Background Autoantibody production, including RF and anti-citrullinated protein antibody (ACPA), may play a role in RA disease pathogenesis.1 ACPA positivity(+) in patients (pts) with RA is a strong predictor of joint erosions and radiographic progression.1,2 However, data evaluating the association of seropositive, erosive disease with disease activity and resource use (RU) are limited.
Objectives To evaluate the association of ACPA+/RF+ with erosions and disease activity; to compare activity, RU and work productivity (WP) in ACPA+ pts with erosions vs all other RA pts.
Methods Pts enrolled in the BRASS Registry were analysed. BRASS comprises mostly pts with established RA who were evaluated annually on clinical measures and semi-annually on clinical pt-reported outcomes and resource utilization parameters. Baseline (BL) visit was the time of enrolment into BRASS. ACPA levels at BL and annual follow-up were measured using a validated ELISA (Inova Diagnostics, San Diego, CA) until its discontinuation in 2011, and the Euro-Diagnostica assay (IBL-America, Minneapolis, MN) thereafter. RF levels at BL and follow-up were measured during the annual rheumatologist visit. RU and WP were measured at 6 months (M) via pt questionnaires. Subgroups at BL were described using Wilcoxon rank-sum test (continuous variables) and Pearson's chi-square test (categorical variables); multivariate logistic regression models (binary outcome variables) and ordinary least-square regression analysis (continuous outcome variables) were used. Covariates included in the multivariate models were age, sex, race, BMI, RA duration, number of co-morbidities and treatment.
Results Among 1309 pts with ACPA data, 82% were female, mean (SD) age was 56.5 (14.1) yrs and DAS28(CRP) was 3.7 (1.6). Pts had mean (SD) TJC of 14.3 (14.0), ACPA levels of 128.3 (151.9) units/mL and RF levels of 127.7 (301.6) units/mL. After controlling for covariates, odds ratio (OR) for erosive disease was 2.72 (95% CI: 1.77, 4.18) for ACPA+ and 1.36 (0.88, 2.08) for RF+ (Fig. 1a). The OR for attaining SDAI LDA (<3.3) was 0.37 (0.21, 0.66) for ACPA+ and 1.45 (0.82, 2.56) for RF+ (Fig. 1b). ACPA titres were associated with erosive disease: 61 vs 32% of pts had erosive disease in the high vs low ACPA quartiles. ACPA+ pts with erosions (n=498) had higher mean SDAI (28.0 vs 18.1) and joint counts (19.2 vs 11.1), and greater proportions (60 vs 38%) were treated with biologic (b)DMARDs compared with all other RA pts. In multivariate analyses, the OR for SDAI remission in ACPA+ pts with erosions was 0.19 (0.10, 0.37); a significantly (p<0.05) greater proportion of these pts had durable equipment use (30.6 vs 22.1%) and all-cause hospitalizations (20.1 vs 13.1%) compared with all other RA pts at 12M. This group also had lower employment (38.7 vs 53.5%) and higher long-term disability (25.4 vs 17.3%) and retirement (32.5 vs 22.1%).
Conclusions ACPA+ has a stronger association with erosions and disease activity. The presence of ACPA+ and erosions (vs absence) is associated with higher disease activity, lower odds of remission and lower WP, even when treated with standard-of-care bDMARDs.
Aggarwal R, et al. Arthritis Rheum 2009;61:1472–83.
Jilani AA and Mackworth-Young CG. Int J Rheumatol 2015;2015:72810. doi: 10.1155/2015/728610.
Disclosure of Interest E. Alemao Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, Z. Guo Shareholder of: Bristol-Myers Squibb, Employee of: Bristol-Myers Squibb, C. Iannaccone: None declared, M. Frits: None declared, N. Shadick Grant/research support from: Bristol-Myers Squibb, Crescendo Biosciences, Amgen, UCB, Questcor, M. Weinblatt Grant/research support from: Bristol-Myers Squibb, Crescendo Bioscience, UCB, Amgen, Consultant for: Bristol-Myers Squibb, Crescendo Bioscience, UCB, AbbVie, Roche, Janssen, Pfizer, Lilly, Amgen