Composite indices to assess disease activity in rheumatoid arthritis: need of the hour

Abstract

For most rheumatic diseases, there is no single quantitative measure that can be used as “gold standard” for either diagnosis or for disease monitoring. Rheumatoid arthritis (RA) is an apt example. In absence of a single measure like elevated level of glucose for diabetes or blood pressure level in hypertension, there exist an array of disease-specific quantitative measures for RA. These measures encompass the areas of disease activity, radiological damage and functional status of the patients.1 Composite indices have been developed from these quantitative measures that describe the patient status in numerical terms useful for clinical research and patient care. However, most of them remain research tools, and are not applied to assess and monitor patient status in standard clinical care. A composite index integrates several single measures into one summary number (e.g. ‘DAS’ score, which can range from 0 to 10). Measures to assess disease activity in RA fall into two distinct groups. ‘Status measures’ assess disease activity at a specific point in time, and ‘response measures’ assess how disease activity changes over time (for example, response to medication). Composite indices such as the Disease Activity Score (DAS), DAS28, DAS28-CRP (DAS28 using C-reactive protein instead of ESR), Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) are examples of status measures. These indices are important in evaluating treatment strategies in individual RA patients. Response measures evaluate change in clinical status over time in clinical trials to determine efficacy but can also be implemented in longitudinal observational studies to evaluate clinical change over time. Two types of response measures in current usage are the American College of Rheumatology 20%, 50%, and 70% improvement (ACR 20/50/70) criteria and the European League of Associations for Rheumatology (EULAR) improvement criteria. They are not designed for the clinical management of individual RA patients in clinical practice. To achieve significant disease suppression (e.g. “remission” or “minimal disease activity”) a target score of that composite index is identified. Remission can be defined as an absolute number on a composite index (e.g. DAS < 1.6 or DAS28 < 2.6) or as categorical criteria (e.g. ACR 5/6 criteria). The face validity of remission as defined by composite indices has been shown to surpass the one for the “criteria”. For effective therapy, frequent clinical assessments are needed. However, composite scores are rarely used to follow patients in clinical practice because they either employ extensive joint counts (DAS), require calculators to compute (DAS, DAS28, DAS28-CRP), or their results are not readily accessible for immediate decision making due to missing laboratory results (DAS, DAS28, DAS28-CRP and SDAI). Acute phase reactants (APR) are an integral component of all the current composite indices. How important is their contribution to the composite scores? It has been shown that as much as 85% of the variance in the DAS28 can be explained without ESR and 95% of the variances in the SDAI and the DAS28-CRP are explained by their composing clinical variables (i.e. without CRP).2 The contribution of APRs thus ranges between 5 and 15% for different indices. CDAI was developed capitalizing on this aspect. CDAI is a simple composite index obtained by the numerical summation of four clinical variables. These comprise 28 swollen and tender joint counts each (similar to DAS28) and patient and evaluator global assessment of disease activity in the visual analogue scale (0–10 each), with the total score ranging between 0 and 76. It has been shown to have good content, construct and face validity highlighting the fact that APR is not an absolute requirement in the context of disease activity scores. CDAI correlates well with DAS28CRP and the SDAI thus supporting the fact that transformation and/or weighing of the clinical variables does not confer an advantage compared with their simple numerical summation. CDAI has equivalent diagnostic accuracy to other composite measures like DAS28 and SDAI in classifying the disease activity states.3 CDAI has been shown to be better than DAS and DAS28 in defining remission. This is because