Background/Purpose: In most patients with rheumatoid arthritis (RA) the 28-Joint Disease Activity Score (DAS28) values calculated using C-reactive protein (CRP) are lower than those calculated using erythrocyte sedimentation rate (ESR). Since validated thresholds for categorizing disease activity are available for DAS28-ESR only, their application for DAS28-CRP has become common in clinical practice and clinical trials. Recently, Fleishmann et al. proposed new DAS28-CRP cut-offs for definition of remission, low and high disease activity [1, 2]. We aimed to evaluate here the use of the newly proposed thresholds for categorizing disease activity in relation to the validated DAS28-ESR cut-offs in DMARD-naïve patients with early RA.

Methods: We used blinded data from the ongoing trial with the EP4 receptor antagonist CR6086 in early rheumatoid arthritis, DMARD-naïve patients (the CREATIVE study). This is a randomized, placebo-controlled, double-blind, dose response, Phase IIb, multicentre trial of CR6086 administered for 12 weeks in combination with methotrexate (NCT03163966). The study consists of a baseline evaluation and 4 post-baseline visits at the following time-points: weeks 3, 6, 9 and 12. DAS28-CRP and DAS28-ESR were determined at each visit and their correlation was analysed using Spearman’s coefficient. Agreement between the newly proposed DAS28-CRP thresholds for remission (<2.4), low (≤2.9) and high disease activity (>4.6) and the validated DAS28-ESR cut-offs (<2.6, ≤3.2 and >5.1, respectively) was determined by k coefficient, sensitivity and specificity. Results are presented as number of visits, regardless of patients and time-points.

Results: A total of 146 patients newly diagnosed with RA by the 2010 ACR/EULAR classification criteria had been randomized in EU/non-EU countries at the time of the data cut-off (May 2018). Overall, data for the analyses were available for 527 visits. DAS28-CRP values were generally lower than DAS28-ESR values, but the 2 measures were highly correlated (Spearman’s correlation 0.94). Based on the validated DAS28-ESR cut-offs, remission was determined in 17 visits, low disease activity in 22 visits, moderate disease activity in 202 visits, and high disease activity in 286 visits. The corresponding values obtained applying the newly proposed DAS28-CRP thresholds were 18, 27, 181 and 301 visits, respectively. A good agreement was reached against the validated DAS28-ESR cut-offs (k=0.67) and sensitivity was particularly high for the high disease activity category (90%).

Conclusion: Analysis of blinded data from the ongoing Phase IIb trial with CR6086 indicated that the newly proposed DAS28-CRP thresholds for remission, low and high disease activity are consistent with the validated DAS28-ESR cut-offs, thus supporting their use in clinical trial and clinical practice.

[1] Fleischmann R et al. Ann Rheum Dis. 2015; 74:1132–1137.

[2] Fleischmann RM et al. RMD Open 2017;3:e000382.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/das28-crp-versus-das28-esr-and-thresholds-for-disease-activity-category-blinded-data-from-the-ongoing-phase-iib-trial-with-the-ep4-receptor-antagonist-cr6086-in-dmard-naive-patients-with-early-rheuma/