ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 71

Association of Shared Epitope and Poor Prognostic Factors in RA

Evo Alemao1, Joshua Bryson1, Christine K Iannaccone2, Michelle Frits2, Nancy A. Shadick3 and Michael Weinblatt2, 1Bristol-Myers Squibb, Princeton, NJ, 2Brigham and Women’s Hospital, Boston, MA, 3Brigham and Women's Hospital, Boston, MA

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Date: Sunday, October 21, 2018

Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster I

Session Type: ACR Poster Session A

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

Background/Purpose: There is a strong genetic association between RA and human leukocyte antigen (HLA) regions, particularly HLA-DRB1 alleles with the shared epitope (SE). SE alleles are associated with seropositivity, erosions and higher disease activity (DA) in RA. We evaluated the association between SE alleles and multiple poor prognostic factors (PPFs) of seropositive (anti-citrullinated protein antibody and/or RF) and erosive RA, and changes in DA. Methods: We analyzed patients (pts) enrolled in a large sequential RA registry started in 2003; most had established RA and annual clinical evaluations. Pts with baseline (BL) data on SE status were included. A commercially available kit was used for HLA genotyping. HLA-DRB1 serotypes were assessed from DNA sequences using allele-specific polymerase chain reaction methods and categorized as pts with 0, 1 or 2 SE alleles. Association of multiple PPFs and SE status was evaluated using multinomial logistic models; association between change in DA and SE status was analyzed using linear regression models with age, sex, disease duration (DD), co-morbidities and biologic DMARDs as covariates. Results: Of 689 pts with RA, 0, 1 and 2 SE alleles were reported in 241 (35.0%), 275 (40.0%) and 173 (25.1%) pts, respectively. At BL, pts with SE alleles (vs 0) were more likely to have PPFs and had longer DD and higher DA (Table 1). Odds ratio (OR) for seropositive erosive RA in pts with 2 and 1 SE alleles (vs 0) was 5.44 (95% CI 2.39, 12.39) and 2.87 (1.32, 6.23; Fig), respectively. OR for double seropositivity in pts with 2 and 1 SE alleles (vs 0) was 4.27 (95% CI 2.51, 7.28) and 2.56 (1.66, 3.94), respectively. In total, 551 pts had DA measures at BL and 1 year. After controlling for BL covariates, pts with SE (vs 0 SE) had a mean increase in DAS28 (CRP) of 0.24 (p=0.031), CDAI of 2.71 (p=0.027) and SDAI of 3.25 (p=0.013; Table 2).

Conclusion: Pts with SE alleles are more likely to have multiple PPFs; pts with 2 SE alleles are 5 times more likely to be seropositive with erosive RA and 4 times more likely to be double positive. Pts with SE alleles also had an increase in DA over time with standard-of-care treatment.

Original abstract © EULAR/BMJ. First presented at EULAR 2018 and published in Ann Rheum Dis; 10.1136/annrheumdis-2018-eular.1657. Any reprints, promotional options, education material etc have to be done through the original source (ARD/BMJ).

 

 

Table 1. Baseline Characteristics by SE Status

 

0 SE alleles

(n=241)

1 SE allele

(n=275)

2 SE alleles

(n=173)

Mean (SD) age, years

57.7 (13.6)

58 (13.9)

57.8 (13.6)

Female sex, n (%)

202 (83.8)

219 (79.6)

141 (81.5)

Mean (SD) RA duration, years

12.9 (12.1)

17 (13.3)

16.1 (12.2)

Biologic DMARDs, n (%)

83 (34.4)

145 (52.7)

83 (48.0)

ACPA+, n (%)

118 (49.0)

196 (71.3)

137 (79.2)

Erosions, n (%)

116 (48.1)

168 (61.1)

114 (65.9)

RF+, n (%)

120 (49.8)

195 (70.9)

128 (74.0)

Double positive, n (%)

100 (41.5)

174 (63.3)

121 (69.9)

DAS28 (CRP), mean (SD)

3.8 (1.5)

4.2 (1.6)

4.3 (1.6)

ACPA=anti-citrullinated protein antibody; SE=shared epitope

 

 

Table 2. Multivariate Analysis of Impact of SE Status on Change in DA

 

DAS28 (CRP) model

CDAI model

SDAI model

Coefficient

p value

Coefficient

p value

Coefficient

p value

1 or 2 SE alleles (vs 0 SE)

0.24

0.031

2.71

0.027

3.25

0.013

Baseline DA

–0.41

<0.001

–0.46

<0.001

–0.48

<0.001

Age, years

0.01

0.271

0.04

0.367

0.04

0.406

Female (vs male)

0.11

0.435

2.52

0.099

2.12

0.198

No. of co-morbidities

0.11

0.003

1.25

0.003

1.42

0.002

Biologic DMARD (yes vs no)

0.41

<0.001

3.79

0.002

4.09

0.001

Adjusted R-square

0.23

0.27

0.29

DA=disease activity; SE=shared epitope

 

   

Disclosure: E. Alemao, Bristol-Myers Squibb, 1, 3; J. Bryson, Bristol-Myers Squibb, 1, 3; C. K. Iannaccone, None; M. Frits, None; N. A. Shadick, Amgen, Mallinckrodt, Bristol-Myers Squibb, Sanofi-Regeneron, 2,Bristol-Myers Squibb, 5; M. Weinblatt, Amgen, Crescendo Bioscience, Bristol-Myers Squibb, Sanofi/Regeneron, 2,AbbVie, Ablynx, Amgen, Bristol-Myers Squibb, Canfite, Corrona, Crescendo, GSK, Gilead, Lilly, Lycera, Merck, Momenta, Novartis, Pfizer, Roche, Samsung, Set Point, UCB, Vertex, 5.

To cite this abstract in AMA style:

Alemao E, Bryson J, Iannaccone CK, Frits M, Shadick NA, Weinblatt M. Association of Shared Epitope and Poor Prognostic Factors in RA [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/association-of-shared-epitope-and-poor-prognostic-factors-in-ra/. Accessed .

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