Abstract
ANTI-CARBAMYLATED PROTEIN POSITIVITY PREDICTS DAS28-REMISSION AT 12 MONTHS IN PATIENTS WITH EARLY RHEUMATOID ARTHRITIS: RESULTS FROM THE SINGAPORE EARLY ARTHRITIS COHORT
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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 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
<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 & 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.
Citation: Ann Rheum Dis, volume 79, supplement 1, year 2020, page 586Session: Rheumatoid arthritis - prognosis, predictors and outcome
(Poster Presentations)
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