THU0164 THE DAS28 BASED ON THE ERYTHROCYTE SEDIMENTATION RATE MAY OVERESTIMATE DISEASE ACTIVITY IN EARLY, TREATMENT-NAÏVE PATIENTS WITH RHEUMATOID ARTHRITIS WITH HIGH LEVELS OF RHEUMATOID FACTOR
Authors: Emanuele Bozzalla Cassione, Serena Bugatti, Francesca Benaglio, Garifallia Sakellariou, Antonio Manzo, Roberto Caporali, Carlomaurizio Montecucco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Disease activity in rheumatoid arthritis (RA) is commonly measured with the DAS28-ESR. However, ESR levels may be affected by factors not related to inflammation leading to possible disparities with the DAS28-CRP. In particular, increased levels of gammaglobulins may cause increase in ESR. In RA levels of autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) may be particularly high; however, their effect on the assessment of disease activity has not been investigated. <h3>Objectives:</h3> To evaluate whether positivity and levels of RF and ACPA determine discordance between the DAS28-ESR and the DAS28-CRP, impacting on disease activity stratification in RA. <h3>Methods:</h3> 578 early treatment-naïve RA patients (symptoms' duration &lt;12 months) consecutively recruited at our Early Arthritis Clinic between 2005 and 2014 were studied. Paired DAS28-ESR and DAS28-CRP were obtained at baseline and after 6 months of therapy with conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs). RF and ACPA were determined centrally on baseline sera, and levels were considered high when &gt;3 times the upper limit of normal (ULN). Agreement between the disease activity scores was compared using Bland-Altman statistics before and after stratification for autoantibody-positivity and levels. <h3>Results:</h3> Female/male ratio was 2.5:1, with mean (SD) age of 59.7 (14.8) years and median (IQR) symptoms' duration at inclusion of 15.6 (9.4 to 27.8) weeks. Mean DAS28-ESR values at baseline were 0.39 points higher compared to DAS28-CRP in the whole cohort, with more pronounced differences in females and subjects aged ≥65 years (<b>Table 1</b>). Collectively RF-positive patients had significantly higher discrepancies compared to –negative subjects (mean [SD] difference 0.45 [0.46] vs 0.35 [0.47], p=0.03), particularly in females irrespective of age. The highest disagreement was recognized in patients with high autoantibody levels; females with RF &gt;3 ULN had DAS28-ESR scores 0.56 points higher. Disparities in these patients impacted on disease activity stratification, as more RF-high females were in DAS28-ESR high disease activity compared with DAS28-CRP (43.1% vs 23%, p&lt;0.001). In contrast, ACPA-positivity did not affect the agreement between the two disease activity indices (<b>Table 1</b>). After 6 months of treatment with csDMARDs discrepancies between the DAS28-ESR and DAS28-CRP in RF-positive patients was reduced but still significant in association with levels &gt;3 ULN (mean difference [95% CI] 0.44 [0.33-0.55]). <h3>Conclusion:</h3> In patients with early treatment-naïve RA, the DAS28-ESR and DAS28-CRP are not inter-exchangeable. In particular, the DAS28-ESR may overestimate disease activity when levels of RF are high. These findings suggest that disease assessment for treat-to-target approaches should take into account additional factors such as autoantibody-positivity. <h3>Disclosure of Interests:</h3> Emanuele Bozzalla Cassione: None declared, Serena Bugatti Speakers bureau: Bristol-Myers Squibb, Celgene, Lilly, Novartis, Sanofi, Janssen, Francesca Benaglio: None declared, Garifallia Sakellariou: None declared, Antonio Manzo: None declared, Roberto Caporali Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Roche, Genzyme, Lilly, MSD, Pfizer, UCB, Carlomaurizio Montecucco Speakers bureau: AbbVie, Bristol-Myers Squibb, Celgene, Sanofi, Genzyme, Lilly, MSD, Pfizer, UCB