Background/Purpose: Anti-CarPA have been shown to predict development of rheumatoid arthritis (RA) in patients with arthralgia.  However, little is known about their association with disease activity and long term outcomes such as disability; or whether they provide additional prognostic information to anti-citrullinated protein antibodies (ACPA).  The aims of this study were (i)to investigate the association between anti-CarPA status, disability and disease activity over 20 years follow up in patients with early inflammatory arthritis (EIA), and (ii)to examine these associations in the subgroups of patients with and without ACPA.

Methods:  Adults presenting to primary care with recent onset swelling of ≥2 joints for ≥4 weeks were recruited to NOAR since 1990.  Baseline assessment included joint examination, smoking status and patient recording of the HAQ.  CRP, rheumatoid factor (RF), ACPA and anti-CarPA were measured on stored sera obtained at baseline or in the first year of follow up.  DAS28-CRP was calculated and 2010 ACR/EULAR classification criteria for RA were applied.  Further HAQ scores were obtained at 1, 2, 3, 5, 7, 10, 12, 15 and 20 years follow up, and DAS28-CRP every 5 years.  Generalized estimating equations (GEE) were used to test the association between anti-CarPA status and longitudinal HAQ and DAS28 scores including a time interaction term; then additionally adjusting for age, gender, smoking status, year of inclusion and ACPA status.  The analyses were repeated in the ACPA negative and positive subgroups and in patients who fulfilled RA classification criteria without adjustment for ACPA.

Results:  1995 patients were included; 1310 (66%) were female, median age at onset (IQR) was 55 years (43-66) and median symptom duration (IQR) was 33 weeks (17-68).  Anti-CarPA were positive in 460 (23%) patients and 1221 (61%) satisfied the 2010 ACR/EULAR classification criteria for RA. 539 (26%) were current smokers.  ACPA were tested in 1465 patients, 373 (25%) were positive. Median follow up time (IQR) was 7 years (5-11).  Baseline median HAQ and DAS28 were higher in anti-CarPA positive vs negative patients (1.125 vs 0.875 and 4.23 vs 3.73 respectively). In the GEE analysis, patients who were anti-CarPA positive had significantly more disability over time and higher levels of disease activity than those who were negative; multivariate model for the HAQ including adjustment for ACPA gave a β coefficient (95% confidence interval) 0.13 (0.03-0.23) (Table 1).  Statistically significant associations were also seen in the ACPA negative subgroups.  In the ACPA positive and RA subgroups there were significant associations with DAS28 and trends approaching statistical significance with HAQ scores. 

Conclusion:   The presence of anti-CarPA is associated with increased burden of disability and higher disease activity over time in patients with EIA.  Our results suggest anti-CarPA may be useful in identifying ACPA negative patients with poor prognosis.

Table 1. Association between anti-CarpA positivity and HAQ and DAS28 throughout follow up
	Total cohort n=1995 β coefficient(95% CI)	ACPA –ve n=1092 β coefficient(95% CI)	ACPA +ve n=373 β coefficient(95% CI)	RA patients n=1221 β coefficient(95% CI)
HAQ
Univariate*	0.20 (0.13-0.28)	0.16 (0.02-0.31)	0.13 (-0.01-0.28)	0.06 (-0.03-0.15)
Multivariate$	0.13 (0.03-0.23)	0.15 (0.02-0.29)	0.12 (-0.03-0.28)	0.08 (-0.01-0.17)
DAS28
Univariate*	0.47 (0.33-0.61)	0.29 (0.03-0.55)	0.30 (0.03-0.56)	0.16 (0.01-0.32)
Multivariate$	0.31 (0.12-0.49)	0.37 (0.11-0.63)	0.30 (0.02-0.57)	0.21 (0.04-0.37)
*includes interaction term with time variable $adjusted for interaction term with time variable, age at symptom onset, gender, baseline smoking status and year of inclusion in the cohort. ACPA status was also included as a covariate in the total cohort multivariate model.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-carbamylated-antibodies-anti-carpa-are-associated-with-long-term-disability-and-increased-disease-activity-in-patients-with-early-inflammatory-arthritis-results-from-the-norfolk-arthritis-regi/