Background Anti-acetylated-peptide antibodies (AAPA) have recently been described in rheumatoid arthritis (RA) patients and may be used as a further diagnostic marker in patients with undifferentiated arthritis (1).

Objectives To determine the prevalence of AAPA in a cohort of RA patients starting their first conventional synthetic DMARD treatment (csDMARD). In addition, we aimed to evaluate the usefulness of AAPA as potential predictors of clinical response to methotrexate (MTX) therapy.

Methods We measured IgG and IgA AAPA by ELISA using two acetylated peptides derived from vimentin. We tested by regression, parametric and non-parametric analyses of disease activity measures if AAPA show potency for predicting response to MTX.

Results Among 110 patients starting treatment on MTX, 74.5% were positive for IgG and/or IgA AAPA: 49% were positive for either IgA or IgG antibodies and 25.5% were IgA/IgG double positive. In comparison, 63.6% of the patients were positive for either RF or ACPA (measured by the CCP assay). In the AAPA positive patients; in total, 26.4% of the patients showed IgA antibodies and 73.6% were positive for IgG AAPA. Importantly, of the 36.4% of patients negative for both RF and ACPA (double negative), 55% were positive for IgG and/or IgA AAPA, and the remaining 45% (i.e. 16% of the total cohort) were completely seronegative (triple-negative; see table). When comparing triple negative patients with the AAPA positive double-negative ones, no significant difference in baseline characteristics was found but a trend that patients with more seroreactivities showed higher composite disease activity scores. Analyzing the clinical response to MTX, AAPA positive double-negative patients showed a significantly greater relative SDAI change after 6 months compared to triple-negative patients (p=0.028; median (IQR): -44.6% (-58.5 - -28.90) vs. 5.26% (-23.9 - 55.5%). In addition, there was a significantly greater relative change in CRP and erythrocyte sedimentation rate in AAPA positive double-negative patients.

In a backward regression model only RF could significantly be associated with the SDAI response, leading to + 30% relative change in SDAI (p=0.024). Status of ACPA and AAPA as potential predictors had to be excluded. Furthermore, RF positive patients showed larger relative changes in CRP, ESR, SDAI, CDAI and DAS after 6 months of MTX treatment

Conclusions AAPA commonly occur in RA patients and were, in fact, the most prevalent autoantibodies in our cohort. Measuring AAPA in addition to RF and ACPA reduced the prevalence of seronegative patients by more than 50%. These AAPA positive but RF and ACPA negative patients responded significantly better to MTX. Therefore, AAPA positivity in RF and ACPA negative patients identifies a subgroup of patients with a more favourable response to MTX.

1. Juarez M, Bang H, Hammar f et al. Ann Rheum Dis 2015 Jul 9; Epub ahead of print.

Disclosure of Interest P. Studenic: None declared, S. Blüml: None declared, H. Bang Employee of: has developed the assay, M. Unger: None declared, K. Raza: None declared, D. Aletaha: None declared, J. Smolen: None declared, G. Steiner: None declared