FRI0033 ANTI-CARBAMYLATED PROTEIN POSITIVITY PREDICTS DAS28-REMISSION AT 12 MONTHS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RESULTS FROM THE SINGAPORE EARLY ARTHRITIS COHORT
Authors: J. Cho, A. Mak, S. Agrawal, P. Dhanasekaran, L. K. Teoh, P. Cheung, M. Lahiri
Journal: Annals of the Rheumatic Diseases (2020)

Background: Anti-carbamylated protein antibody (anti-carp) positivity has been associated with poorer outcomes in Western cohorts of early rheumatoid arthritis; however, it is unknown if this applies to Asians. Objectives: We determined whether anti-carp predicted DAS28-remission, disability and radiographic progression in a multi-ethnic Asian ERA cohort. Methods: Patients with physician diagnosed ERA (symptom duration ≤1 year) were recruited from the Singapore Early Arthritis Cohort (n= 317) by convenience sampling. Serum anti-carp was measured cross-sectionally using a commercial ELISA (SincereBio). The test was repeated in 40 healthy individuals to establish the optimal sensitivity and specificity for the diagnosis of RA via a receiver operating curve. Disease activity (DAS28-ESR or DAS28-CRP) was recorded at baseline, 3, 6 and 12 months. Two independent accessors quantified the radiographic damage at baseline and at follow-up using the modified Sharp van der Heijde score (mSS). We used multivariable logistic regression to determine whether anti-carp predicted the following outcomes; (i) DAS-28 remission at 12 months, (ii) any disability (mHAQ&gt;0) at 12 months and (iii) radiographic progression (any increase in the mSS). In each regression model, we chose covariates known to influence the dependent variable in our cohort or from literature. Results: One hundred patients were recruited, of mean age (SD) 49.8 (12.5) years, median (IQR) disease duration 10.2 (6.9-15.1) weeks at cohort entry and baseline median DAS-28 4.5 (2.9-5.9) (Table 1). The anti-carp assay was performed after a median (IQR) disease duration of 2.24 (1.82-3.14) years. 93 patients had baseline hand radiographs and 66 had follow-up hand radiographs after ≥ 12 months. Receiver operating characteristics curve yielded optimal sensitivity (95%) and specificity (60%) for the diagnosis of RA at 1.60OD. Therefore, 60 patients were anti-carp positive and 35 patients (37.2%) were positive for RF, ACPA and anti-carp (Figure 1). Anti-carp positivity independently predicted DAS28-remission at 12 months (OR 3.41, 95% CI 1.08-10.7, p =0.04) (Table 2). Anti-carp positivity did not predict disability at 12 months (OR 0.61, 95% CI 0.18-2.07, p =0.43) or radiographic progression (OR 0.23, 95% CI 0.03-2.03, p =0.18). Table 1. Predictors of DAS28-remission at 12 months Variable N (% ) Univariable Logistic Regression Multivariable Logistic Regression OR p OR (CI) SE p Anti-carp 60 (60) 3.0 (1.31−6.88) 0.01 3.41 (1.08−10.7) 1.99 0.04 Serology RF and ACPA negative 31 (33.0) Ref Either RF or ACPA positive 11 (11.7) 0.99 (0.25−3.93) 0.99 1.10 (0.17−7.04) 1.04 0.92 RF and ACPA positive 52 (55.3) 1.12 (0.45−2.75) 0.80 0.89 (0.28−2.81) 0.52 0.84 Baseline DAS28 Remission 17 (17.4) Ref Low DA 10 (10.2) 0.50 (0.05−4.67) 0.54 0.13 (0.01−1.67) 0.17 0.12 Mod DA 32 (32.7) 0.29 (0.05−1.65) 0.16 0.10 (0.02−0.68) 0.10 0.02 High DA 39 (39.8) 0.18 (0.04−0.90) 0.04 0.06 (0.01−0.41) 0.06 &lt;0.01 Combination csDMARDs or biologic DMARD 74 (74) 1.13 (0.46−2.76) 0.80 1.97 (0.58−6.67) 1.23 0.28 Radiographic damage at baseline 11 (20) 1.79 (0.65−4.95) 0.26 1.27 (0.33-4.95) 0.88 0.73 Tertiary education 23 (38.3) 0.77 (0.34-1.77) 0.54 0.42 (0.12-1.45) 0.27 0.17 Ethnicity Chinese 42 (70) Ref Malay 39 (68.4) 0.61 (0.22-1.71) 0.35 0.56 (0.14-2.25) 0.40 0.41 Indian 8 (13.3) 0.60 (0.20-1.77) 0.35 0.79 (0.20-3.13) 0.56 0.74 Females 46 (76.7) 0.43 (0.17-1.11) 0.08 0.48 (0.13-1.85) 0.33 0.29 Conclusion: Contrary to previous studies done on Western cohorts where anti-carp predicted worse outcomes, anti-carp positivity predicted DAS28-remission at 12 months in our multi-ethnic Asian cohort. This suggests that different genetic and environmental determinants account for anti-carp expression in patients with RA. Disclosure of Interests: Jiacai Cho: None declared, Anselm Mak Speakers bureau: Professor Anselm Mak has been paid as a speaker for Johnson &amp; Johnson., Sachin Agrawal: None declared, Preeti Dhanasekaran: None declared, Lay Kheng Teoh: None declared, Peter Cheung: None declared, Manjari Lahiri Grant/research support from: Manjari Lahiri is the site principal investigator for the Singapore National Biologics Register, which is a multi-pharmaceutical funded register, in which industry sponsors provide support through the Chapter of Rheumatologists, Singapore. Dr Lahiri does not personally receive any remuneration.