ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2595

Autoantibodies to Citrullinated Fibrinogen, Anti-CCP2 and Anti-MCV Antibodies in Early Rheumatoid Arthritis Patients with Rapid Radiographic Progression at 1-Year

Yannick Degboé1, Arnaud Constantin2, Delphine Nigon3, Gabriel Tobon4, Martin Cornillet5, Thierry Schaeverbeke6, Gilles Chiocchia7, Pascale Nicaise-Roland8, Leonor Nogueira9, Guy Serre5,10,11, Alain G. Cantagrel12 and Adeline Ruyssen Witrand13,14, 1Rheumatology, Rheumatology Center, Purpan University Hospital, Toulouse, France, 2Inserm U558, Rheumatology Center, Purpan University Hospital, Toulouse, France, 3CHU Purpan, Toulouse, France, 4Rheumatology Department, la Cavale Blanche Hospital, Brest, France, 5Service de Biologie Cellulaire, C.H.U. Purpan, Toulouse, France, 6CHU Bordeaux, Bordeaux, France, 7Immunology-Rheumatology, INSERM U1173, paris, France, 8Immunology Department, Bichat Claude-bernard, Universitary Hospital, APHP, Paris, France, 9Immunology, UMR CNRS 5165, INSERM 1056, Toulouse, France, 10Cell Biology, Purpan University Hospital, Toulouse, France, 11Unité Différenciation Épidermique et Autoimmunité Rhumatoïde, Unité Mixte de Recherche, INSERM,Toulouse, France, Toulouse, France, 12Rheumatology, Centre Hospitalier Universitaire, Toulouse Purpan, Toulouse, France, 13Rheumatolgy, CHU Purpan - Hôpital Pierre-Paul Riquet, Toulouse, France, 14UMR 1027, Inserm, Toulouse, France

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: , , ,

Session Information

Date: Tuesday, November 10, 2015

Title: Rheumatoid Arthritis - Clinical Aspects Poster Session III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: We compared the ability of anti-CCP2, anti-mutated citrullinated vimentin (anti-MCV) and anti-citrullinated fibrinogen (AhFibA) antibodies to predict 1-year rapid radiographic progression (RRP; total Sharp score variation ≥ 5 points), in early rheumatoid arthritis (RA).

Methods: We analyzed 566 patients from the ESPOIR cohort with early RA fulfilling the 2010 ACR/EULAR criteria at inclusion. Prediction of 1-year RRP was analyzed by receiver operating characteristic (ROC) curves for the 3 ACPA assayed by ELISA on baseline sera. One-year RRP risk was assessed by ACPA titers. Logistic multivariate regression was used to analyze RRP risk in terms either of positivity or of titer: high, >3 times the cut-off (>3N) and low (1 to 3N).

Results: 333 patients were positive for at least one of the three ACPA tests and 145 patients displayed RRP (Table 1). The areas under the ROC curves were similar for the 3 antibodies, about 0.60. Low+ anti-MCV titers were not associated with RRP (Odds ratio (OR) 0.68; 95% confidence interval (95%CI) 0.29-1.59), whereas low+ anti-CCP2 titers (OR 3.80; 95%CI 1.11-13.10) and low+ AhFibA titers (OR 2.39; 95%CI 1.04-5.49) were significantly associated (Table 2). In multivariate analysis, 1-year RRP was associated with high anti-MCV titers (OR 2.17; 95%CI 1.45-3.24), with anti-CCP2 positivity (OR 2.14; 95%CI 1.43-3.21) and with AhFibA positivity (OR 2.39; 95%CI 1.57-3.63) (Table 3).

Conclusion: Anti-CCP2 antibodies and AhFibA were predictive of 1-year RRP in early RA whatever their titer was, whereas only high anti-MCV antibodies titers were predictive potentially making them more discriminant to predict 1-year RRP risk.

Table 1. Demographic, biologic and radiographic data for patients with early rheumatoid arthritis

 

Patients

(n = 566)

Patients without RRP at 1 year

(n = 421)

Patients with RRP at 1 year

(n = 145)

P value

DEMOGRAPHIC DATA

Age, years, median (IQR)

50.5 (40.2-57.0)

49.9 (40.0-56.7)

52.4 (41.7-58.6)

NS

Women, no. (%)

445 (78.6)

336 (79.8)

109 (75.2)

NS

Smokers, no. (%)

272 (48.1)

204 (48.5)

68 (46.9)

NS

Disease duration, months, median (IQR)

5.0 (3.1-7.4)

4.8 (3.0-7.1)

5.2 (3.5-7.8)

NS

BIOLOGIC DATA

ESR, mm/1h, median (IQR)

22 (12-37)

20 (12-34)

27 (14-49)

 0.0063

CRP level, mg/L, median (IQR)

9 (0-21)

8 (0-18)

14 (5-36)

< 0.0001

≥ 1 allele encoding HLADRB1 SE, no. (%)

292 (54.0%)

205 (50.9)

87 (63.0)

0.0133

RF+, no. (%)

307 (54.2)

208 (49.4)

99 (68.3)

< 0.0001

Anti-CCP2 titers, no. (%)

  negative

  low

  high

295 (52.1)

11 (1.9)

260 (45.9)

242 (57.5)

6 (1.4)

173 (41.1)

53 (36.5)

5 (3.4)

87 (60.0)

< 0.0001

Anti-MCV titers, no. (%)

  negative

  low

  high

268 (47.3)

51 (9.0)

247 (43.6)

217 (51.5)

44 (10.4)

160 (38.0)

51 (35.2)

7 (4.8)

87 (60.0)

< 0.0001

AhFibA titers, no. (%)

  negative

  low

  high

272 (48.1)

30 (5.3)

264 (46.6)

225 (53.4)

20 (4.8)

176 (41.8)

47 (32.4)

10 (6.9)

88 (60.7)

< 0.0001

RADIOGRAPHIC DATA

Baseline mTSS, median (IQR)

3 (0-7)

2 (0-7)

3 (0-8)

NS

mTSS at 1 year, median (IQR)

6 (2-12)

4 (2-8)

13 (8-19)

< 0.0001

mTSS progression, median (IQR)

2 (0-5)

0 (0-2)

8 (6-11)

< 0.0001

RRP = rapid radiographic progression; SE = presence of at least one allele of the shared epitope of HLA-DRB1; ESR = erythryocyte sedimentation rate; CRP = C-reactive protein; IQR = interquartile range; RF = rheumatoid factor; mTSS = van der Heijde modified Total Sharp Score

Table 2. One-year rapid radiographic progression (RRP) and baseline ACPA titers (anti-CCP2, anti-MCV, AhFibA)

Antibody titers

No. of patients

with RRP(%) 

OR [95%CI]

p value (χ2)

Anti-CCP2

Negative

53 (18.0)

1

–

Low titer (≤3N)

5 (45.5)

3.80 [1.11–13.10]

0.0226

High titer (>3N)

87 (33.5)

2.30 [1.54–3.43]

< 0.0001

p value (OR trend)

2.9 10-5

Anti-MCV

Negative

51 (19.0)

1

–

Low titer (≤3N)

7 (13.7)

0.68 [0.29–1.59]

NS

High titer (>3N)

87 (60.0)

2.31 [1.54–3.48]

< 0.0001

p value (OR trend)

3.0 10-5

AhFibA

Negative

47 (17.3)

1

–

Low titer (≤3N)

10 (33.3)

2.39 [1.04–5.49]

0.0332

High titer (>3N)

88 (33.3)

2.39 [1.58–3.62]

< 0.0001

p value (OR trend)

2.1 10-5

p value = χ2 test, with negative ACPA rates as the reference. p value (OR trend) = test of trend

Table 3. Multivariate analysis of variables associated with 1-year RRP 

 

OR

95%CI

P value

Model 1: assessing anti-CCP2

AUC 0.6491 (95%CI 0.5978–0.7003)

Anti-CCP2 positivity

2.15

1.43–3.21

<0.0001

CRP level (> 10 mg/L)

1.73

1.15–2.58

0.007

Erosions at baseline

1.50

1.00–2.25

0.049

Model 2: assessing anti-MCV

AUC 0.6304 (95%CI 0.5784–0.6825)

Anti-MCV positivity

Discarded during logistic regression

RF positivity

2.12

1.40–3.20

<0.0001

CRP level (> 10 mg/L)

1.80

1.21–2.67

0.004

Model 3: assessing AhFibA

AUC 0.6536 (95%CI 0.6017–0.7055)

AhFibA positivity

 2.39

1.57–3.63

<0.0001

CRP level (> 10 mg/L)

 1.68

1.13–2.51

0.011

Age at RA onset

 1.02

1.00–1.04

0.031

Model 4: assessing high ACPA titer (>3N)

AUC 0.6480 (95%CI 0.5958–0.7003)

High anti-CCP2 or AhFibA titers

Discarded during logistic regression

High anti-MCV titers

2.17

1.45–3.24

<0.0001

CRP level (> 10 mg/L)

1.69

1.13–2.53

0.010

Erosions at baseline

1.50

1.00–2.25

0.049

AUC = area under (the receiver operating characteristic) curve

Disclosure: Y. Degboé, None; A. Constantin, None; D. Nigon, None; G. Tobon, None; M. Cornillet, None; T. Schaeverbeke, None; G. Chiocchia, None; P. Nicaise-Roland, None; L. Nogueira, None; G. Serre, None; A. G. Cantagrel, None; A. Ruyssen Witrand, None.

To cite this abstract in AMA style:

Degboé Y, Constantin A, Nigon D, Tobon G, Cornillet M, Schaeverbeke T, Chiocchia G, Nicaise-Roland P, Nogueira L, Serre G, Cantagrel AG, Ruyssen Witrand A. Autoantibodies to Citrullinated Fibrinogen, Anti-CCP2 and Anti-MCV Antibodies in Early Rheumatoid Arthritis Patients with Rapid Radiographic Progression at 1-Year [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/autoantibodies-to-citrullinated-fibrinogen-anti-ccp2-and-anti-mcv-antibodies-in-early-rheumatoid-arthritis-patients-with-rapid-radiographic-progression-at-1-year/. Accessed .

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