Background Anti-acetylated-peptide antibodies (AAPA) have recently been described in rheumatoid arthritis (RA) patients. Patients that show multiple autoantibody positivity have a higher likelihood to flare when stopping biological treatment. The role of AAPA antibodies for response to Tumor-Necrose-Factor-inhibitor treatment (TNFi) has not been explored.
Objectives To determine the prevalence and serological overlap of AAPA to rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) in a cohort of RA patients starting their TNF-inhibitor, and to assess their relation of autoantibody status to response to therapy.
Methods We measured AAPA by ELISA using two acetylated peptides derived from vimentin, as well as RF and ACPA. We evaluated the prevalence of autoantibodies, baseline characteristics of autoantibody positive and negative patients, and their association with a 50% response by the Simplified disease activity index (SDAI50), and with achieving of SDAI low disease activity or remission at 6 months after starting the first TNFi. Likelihood ratios were calculated from logistic regression analyses. To better determine differences in SDAI change over time General Estimated Equation analyses (GEE) was used.
Results Among our 93 patients starting treatment on a TNFi (85% female, mean disease duration: 7.7±7 years mean SDAI20±13), 50% were positive for AAPA, 57% for ACPA and 61% for RF (for overlap of antibodies see figure). There were no significant differences in baseline characteristics found between AAPA positive and negative patients. 61% of patients reached LDA or REM and 33% achieved an SDAI50 response after 6 months of TNFi treatment. AAPA positive patients showed a likelihood ratio (LR+) of 5.3 (p=0.022) to achieve an SDAI50 response and 3.9 (p=0.048) to reach LDA/REM. In contrast, being RF or ACPA positive did not coincide with a higher likelihood of achieving SDAI50 (LR+ of 0.08; p=0.773 and 1.09; p=0.297, respectively) or LDA/REM (LR+ of 1.83; p=0.177 and 1.55; p=0.213). Relative changes upon treatment with TNFi in composite scores were neither different between RF+ vs. RF- patients, nor between ACPA+ vs ACPA-patients; however AAPA+ showed significantly higher relative changes in SDAI (p=0.021), CDAI (p=0.025) and DAS (p=0.022) compared to AAPA- patients. Of note, relative changes in CRP were similar between the groups.
GEE on up to 230 days of TNFi treatment or until change of treatment, showed no significant difference in SDAI courses comparing RF+ vs RF- or ACPA+ vs ACPA- patients; but for AAPA+ vs. AAPA- patients the difference in change in SDAI was significant (p=0.045) over time.
Conclusions AAPA positivity, in contrast to RF and ACPA positivity, appears to have a tighter association with greater levels of response in patients who are initiating TNFi-treatment. Therefore, AAPA might add additional information to estimate the chances of RA patients for responding to TNF-inhibitors.
Juarez M, Bang H, Hammar F, et al. Identification of novel antiacetylated vimentin antibodies in patients with early inflammatory arthritis. Ann Rheum Dis 2016;75(6):1099–107.
Disclosure of Interest None declared