Prognosis Of Seronegative Patients In a Large Prospective Cohort Of Patients With Early Inflammatory Arthritis

Lillian J. Barra¹, Janet E. Pope², Boulos Haraoui³, Carol A. Hitchon⁴, J. Carter Thorne⁵, Edward C. Keystone^6,7, Diane Tin⁸, Gilles Boire⁹ and Vivian P. Bykerk¹⁰, ¹Medicine, Division of Rheumatology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, ²Medicine, Divsion of Rheumatology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada, ³Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada, ⁴Rheumatology, University of Manitoba, Winnipeg, MB, Canada, ⁵Southlake Regional Health Centre, Newmarket, ON, Canada, ⁶Department of Medicine, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada, ⁷Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, University of Toronto, Toronto, ON, Canada, ⁸The Arthritis Program, Southlake Regional Health Centre, Newmarket, ON, Canada, ⁹Rheumatology Division, Centre Hospitalier Universitaire de Sherbrooke, Université de Sherbrooke, Sherbrooke, QC, Canada, ¹⁰Rheumatology, Hospital for Special Surgery, Weill Cornell Medical College, New York, NY

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: anti-CCP antibodies, anti-citrullinated protein/peptide antibodies (ACPA), Prognostic factors and rheumatoid arthritis (RA), Rheumatoid Factor

Session Information

Title: Rheumatoid Arthritis - Clinical Aspects II: Predictors of Disease Course in Rheumatoid Arthritis - Treatment Approaches

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid Factor (RF) and anti-Cyclic Citrullinated Peptide (anti-CCP) are believed to be associated with more severe clinical outcomes; however, studies in Early Inflammatory Arthritis (EIA) have yielded conflicting results. The objective of this study is to determine the prognosis of baseline anti-CCP and RF-negative patients at 12 months follow-up in the Canadian Early Rheumatoid Arthritis cohort (CATCH).

Methods: Data were collected on patients enrolled in CATCH, a multicentre, observational, prospective inception cohort of patients with Early Inflammatory Arthritis (EIA). Treatment was based on physician discretion. IgM RF was measured and depending on the site, two different anti-CCP2 IgG (CCP) kits were used (Euroimmune™ and Inova™). Disease activity was determined using the Disease Activity Score-28 (DAS28) and remission was defined as a DAS28<2.6. Presence of erosions was determined using plain radiographs of the hands and feet. Follow-up was 12 months. Multiple logistic regression was used to account for confounders.

Results: 216/841 (26%) of patients were negative for both RF and anti-CCP2. These patients were older (57 years old) and more likely male (31%) compared to seropositive patients (51 years old and 23% male), p<0.001. Seronegative patients were less likely to meet 1987 ACR and 2010 ACR/EULAR criteria for RA, however, at baseline they had higher swollen joint counts (SJC) (9 vs 6), more erosive disease (32% vs. 23%) and higher DAS28 scores (5.00 vs. 4.75), p<0.05. Seronegative patients had shorter duration of symptoms (166 days vs. 192, p=0.007). The initiation of DMARDs, biologics and steroids was similar between the two groups. At 12 months follow-up, seronegative patients had greater reductions compared to seropositive patients in SJC (7 vs.4) and similar DAS28 scores (2.97 vs. 2.83); p=0.0017 and p=0.3, respectively. Accounting for confounders, seronegative patients were as likely to achieve DAS28 remission as seropositive patients (OR 1.18; 95%CI: 0.70-1.99), however, they were less likely to have erosive disease at follow-up (OR 0.43; 95%CI: 0.19-0.95, p<0.04).

Conclusion: Although seronegative EIA patients have higher disease activity at baseline compared to seropositive patients, they have a good response to treatment and are less likely to have erosive disease at follow-up.

	Seronegative	Seropositive	p-value
*Baseline*:
N	216	625
Age, mean years (SD)	57 (15)	51 (14)	<0.0001
Male	67 (31)	145 (23.2)	0.0225
Symptom Duration, days mean (SD)	166 (87)	192 (98)	0.0007
Ever Smoker	111 (51.6)	369 (59.1)	0.055
SJC28, mean (SD)	8.8 (6.8)	6.5 (5.6)	<0.0001
TJC28, mean (SD)	9.3 (7.2)	7.1 (6)	<0.0001
ESR, mean (SD)	24.88 (22)	27.26 (22.59)	0.6513
CRP, mean (SD) (mg/L)	13.77 (18.22)	13.39 (16.94)	0.7864
Erosions	58/181 (32)	124/517 (24)	0.0335
DAS28, mean (SD)	5.00 (1.6)	4.75 (1.49)	0.0493
1987 ACR RA criteria	131 (60.7)	442 (70.7)	0.007
2010 ACR/ EULAR RA criteria	96 (44.4)	482 (77.1)	<0.0001
DMARDs	186 (86)	550 (88)	0.4567
Biologics	5 (2.4)	19 (3)
Corticosteroids	125 (58)	319 (51.1)	0.0859
*Follow-up*
N	147	474
DAS28 Remission OR (95%CI)	80 (54) 1.18 (0.70-1.99)	269 (57) Reference	0.6190 0.5114
Erosive Disease OR (95%CI)	14/66 (21) 0.43 (0.19-0.95)	85/279 (30)	0.1350 0.0366
* Values are N (%) unless otherwise indicated. CCP=anti-cyclic Citrullinated Peptide 2, RF= Rheumatoid Factor, SJC28= Swollen Joint Count 28, TJC28= Tender Joint Count 28, ESR= Erythrocyte Sedimentation Rate, CRP= C-Reactive Protein, DAS28= Disease Activity Score 28, DMARDs= Disease Modifying Anti-Rheumatic Drugs.

Disclosure:

L. J. Barra,
None;

J. E. Pope,
None;

B. Haraoui,
None;

C. A. Hitchon,
None;

J. C. Thorne,
None;

E. C. Keystone,
None;

D. Tin,
None;

G. Boire,
None;

V. P. Bykerk,
None.

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