Abstract
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>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 monthsVariableN (%)Univariable Logistic RegressionMultivariable Logistic RegressionORpOR (CI)SEpAnti-carp60 (60)3.0 (1.31−6.88)0.013.41 (1.08−10.7)1.990.04SerologyRF and ACPA negative31 (33.0)RefEither RF or ACPA positive11 (11.7)0.99 (0.25−3.93)0.991.10 (0.17−7.04)1.040.92RF and ACPA positive52 (55.3)1.12 (0.45−2.75)0.800.89 (0.28−2.81)0.520.84Baseline DAS28Remission17 (17.4)RefLow DA10 (10.2)0.50 (0.05−4.67)0.540.13 (0.01−1.67)0.170.12Mod DA32 (32.7)0.29 (0.05−1.65)0.160.10 (0.02−0.68)0.100.02High DA39 (39.8)0.18 (0.04−0.90)0.040.06 (0.01−0.41)0.06<0.01Combination csDMARDs or biologic DMARD74 (74)1.13 (0.46−2.76)0.801.97 (0.58−6.67)1.230.28Radiographic damage at baseline11 (20)1.79 (0.65−4.95)0.261.27 (0.33-4.95)0.880.73Tertiary education23 (38.3)0.77 (0.34-1.77)0.540.42 (0.12-1.45)0.270.17EthnicityChinese42 (70)RefMalay39 (68.4)0.61 (0.22-1.71)0.350.56 (0.14-2.25)0.400.41Indian8 (13.3)0.60 (0.20-1.77)0.350.79 (0.20-3.13)0.560.74Females46 (76.7)0.43 (0.17-1.11)0.080.48 (0.13-1.85)0.330.29Conclusion: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 & 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.
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