gms | German Medical Science

Background: Anti-citrullinated protein antibodies (ACPAs) are markers of RA, and emerging evidence suggests a possible role in disease progression. Analysis of biomarkers from AMPLE provides a unique opportunity to probe the differential effects of treatment with biologic DMARDs with distinct mechanisms of action (MoA) [1]. We characterized changes in ACPA profiles over time and evaluated the relationship between ACPA and disease activity in patients treated with abatacept or adalimumab.

Methods: Patients were MTX failures and biologic-naïve [1]. Anti-CCP2+ status was determined using a commercial anti-CCP2 ELISA-established cut-off, performed at baseline. ACPA analysis included 20 specificities and was performed using a custom assay [2], measured at baseline, 85, 365 and 729 days. DAS28 (CRP) and ACPA changes were compared using an ANCOVA model with treatment as a factor; baseline values and DAS28 (CRP) strata were covariates. Comparisons of patients who achieved or failed to achieve a Major Clinical Response at Day 729 (MCR729) were also made.

Results: In patients with baseline serum measures available, 185/251 (74%) in the abatacept arm and 203/257 (79%) in the adalimumab arm were anti-CCP2+. For both treatments, baseline anti-CCP2+ patients showed greater improvements in DAS28 (CRP) and HAQ than baseline negative patients (Table 1 [Tab. 1]). Reductions in specific ACPAs were observed in both treatment arms over 2 years, independent of clinical response, although they followed different patterns (Figure 1 [Fig. 1]). Certain ACPAs had a greater mean reduction from baseline in abatacept- than adalimumab-treated patients, most notably ACPAs against apolipoprotein E and histones 2A and 2B during Year 2 of treatment. In patients with MCR729, abatacept produced a continued decline in median levels of most ACPAs beyond Year 1 of treatment (Figure 1 – left [Fig. 1]). Median levels of most ACPAs rebounded after Year 1 in adalimumab-treated patients who reached MCR729 (Figure1 – right [Fig. 1]).

Conclusion: AMPLE provided an opportunity to evaluate the molecular differences in RA pathology altered by treatment with two biologics with distinct MoA. Both agents resulted in a greater response in anti-CCP2+ patients and impacted the overall pattern of ACPA fine specificities. Among patients with similar sustained clinical response, abatacept and adalimumab induced different impacts on ACPA over time, suggesting different effects on adaptive immunity [3].