Background/Purpose: Anti-acetylated-peptide antibodies (AAPA) have been found in rheumatoid arthritis (RA) patients and may be additional markers for diagnosis, particularly in rheumatoid factor (RF)/ anti-citrullinated protein antibodies (ACPA) negative patients. Here we investigated whether the presence of AAPA may be useful for prediction of Tumor-Necrosis-Factor-inhibitor (TNFi) treatment response.

Methods: RA patients starting their first TNFi treatment were identified and tested for AAPA (by ELISA using two acetylated peptides derived from vimentin), RF (by nephelometry), and ACPA (by ELISA) at baseline. Based on logistic regression analysis, Odds Ratios (OR) including 95% confidence intervals (95% CI) for association with a 50% response of the Simplified disease activity index (SDAI50) and for reaching SDAI low disease activity (LDA) or remission at 6 months were calculated. We also performed longitudinal analysis by General Estimated Equation analyses (GEE) and Cox-regression.

Results: Among the 93 patients starting on a TNFi (85% female, mean disease duration: 7.7±7 years; mean SDAI: 20±13), 53% were positive for AAPA, 57% for ACPA and 61% for RF; 35.5% were triple positive, and 7.5% only for AAPA. There was a higher proportion of RF+ and ACPA+ patients in the AAPA+ group.

Presence of AAPA was associated with significantly higher rates of SDAI50 response (44% vs. 18%; OR 3.58 95%CI: 1,1-11.6; p=0.034) and LDA (72% vs. 48%; OR: 3.01; 1.05-8.64; p=0.041). Analogous analysis for RF or ACPA did not show such association either with achieving SDAI50 (RF: 35% vs. 30%; OR: 1.15; 0.39-3.39; p=0.796; ACPA: 38% vs. 25%; OR: 1.66; 0.532-5.21; p=0.282) or LDA (RF: 68% vs. 52%; OR: 2.08, 0.74-5.82; p=0.163; ACPA: 67% vs. 52%; OR: 2.17; 0.75-6.27; p=0.155).

AAPA+ patients showed significantly higher relative changes in SDAI (p=0.021), CDAI (p=0.025), DAS-ESR (p=0.022) and DAS-CRP (p=0.014) compared to AAPA- patients. Respective analyses for RF and ACPA were not significant for any of the indices.

Longitudinal analyses of the SDAI in patients on TNFi revealed significant difference in SDAI over time between AAPA+ vs. AAPA- patients (p=0.045); again, this was not seen in the analyzes of RF (p=0.597) or ACPA (p=407). Treatment retention was significantly higher for AAPA+ patients (Hazard Ratio, HR: 0.506; 0.310-0.829; p=0.007); this effect remained significant after adjustment for RF and ACPA (HR=0.556; 0.327-0.946; p=0.03; Figure). For RF or ACPA the crude HR were 0.689 (0.420-1.131; p=0.141) and 0.613 (0.376-1.000; p=0.050), respectively.

Conclusion:  Although validations in other cohorts are warranted for confirmation, in this observational cohort, AAPA positivity appeared to be good discriminator of response to the first TNFi-treatment and associated with more favorable long-term control of disease activity and treatment retention.