criteria
The evaluation of the activity of RA is often difficult and may lead to misinterpretation if not all the components of the disease are considered. Multiple indices that combine set of values are required and they result to be more informative than single variables alone [14], [15]. Many scales have been proposed for assessing the patients’ clinical status, which were addressed to the different domains of the disease: inflammatory activity, physical function and organ damage.
The most reliable
Low disease activity state (LDAS) or minimal disease activity (MDA)
As reaching and maintaining a low disease activity proved more useful than reaching important improvement from high levels of disease activity, the concept of minimal disease activity was developed, and in 2005 OMERACT proposed a definition of low disease activity state (LDAS) or minimal disease activity (MDA). LDAS corresponds to “that state of disease activity deemed a useful target of treatment by both the patient and the physician, given current treatment possibilities and limitations” [36]
Conclusions
At present, reports on results of clinical trials for RA show a heterogeneous use of both EULAR and ACR criteria.
DAS showed to fare better in clinical function as it is a continuous index. DAS28 requires a lower number of joints to be counted, and seems to be better suited for use in clinical practice but could lead to underestimating the disease. SDAI and CDAI are simplified indices derived from DAS and their criteria for remission appear to be more stringent and more specific, allowing only a
Take-home messages
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Remission is regarded as the goal of rheumatoid arthritis therapy.
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Disease Activity Score 44-joint count (DAS 44) showed to fare better in clinical function.
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Disease Activity Score 28-joint count (DAS28) seems to be more suitable for use in clinical practice.
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Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI) criteria appear to be more stringent and more specific than other criteria.
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To date only FDA criteria consider radiographic arrest, assessed by
Acknowledgement
This study was in part supported by the Italian Medicines Agency (AIFA) within the independent drug research program, contract no. FARM5KJ9P5.
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2018, Seminars in Arthritis and RheumatismCitation Excerpt :With DAS28 definition, the weighted parts of tender and swollen joint counts in the formula deriving the final activity score allow a theoretically high number of residual abnormal joints (i.e., either tender or swollen at physical examination), provided that other components of the composite score are sufficiently low to result in a globally low score. The low stringency of the DAS28 remission criteria, especially in relation to residual joint counts, has already been addressed in previous studies [48,49] and is also apparent from the difference between the proportions of patients with a single visit in remission and that of patients in sustained remission [50]. Moreover, the DAS28 seemed to be less stringent with respect to elevation of the global assessments of activity and pain comparing with the SDAI.
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2015, Revue du Rhumatisme (Edition Francaise)Prevalence and concordance of early and sustained remission assessed by various validated indices in the early arthritis "ESPOIR" cohort
2014, Joint Bone SpineCitation Excerpt :It should however be emphasised here that this theoretic situation is actually very unlikely in clinical practice, since combining such a high number of inflammatory joints with a health state considered as very satisfactory (extremely low disease activity by the patient self assessment) and normal acute phase reactants values is a very outlying, if not impossible, situation. The low stringency of the DAS28 remission criteria, especially in relation to residual joint counts, has already been addressed in previous studies [22,23] and is also apparent from the difference between the proportions of patients with a single visit in remission and that of patients in sustained remission [24]. We showed that the higher the baseline disease activity (as assessed by DAS28), the more limited the chance to achieve remission, with a consistent association whatever the definition of remission was chosen.
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2011, Autoimmunity ReviewsCitation Excerpt :RA is a systemic autoimmune disease in which a Th1 response based on proinflammatory cytokines leads to joint inflammation and injury [189] in as much as 1% of the general population [39]. Over the past year there have been significant contributions to the clinical management via biomarkers [190] and imaging techniques [191] for bone erosions and comprehensive disease activity scoring [192] and prediction [193]. One fascinating hypothesis was supported by experimental data and is based on the possibility that the modulation of the commensal microbiota may provide changes in disease activity and actively induce tolerant responses [194], as well represented in celiac disease [195,196].