Background Cut-off points for disease activity scores (DAS) using a DAS28-CRP have been reported to be different than for DAS28-ESR in clinical trials and studies of established rheumatoid arthritis (RA)[1].

Objectives We aimed to evaluate the relationship of these in an early RA cohort.

Methods We estimated cut-off points for DAS28 using the C-Reactive Protein (CRP) as the acute phase reactant, (where normal CRP is <1.0 mg/dl) that corresponded to the DAS28, usually calculated with the erythrocyte sedimentation rate (ESR) for remission (REM), low disease activity (LDA), moderate disease activity (MDA) and high disease activity (HDA). Recent complete data from 882 early RA patients in the Canadian early ArThritis CoHort (CATCH) were used to calculate the Spearman’s rank correlation coefficient of DAS28 and DAS28-CRP measures. Receiver Operator Curves (ROC) were constructed to assess cut-off points of DAS28-CRP corresponding to DAS28. Each was calculated based on the best trade-off between sensitivity (sens) and specificity (spec) as (sens+spec)/2 ([1],[2]) and on the Matthews correlation coefficient (MCC). Patients were classified into different disease activity states based on cut-off values for DAS28 and DAS28-CRP. Kappa statistics were calculated to evaluate cut-off points. Statistical significance was defined as p <0.05.

Results Mean (SD) age was 53.8 (14.7). Disease duration was 5.9 (3.0) months. 74% were female, 85% Caucasian, and 18% current smokers. Mean (SD) DAS28 and DAS28-CRP scores were 3.0 (1.5) and 2.8 (1.3). A strong linear relationship between DAS28 and DAS28-CRP was seen [Spearman correlation 0.52 (p<0.0001); Pearson’s correlation 0.92 (p<0.0001)]. ROC curves were constructed to assess cut-off points of DAS28-CRP for REM, LDAS, MDAS corresponding to DAS28 scores of <2.6, <3.2 and <5.1. Two criteria were used to find the best cut-off points (Table). Higher sens, spec, negative and positivie predictive values were observed using the MCC (Table) and this was chosen as the final model to calculate cut-offs.

Best cut-off points based on Matthews correlation coefficient (MCC):

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Conclusions Given that a MCC accounts for true + false positives and negatives and is regarded as a balanced measure even if classes are of different sizes, we propose cut off points for DAS28-CRP based on real world patient measures to be DAS28-CRP<2.4 (REM), DAS28-CRP<2.9 (LDAS) and DAS28-CRP<4.8 (MDAS) and DAS28-CRP≥4.8 (HDAS)

References

1. Inoue E, et al. Ann Rheum Dis 2007; 66:407–9.

2. Aletaha D, et al. Arth & Rheum 2005;52:2625–36.

References

Acknowledgements The CATCH study was designed and implemented by the investigators and financially supported initially by Amgen Canada Inc. and Pfizer Canada Inc. via an unrestricted research grant since inception of CATCH. As of 2011, further support was provided by Hoffmann-La Roche Ltd., United Chemicals of Belgium (UCB) Canada Inc., Bristol-Myers Squibb Canada Co., Abbvie Inc, and Janssen Biotech Inc. (a wholly owned subsidiary of Johnson & Johnson Inc.)

Disclosure of Interest None Declared